bromochloroacetic-acid and Ovarian-Neoplasms

Cellular fibromas represent ~10% of ovarian fibromas. Mitotically active cellular fibromas show mild nuclear atypia but ≥4 mitoses/10 high-power fields: the clinical course is usually uneventful but literature review is lacking. A 34-yr-old woman underwent left oophorectomy for a 9-cm ovarian mitotically active cellular fibroma at another hospital. The tumor was cellular (spindle cells in fascicular and storiform patterns) revealing mild atypia and 4 nonatypical mitoses/10 high-power fields without necrotic areas. After 16 yr, the tumor recurred as a 5-cm peritoneal nodule on the anterior sigmoid wall near the sigmoid-rectal junction. Frozen section revealed a spindle cell tumor invading the intestinal tunica muscularis propria: a gastrointestinal stromal tumor was favored as previous history was unavailable at that time. Intestinal resection was performed: no residual tumor was found. The patient was followed-up for 8 yr without further recurrences. The peritoneal nodule showed 2 mitoses/10 high-power fields and pericellular reticulin staining. The tumor was variably positive for vimentin/bcl-2/melan-A/CD56/ER/PR/α-inhibin/CD10/calretinin, focally positive for desmin, negative for pan-cytokeratin/actin/EMA/CD34/HMB45/CD117/CD99/S100/synaptophysin. The Ki67-index was ~9%. To our systematic literature review, 7 additional recurrent cases were reported. We describe a mitotically active cellular fibroma recurring after the longest interval of time. Extensive sampling of difficult cases should exclude malignant areas. Moderate nuclear atypia, tumor rupture, adhesions to pelvic/abdominal organs, infarction with extraovarian involvement, and incomplete excision may lead to relapse but there are conflicting data: prolonged follow-up can be suggested in these cases.

Topics: Adult; Biomarkers, Tumor; Diagnosis, Differential; Female; Fibroma; Humans; Inhibins; Keratins; Neoplasm Recurrence, Local; Ovarian Neoplasms; Ovary; Synaptophysin; Vimentin

To present the clinicopathologic features of two cases of luteinized thecomas with sclerosing peritonitis (LTSP), characterize the cellular proliferation in the sclerosing peritonitis (SP), and review the literature.. The clinical, laboratory, and imaging data, operative findings, and pathology materials were reviewed and summarized. Samples of the SP were stained with keratin AE1/AE3, vimentin, CD34, calretinin, smooth muscle actin, ER/PR, CD10 and desmin. A literature search was performed to identify cases of LTSP for comparison.. A total of 43 cases of LTSP syndrome were identified. Frequent clinical features included ascites (74%), abdominal pain (35%), bowel obstruction (42%), and bilateral masses (84%). We isolated a distinct form of ovarian luteinized thecoma (thecomatosis) and peculiar sclerosing peritonitis (SP). IHC analysis shows a proliferation of specialized (vimentin+/keratin+/CD34+) submesothelial fibroblasts (SMF) with patchy expression of calretinin and hormone receptors.. LTSP syndrome is a rare entity presenting with abdominal pain, bowel obstruction, ascites, ovarian masses, and SP containing specialized (vimentin+/keratin+/CD34+) SMF. LTSP must be distinguished from abdominal cocoon, isolated SP, Meigs' syndrome, and peritoneal carcinomatosis. The importance of recognizing the diagnosis is stressed, as failure to manage this disease conservatively leads to significant morbidity and mortality. The SP and bowel obstruction may persist for months, even after resection of the tumours, resulting in extended medical therapy. Based on the immunophenotype of the peritoneal lesions, strategies to elucidate 'targeted' pharmacologic agents that could inhibit the proliferation of specialized (vimentin+/keratin+/CD34+) SMF may be of benefit.

Topics: Adult; Antigens, CD34; Antineoplastic Agents; Carcinoma; Disease Management; Female; Fibroblasts; Humans; Intestinal Obstruction; Keratins; Meigs Syndrome; Middle Aged; Ovarian Neoplasms; Ovariectomy; Peritoneal Fibrosis; Peritoneal Neoplasms; Thecoma; Treatment Outcome; Vimentin

Ovarian pulmonary-type small cell carcinoma is a rare and extremely aggressive neoplasm. We report the occurrence of an ovarian small cell carcinoma of pulmonary type in a 54-year-old woman. She underwent a total abdominal hysterectomy with a bilateral salpingo-oophorectomy and infracolic omentectomy. A diagnosis of stage IIIA pulmonary-type small cell carcinoma was rendered. The tumor appeared to be composed of a solid growth of small cells arranged in sheets and closely packed nests with insular arrangements separated by a fibrous stroma. The tumor cells had hyperchromatic nuclei with inconspicuous nucleoli and scanty cytoplasm. Rosette and rosette-like structures were scattered. Immunohistochemical staining showed positivity for synaptophysin, neural cell adhesion molecule (NCAM), and focally for chromogranin. Cytokeratin and neuron-specific enolase (NSE) were also positive. Over 80% of the tumor cells showed strong reactivity for MIB-1. Electron microscopy showed neuroendocrine granules. She was effectively treated with paclitaxel plus carboplatin after the surgery.

Topics: Antineoplastic Agents; Carboplatin; Carcinoma, Neuroendocrine; Carcinoma, Ovarian Epithelial; Carcinoma, Small Cell; Carrier Proteins; Female; Humans; Keratins; Lung; Middle Aged; Neoplasms, Glandular and Epithelial; Neural Cell Adhesion Molecules; Ovarian Neoplasms; Paclitaxel; Tomography, X-Ray Computed; Ubiquitin-Protein Ligases

The gynandroblastoma is an extremely rare sexual cord stromal tumor, which contains both male and female elements, characterized by Sertoli or Leydig cells and granulose cells. We describe an ovarian gynandroblastoma in a 28 year-old female patient, found accidentally during a cesarean section operation. There is only one reported case in world literature occurring in a pregnant woman. The principal component we found was adult granulose cells, with a microfollicular pattern, and the presence of luteinized cells in some areas; besides we found the presence of well differentiated Sertoli cells elements, in addition to Leydig cells groups, in over 10% of the tumoral surface. Inmunohistochemical stainings were performed: citokeratin, which resulted positive in Sertoli cells and negative in granulose cells; and inhibin, which was positive in both components showing its mixed origin.

Topics: Adult; Biomarkers, Tumor; Cesarean Section; Female; Granulosa Cells; Humans; Incidental Findings; Inhibins; Keratins; Leydig Cells; Male; Neoplasm Proteins; Ovarian Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Sertoli Cells; Sex Cord-Gonadal Stromal Tumors

Breast metastases from gastric cancer are extremely rare. A case report of a 37-year-old female with breast inflammatory invasion and ascites is described. Breast biopsy revealed carcinomatous invasion of the lymphatics from adenocarcinoma cells with signet-ring features. Estrogen (ER) and progesterone receptors (PR) and c-erb-B2 were negative. Upper gastrointestinal endoscopy revealed a prepyloric ulcerative mass. Histopathologic examination of the lesion showed infiltration from a high-grade adenocarcinoma, identical with that of the breast. Immunostaining was positive for cytokeratins CK-7 and CK-20 and CEA and negative for ER and PR. Ascitic fluid cytology was positive for adenocarcinoma cells. Mammography was not diagnostic. Abdominal CT scanning revealed large ovarian masses suggestive of metastases (Krukenberg's tumor). A cisplatin-based regimen was given but no objective response was observed. The patient died six months after initial diagnosis. A review of the literature is performed.

Topics: Adenocarcinoma; Adult; Ascites; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms

The differential diagnosis of ovarian carcinomas, including secondary tumors, remains a challenging task. Mucinous carcinomas of the ovary are rare and can be easily confused with metastatic mucinous carcinomas that may present clinically as a primary ovarian tumor. Most of these originate in the gastrointestinal tract and pancreas. International Federation of Gynecology and Obstetrics (FIGO) stage is the single most important prognostic factor, and stage I carcinomas have an excellent prognosis; FIGO stage is largely related to the histologic features of the ovarian tumors. Infiltrative stromal invasion proved to be biologically more aggressive than expansile invasion. Metastatic colon cancer is frequent and often simulates ovarian endometrioid adenocarcinoma. Although immunostains for cytokeratins 7 and 20 can be helpful in the differential diagnosis, they should always be interpreted in the light of all clinical information. Occasionally, endometrioid carcinomas may exhibit a microglandular pattern simulating sex cord-stromal tumors. However, typical endometrioid glands, squamous differentiation, or an adenofibroma component are each present in 75% of these tumors whereas immunostains for calretinin and alpha-inhibin are negative. Endometrioid carcinoma of the ovary is associated in 15-20% of the cases with carcinoma of the endometrium. Most of these tumors have a favorable outcome and they most likely represent independent primary carcinomas arising as a result of a Mullerian field effect. Although the criteria for distinguishing metastatic from independent primary carcinomas rely mainly upon conventional clinicopathologic findings, loss of heterozygosity and gene mutation analyses can be helpful. Transitional cell carcinomas are distinguished from undifferentiated carcinomas by the presence of thick, undulating papillae with smooth luminal borders, microspaces, and tumor cells with distinctive 'urothelial' appearance. Krukenberg tumors are metastatic adenocarcinomas traditionally perceived as composed of mucin-filled signet-ring cells associated with a striking proliferation of the ovarian stroma but many variations on this pattern occur.

Topics: Base Sequence; beta Catenin; Colonic Neoplasms; Cytoskeletal Proteins; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mutation; Ovarian Neoplasms; Prognosis; ras Proteins; Trans-Activators

Immunohistochemistry has become an important tool in the diagnosis of ovarian tumors. This article reviews the role of immunohistochemistry in the differential diagnosis of the three main categories of ovarian tumors, with emphasis on recently developed antibodies. In the surface epithelial stromal category the most common problem is its discernment from metastasis. The use of differential cytokeratins, primarily CK7 and CK20, as well as Cdx-2, beta-catenin, and P504S in differentiating between metastatic adenocarcinoma, particularly of colorectal origin, and primary ovarian carcinoma is discussed. Dpc4 may be useful in distinguishing pancreatic from ovarian mucinous carcinomas, because up to 55% of pancreatic carcinomas lack Dpc4 expression, whereas the differential expression of mucin genes may be helpful in distinguishing between primary ovarian mucinous and metastatic tumors. Urothelial markers (thrombomodulin and uroplakin III) and renal cell carcinoma markers (CD10 and renal cell carcinoma marker) can be helpful in the diagnosis of metastatic urothelial and renal cell tumors to the ovary. The roles of inhibin, calretinin, CD99, and other recently described markers in the diagnosis of sex cord-stromal tumors are reviewed. The uses of OCT-4 (POU5F1) (a new highly sensitive and specific marker of dysgerminoma and embryonal carcinoma), CD30, and c-kit are also discussed.

Topics: Biomarkers, Tumor; CA-125 Antigen; Carcinoma; Diagnosis, Differential; Female; Germinoma; Humans; Immunohistochemistry; Keratins; Neoplasm Metastasis; Ovarian Neoplasms; Racemases and Epimerases; Sex Cord-Gonadal Stromal Tumors; Trans-Activators

Gonadal germ cell tumors continue to be the cause of diverse, diagnostically challenging issues for the pathologist, and their correct resolution often has major important therapeutic and prognostic implications. They are academically interesting because of the biological diversity exhibited in the two gonads and variation in frequency of certain neoplasms. The most dramatic examples of the latter are the frequency of dermoid cyst in the ovary compared to the testis and the reverse pertaining to embryonal carcinoma. Within the teratoma group, there is strong evidence that ovarian and prepubertal testicular teratomas are derived from benign germ cells, a pathogenesis that likely applies also to the rare dermoid cysts and uncommon epidermoid cysts of the testis. In contrast, postpubertal testicular teratomas derive from malignant germ cells, specifically representing differentiation within a preexistent nonteratomatous cancer. As expected, given the foregoing, teratomas in boys are clinically benign, whereas in postpubertal males they are malignant, independent of their degree of immaturity. On the other hand, immaturity is an important finding in ovarian teratomas, irrespective of age, although its significance in children has recently been challenged. It is usually recognized on the basis of embryonic-appearing neuroepithelium, which shows mitotic activity and apoptosis in contrast to differentiated neuroepithelial tissues, which may occur in mature ovarian teratomas. Rarely it is based on the presence of cellular, mitotically active glial tissue. Fetal-type tissues alone are not sufficient for a diagnosis of immature teratoma. Further differences between the teratomatous tumors in the two gonads are the relative frequency of monodermal teratomas in the ovary in contrast to the testis, where only one subset, carcinoids, is seen with any frequency. When uncommon somatic-type malignancies (usually squamous cell carcinoma) occur in mature cystic teratomas of the ovary, this is a de novo form of malignant transformation; similar tumors in the testis, a very rare event, represent overgrowth of teratomatous elements that originated from malignant, nonteratomatous germ cell tumors and, therefore, had previously undergone malignant transformation. Germinomas may have several unusual features in each gonad; these include microcystic arrangements that suggest yolk sac tumor, tubular patterns that mimic Sertoli cell tumor, apparent increased cytological atypia that

Topics: Diagnosis, Differential; Female; Germinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-1 Antigen; Male; Neoplasms, Germ Cell and Embryonal; Organic Cation Transport Proteins; Ovarian Neoplasms; Proto-Oncogene Proteins c-kit; Teratoma; Testicular Neoplasms

The ovary is a common site of metastatic tumour. In many cases of ovarian metastasis there is a known history of malignancy but in other cases the ovarian tumour is the first manifestation of disease. In this review metastatic colorectal, appendiceal, gastric, breast, pancreatic and biliary tract, hepatocellular, renal, transitional and cervical carcinomas and metastatic malignant melanoma involving the ovary are discussed, as is the issue of synchronous ovarian and endometrial carcinomas. Peritoneal tumours, including primary peritoneal carcinoma, mesothelioma and intra-abdominal desmoplastic small round cell tumour, involving the ovary are also discussed, together with a variety of other rare, metastatic ovarian neoplasms. Many metastatic adenocarcinomas involving the ovary, especially those exhibiting mucinous differentiation, closely mimic primary ovarian adenocarcinomas with morphologically bland areas simulating benign and borderline cystadenoma. This is referred to as a maturation phenomenon. In recent years immunohistochemistry, especially but not exclusively differential cytokeratin (CK7 and CK20) staining, has been widely used as an aid to distinguish between a primary and secondary ovarian adenocarcinoma. While immunohistochemistry undoubtedly has a valuable role to play and is paramount in diagnosis in some cases, the results must be interepreted with caution, especially in mucinous tumours, and within the relevant clinical context. We feel the significance of differential cytokeratin staining is not always understood by histopathologists and this can result in erroneous interpretation. We critically discuss the value of immunohistochemistry and associated pitfalls with each tumour type described.

Topics: Adenocarcinoma; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Ovary

Ovarian metastasis originating from bronchioloalveolar carcinoma (BAC) has not been reported previously. We report a 63-year-old Chinese woman who was diagnosed as BAC with pleural metastasis in 1997. Four years later, she complained of vaginal bleeding, and a pelvic mass was discovered by an abdominal computerized tomography scan. Tumor debulking and total hysterectomy with bilateral salpingo-oopherectomy were performed. Pathology disclosed well-differentiated adenocarcinoma, with abundant clear cytoplasm, in the ovaries. Furthermore, immunohistochemical staining revealed that the tumor cells from the ovary and pleura were reactive to thyroid transcription factor 1 (TTF-1) and cytokeratin-7 (CK-7) but were negative for cytokeratin-20 (CK-20). The results of immunohistochemical staining, clinical course, and pathological features were compatible with the diagnosis of BAC with ovarian metastasis. In conclusion, to investigate the primary site of a metastatic ovarian cancer, clinicians should not forget the lungs since the incidence of lung cancer in females is increasing. Moreover, a monoclonal antibody panel for TTF-1, CK-7, and CK-20 may facilitate discrimination between primary and metastasized ovarian adenocarcinomas and/or identifying tumors of pulmonary origin.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Biomarkers, Tumor; Fallopian Tubes; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Middle Aged; Nuclear Proteins; Ovarian Neoplasms; Ovariectomy; Thyroid Nuclear Factor 1; Transcription Factors

A uterine tumor resembling an ovarian sex-cord tumor (UTROSCT) is a very rare lesion with only 38 cases reported in the literature so far. Here, we show an additional case of a pure UTROSCT with a DNA stemline at 1c in a 49-year-old woman presenting with abnormal vaginal bleeding. Problems in differential diagnosis arise mainly due to the variable histological picture of UTROSCT. Immunohistochemically, these tumors express cytokeratin, epithelial membrane antigen, vimentin, and smooth muscle actin. Moreover, in some cases, CD99 and alpha-inhibin are detectable. Although 36% of UTROSCT have infiltrative margins, almost all of them behave benignly. It is thus questionable whether the same prognostic criteria apply for these tumors as for endometrial stromal sarcomas. However, in the so-called mixed UTROSCT, the endometrial stromal sarcoma component determines the outcome.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Cell Nucleus; DNA, Neoplasm; Female; Humans; Image Cytometry; Immunohistochemistry; Keratins; Middle Aged; Ovarian Neoplasms; Ploidies; Sex Cord-Gonadal Stromal Tumors; Treatment Outcome; Uterine Neoplasms; Vimentin

Topics: Bone Marrow; Bone Marrow Examination; Bone Marrow Neoplasms; Breast Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphatic Metastasis; Neoplastic Cells, Circulating; Ovarian Neoplasms; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Stomach Neoplasms; Uterine Cervical Neoplasms

To evaluate the histologic features and biologic behavior of unclassified sex cord-stromal tumors.. The eight patients' ages at presentation ranged from 14 to 83 years. Presenting symptoms and physical findings included abdominal pain, abnormal uterine bleeding, ascites, and abdominal and pelvic masses. One patient also had bilateral sex cord tumors with annual tubules and probable Peutz-Jeghers syndrome.. The tumors ranged from 4 to 27 cm in diameter and were described as partially encapsulated, solid, and cystic. Histologically, the tumors were composed of diffuse proliferations of sex cord cells, with cords, tubules, and follicle-like structures. The stromal cells were spindle-shaped, with scanty cytoplasm. The neoplasms were vimentin-positive and, sometimes, cytokeratin CAM 5.2- and AE1/3-positive and epithelial membrane antigen-negative. Six patients were disease-free from 2 months to 6 years after operation. One patient was lost to follow-up. The patient with probable Peutz-Jeghers syndrome had a tumor with unusual morphology and died of the neoplasm 4 years after the diagnosis. Three of 32 other cases with clinical follow-up mentioned in the pathology literature have been associated with a malignant behavior.. The biologic behavior of unclassified sex cord-stromal tumors resembles that of Sertoli-Leydig cell tumors of intermediate differentiation rather than poorly differentiated tumors, which might have been expected in view of the lack of specific differentiation. This finding is important with regard to postoperative management.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Keratins; Microscopy, Electron; Ovarian Neoplasms; Ovary; Prognosis; Sex Cord-Gonadal Stromal Tumors; Vimentin; World Health Organization

A rare case of ovarian mucinous cystadenocarcinoma with sarcoma-like mural nodules is reported. Macroscopically, nodular or granular lesions were scattered over the inner surface of a huge, multilocular tumor in the left ovary. The histopathological features were consistent with those of previously documented cases, except significant squamous metaplasia in the present case. The pleomorphic sarcoma-like cells showed a positive reaction for vimentin and alpha-antichymotrypsin but were negative for carcinoembryonic antigen and common epithelial membrane antigen by immunohistochemistry. Electron microscopically, the tumor cells had neither desmosomes nor secretory granules, but they possessed abundant intermediate filaments. Both immunostaining and ultrastructure suggested that the sarcoma-like nodules were derived from reactive proliferation of fibrohistiocytic cells. The fibrohistiocytic reaction seemed to occur in response to hemorrhage, because hemorrhage was reported to be associated with the mural nodules in most of the previous cases as well as ours.

Topics: Cystadenocarcinoma, Mucinous; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Middle Aged; Ovarian Neoplasms; Sarcoma

Desmoplastic small cell tumor (DSCT) is a recently described intraabdominal neoplasm of uncertain histogenesis that occurs predominantly in boys and young men. We report a case in a young woman that presented clinically as bilateral ovarian tumors with extensive pelvic and abdominal dissemination. The patient had cytoreductive surgery followed by combination chemotherapy. She had a complete clinical remission, but tumor recurrence was detected 1 year after diagnosis and the patient died of her disease 18 months after presentation. DSCT has a distinctive histologic appearance and a unique immunophenotype. It can present as an ovarian neoplasm and must be considered in the differential diagnosis of small cell tumors of the ovary.

Topics: Adult; Desmin; Fatal Outcome; Female; Humans; Keratins; Neoplasm Metastasis; Ovarian Neoplasms; Pregnancy

Small cell carcinoma of the ovary is a rare histological form which is highly malignant. We have decided to consider this as an epithelial tumour after studying it with the optical and the electron microscope. It is however difficult to put it in to a definite type because it is highly undifferentiated. On the clinical level small cell carcinoma is different from other ovarian cancers in several respects. Whereas ovarian tumours usually tend to occur in menopausal women in the fifth or sixth decade of life, small cell carcinomas of the ovary occur mainly in younger women of ages between 10 and 38 years. Furthermore, women who are attacked by this kind of a carcinoma tend to die very soon after the diagnosis has been made without receiving any benefit from the many therapies that have been tried to improve the prognosis. We have studied the condition after seeing two cases of small cell carcinoma in the University Gynaecological Department of Tours, and we have made a study of the literature. We have studied the therapeutic angle for these tumours and we have tried to find out what the best technique will be to cope with this awful prognosis. We discuss whether it might be worthwhile in future to intensify therapy in combination with bone marrow autotransplantation.

Topics: Adult; Antigens, Neoplasm; Carcinoma, Small Cell; Combined Modality Therapy; Female; Humans; Keratins; Membrane Glycoproteins; Mucin-1; Neoplasm Staging; Ovarian Neoplasms; Prognosis

This is an immunohistochemical and ultrastructural study of two small cell carcinomas of the ovary with a review of the literature. These cases showed a dimorphic population of small and large cells sharply demarcated from each other. Cytokeratin 18 and vimentin were mainly expressed in the large tumour cells, some of which also stained for alpha-smooth muscle actin. Periodic-acid-Schiff-positive, alpha-1-antitrypsin-positive hyaline globules were present in one case. Ultrastructural findings included filamentous nucleolonema as well as evidence of smooth muscle differentiation. Some of these observations have not been previously reported. Certain of the above features seem to support a germ cell origin of small cell carcinoma, but they cannot be considered specific for germ cell neoplasms. Thus, small cell carcinoma of the ovary cannot be classified into one of the known categories of ovarian tumours at the present time.

Topics: Actins; Adult; alpha 1-Antitrypsin; Carcinoma, Small Cell; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Vimentin

A case of mucinous cystic ovarian tumor with mural nodules of anaplastic carcinoma in a 30-year-old woman is described. The carcinomatous components within the nodules showed strong immunopositivity for cytokeratin and carcinoembryonic antigen, and ultrastructurally they displayed epithelial and glandular differentiation. Omental metastasis had already developed in the patient, and she received postoperative adjuvant chemotherapy consisting of cyclophosphamide and cis-platinum. No sign of recurrence was evident 4 months after the operation. The literature is reviewed and the importance of adjuvant chemotherapy in the postoperative management of such patients highlighted. The salient pathologic features differentiating mural nodules of anaplastic carcinoma and true sarcoma from prognostically favorable sarcoma-like nodules are presented.

Topics: Adenocarcinoma, Mucinous; Adult; Anaplasia; Carcinoembryonic Antigen; Cell Membrane; Cytoplasm; Female; Humans; Keratins; Ovarian Neoplasms

A rare case of adenomatoid tumor arising in the ovary is presented. At autopsy on a 61-year-old woman, a soft, solid and cystic tumor, measuring 0.8 X 0.7 cm, was detected in the hilus of the left ovary. Light microscopic study showed characteristic features of adenomatoid tumor. Alcian blue stain, with and without hyaluronidase pretreatment, revealed the presence of hyaluronic acid on the luminal surface and in the vacuoles of the tumor cells. Immunohistochemical stains of tumor cells were positive for low-molecular-weight cytokeratin (PKKL), vimentin, and carbohydrate antigen (CA) 125, whereas they were focally positive for high-molecular-weight cytokeratin (34 beta E12). They were negative for factor VIII-related antigen (FVIII-RAG), Ulex europaeus I lectin (UEA I), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Ultrastructural studies disclosed surface microvilli and bundles of tonofilaments. These observations strongly support the idea of this tumor being of mesothelial origin.

Topics: Cytoplasm; Female; Humans; Immunohistochemistry; Keratins; Mesothelioma; Microvilli; Middle Aged; Ovarian Neoplasms; Staining and Labeling

A wide variety of human neoplasms were examined by immunocytochemical and ultrastructural techniques. In most, one intermediate filament (IF) type was expressed reflecting the tissue of origin. However, multiple classes of intermediate filaments were regularly found in a subgroup of these tumors. We chose to subdivide them into those with a complex or mixed growth pattern, and those which showed a more "monomorphic" histologic growth pattern. This latter group is the subject of this paper. Regular coexpression of cytokeratin and vimentin was observed in tumors of endometrial, thyroid, ovarian and renal origin, and coexpression of cytokeratin and neurofilament was observed in a subgroup of neuroendocrine tumors. Immunocytochemical/ultrastructural correlation demonstrated few, if any, observable intermediate filaments in tumors expressing only low molecular weight cytokeratin, whereas vimentin and neural filament characteristically were randomly dispersed or formed whorled bundles of cytoplasmic filaments. The potential diagnostic usefulness of these observations in surgical pathology is discussed.

Topics: Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Cytoskeleton; Endocrine System Diseases; Female; Humans; Intermediate Filaments; Keratins; Kidney Neoplasms; Lung Neoplasms; Ovarian Neoplasms; Thyroid Neoplasms; Uterine Neoplasms; Vimentin

Keratin granulomas in the peritoneum are a rare finding with multiple etiologies and can be especially challenging for both the pathologist and the surgeon when these lesions are grossly visible. We report a case of a unique frozen section diagnostic scenario of evaluation of keratin granulomas in the peritoneum of a 47-year-old woman in the setting of multiple potential culprits: endometrial endometrioid adenocarcinoma following fertility sparing treatment, and a concurrent dermoid cyst. We discuss the various etiologies of keratin granulomas in the peritoneum, mechanism of their formation, diagnostic significance, as well as implications of fertility sparing treatments. To the best of our knowledge, this is the only case of keratin granulomas in the peritoneum with multiple distinct potential pathologic culprits as well the only case following fertility sparing treatment.

Topics: Biomarkers; Carcinoma, Endometrioid; Dermoid Cyst; Diagnosis, Differential; Endometrial Neoplasms; Female; Frozen Sections; Granuloma; Humans; Keratins; Middle Aged; Ovarian Neoplasms; Peritoneal Diseases

Ovarian clear cell carcinoma (OCCC) accounts for approximately 18% of all epithelial ovarian malignancies in Taiwan and portends a poor prognosis. Here, we sought to investigate whether immunohistochemistry with an anti-pan-cytokeratin antibody cocktail (AE1/AE3) can be used as an adjunct to hematoxylin and eosin (H&E) staining for improving the detection of isolated tumor cells (ITCs) and micrometastasis to pelvic lymph nodes (LNs). We also assessed whether these lesions may predict disease recurrence.. Pelvic lymphadenectomy specimens were obtained from 197 patients with stage 1 OCCC who had undergone surgery between 2000 and 2018 from Linkou and Kaohsiung Chang Gung Memorial Hospital. Immunohistochemical staining with AE1/AE3 was applied to a total of 1186 slides. Clusters of metastatic tumor cells, detected immunohistochemically, were classified as ITCs (clusters with diameters of ≤0.2 mm) or micrometastases (tumor cell clusters of >0.2 but ≤2.0 mm). We also assessed the diameter of metastases in patients with positive lymph nodes (stage IIIA1, n = 3, 7 positive nodes).. Clusters with a positive AE1/AE3 staining were identified in five (2.53%) of the 197 patients (ITCs, n = 3; micrometastasis, n = 2). Four patients had no evidence of disease recurrence but a patient recurred at follow-up. Metastatic foci of patients with stage IIIA1 disease were all >2.0 mm in size.. Immunohistochemical staining with AE1/AE3 can identify micrometastasis or ITCs in LNs missed on routine H&E staining. The role of micrometastasis in predicting recurrent OCCC and implementing on treatment strategies requires further investigation.

Topics: Adenocarcinoma, Clear Cell; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Micrometastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Prognosis

A new method of double immunofluorescent staining for flow cytometry has been created to evaluate quantitative expression of mesenchymal protein vimentin only in epithelial cells of a solid tumor that is a mix of different origin cells.

Topics: Biomarkers, Tumor; Epithelial-Mesenchymal Transition; Female; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Keratins; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Progression-Free Survival; Proportional Hazards Models; Single-Cell Analysis

In 2014 World Health Organization criteria, seromucinous carcinoma was defined as a new histological subtype in ovarian carcinomas, but "seromucinous carcinoma" was not defined in endometrial carcinomas. The aim of this study was to identify seromucinous carcinoma resembling ovarian seromucinous carcinoma in endometrial carcinomas, and to evaluate the clinical significance for prognoses of the patients.. Central pathological review was conducted for patients with endometrioid carcinoma of the endometrium treated by primary surgery at our hospital between 1990 and 2013.. Among 340 cases included in the study, no case had all tumor cells resembling ovarian seromucinous carcinoma in all specimens, and 31 cases (9.1%) had seromucinous component in combination with endometrioid carcinomas. Immunohistochemical analysis revealed seromucinous component had positive reactivity for cytokeratin (CK) 7, and negative reactivity for CK20 and caudal type homeobox 2 (CDX2) in all cases. Seromucinous component showed lower immunoreactivity of estrogen receptor and progesterone receptor, compared with endometrioid carcinoma component. Progression-free survival of the cases with seromucinous component was better than those without seromucinous component (p=0.049).. Seromucinous component was identified in approximately 10% of endometrioid carcinoma, and could be a histological predictor for prognosis.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Endometrioid; CDX2 Transcription Factor; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Keratin-20; Keratins; Middle Aged; Ovarian Neoplasms; Prognosis; Receptors, Estrogen; Receptors, Progesterone

This descriptive study was carried out at Pathology Department, Shifa International Hospital from 2007 to 2016; all sex cord stromal tumours diagnosed during this time period were included. Epithelial, germ cell and metastatic tumours were excluded from the study. A total of 1254 Ovarian tumours were brought to Shifa of which47 (4%) were labeled as sex cord stromal tumours. Of these 36( 76 %)were granulosa cell tumour (adult33, juvenile3), 7 were labeled as sertoli leydig cell tumours (15%), 3 as thecoma/ fibroma group (7%)and only one case was labeled as microcystic stromal tumour of the ovary (2%). Overall age range for sex cord stromal tumours was 42 (12-71). Immunohistochemistry was done in 41 out of 47 cases. Sex cord stromal tumours of the ovary are rare tumours comprising 4% of the total. Adult Granulosa cell tumour is the commonest tumour seen in our study.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Calbindin 2; Child; Female; Granulosa Cell Tumor; Humans; Inhibins; Keratins; Middle Aged; Ovarian Neoplasms; Pakistan; Sertoli-Leydig Cell Tumor; Sex Cord-Gonadal Stromal Tumors; Thecoma; Young Adult

Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors.. A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody.. Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis.. The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.

Topics: Adenocarcinoma, Mucinous; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; CA-125 Antigen; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Lymphatic Vessels; Membrane Glycoproteins; Membrane Proteins; Middle Aged; Mucins; Ovarian Neoplasms; Reference Values; Tissue Array Analysis; Tumor Burden; Young Adult

Topics: Calbindin 2; Carcinoma, Small Cell; Female; Humans; Hypercalcemia; Keratins; Ovarian Neoplasms; S100 Calcium Binding Protein G; Young Adult

Topics: Adult; Breast Neoplasms; Carcinoid Tumor; Carcinoma, Adenoid Cystic; Carcinoma, Lobular; Chromogranin A; Diagnosis, Differential; Female; Humans; Hysterectomy; Keratins; Neoplasms, Multiple Primary; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors; Synaptophysin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Prolonged fixation of cells and tissues in 10% neutral buffered formalin (NBF) may decrease immunorecognition in some antigen-antibody pairs. Short fixation in 10% NBF followed by transfer to 70% ethanol has been used to overcome these effects, but the effects of this transfer on immunorecognition have not been explored adequately. We used two cell lines, DU145 (prostate cancer) and SKOV3 (ovarian cancer), grew them on coverslips and fixed them with 10% NBF at room temperature for 5 min and 12, 15, 18, 36, 108 and 180 h. Aliquots of the same cells were fixed in 10% NBF for 12 h, then transferred to 70% ethanol for 3, 6, 24, 96 and 168 h. Immunostaining with PCNA, Ki67-MIB-1, cytokeratins AE1/AE3 and EGFr was done concomitantly. In both cell lines, immunorecognition decreased between 18 and 36 h of fixation in 10% NBF for PCNA, Ki67-MIB-1 and cytokeratins AE1/AE3. By 108 to 180 h of 10% NBF exposure, there was complete loss of immunorecognition of PCNA and extensive loss of Ki67-MIB-1 and cytokeratins AE1/AE3. The effects on EGFr immunorecognition were less. Transfer to 70% ethanol after fixation for 12 h in 10% NBF preserved immunorecognition of the antibodies.

Topics: Cell Line, Tumor; ErbB Receptors; Ethanol; Female; Fixatives; Formaldehyde; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Ovarian Neoplasms; Proliferating Cell Nuclear Antigen; Prostatic Neoplasms; Solutions; Tissue Fixation

The "corded and hyalinized" pattern, described in endometrioid carcinoma, has not been previously reported in association with serous carcinoma. We describe a unique case of serous neoplasm of low malignant potential with low-grade serous carcinoma combined with a distinct pattern of high-grade carcinoma characterized by cords of epithelioid and spindled cells enmeshed in a hyalinized, collagenous stroma. This pattern was the predominant architecture in the patient's recurrence and caused a diagnostic challenge, as the splenic recurrence was initially diagnosed as a second primary high-grade spindle cell neoplasm. Both ovarian and splenic tumors displayed positive immunohistochemical staining for cytokeratin 7, cytokeratin 8/18, estrogen receptor, and paired box gene 8 (PAX-8) in the conventional serous carcinoma and the corded and hyalinized component, confirming the diagnosis of recurrent carcinoma. The behavior in this unique case of serous carcinoma associated with a distinct corded and hyalinized pattern was more aggressive than low-grade serous carcinoma, but more favorable than malignant mixed mullerian tumor.

Topics: Adult; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Mixed Tumor, Mullerian; Ovarian Neoplasms; Paired Box Transcription Factors; PAX8 Transcription Factor; Receptors, Estrogen; Splenic Neoplasms

We report the first case of primary solid pseudopapillary tumor of the ovary with aggressive behavior and fatal outcome in a 45-year-old woman. The patient presented with weight loss, decrease of appetite, and abdominal bloating for the last several weeks. Computed tomography scan revealed an ovarian mass, omental caking, complex ascites, and 2 hepatic lesions. The pancreas was unremarkable. Grossly, the ovarian mass showed severe capsular adhesion, and the cut surface was cystic and solid. On histologic examination, the tumor was composed of diffuse solid pseudopapillary and pseudocystic patterns. The neoplastic cells were uniform and round with very dispersed chromatin. The cytoplasm was faintly pink. There was mild atypia, but the mitotic rate was as high as 62 per 50 high-power field, and the Ki-67 was elevated at 20%. The tumor exhibited severe necrosis. Numerous foci of lymphovascular invasion were also seen. The tumor cells were positive for cytokeratin (focal) and for β-catenin (cytoplasmic and nuclear patterns). They were negative for chromogranin, synaptophysin, thyroglobulin, calcitonin, hepatocyte-paraffin 1, epithelial membrane antigen, calretinin, and α-inhibin. Electron microscopic study revealed nests of tumor cells with oval nuclei. The cytoplasm contained numerous pleomorphic mitochondria interspersed among short strands of rough endoplasmic reticulum. The tumor involved the fallopian tube, omentum, cul-de-sac, and abdominal wall. The pelvic washing was also positive for tumor cells. Despite chemotherapy, the patient's condition had worsened, and she died of her disease 8 months after the initial diagnosis. We discuss the differential diagnosis of this tumor and the hypothesis of its origin.

Topics: beta Catenin; Biomarkers, Tumor; Carcinoma, Papillary; Cell Nucleus; Diagnosis, Differential; Fatal Outcome; Female; Humans; Keratins; Middle Aged; Mitochondria; Ovarian Neoplasms; Ovary

Malignant transformation is rarely seen in the disease course of mature cystic teratoma (MCT) of the ovary. Adenocarcinoma arising from MCT is especially rare. We herein present the case of a premenopausal woman with a mucinous borderline-like tumor arising from a MCT. Based on the histological transition between the borderline-like tumor and gastrointestinal elements of the MCT, we consider that the tumor derived from teratomatous gastrointestinal epithelium. Immunohistochemistry showed that the proliferating mucinous cells were diffusely positive for cytokeratin 20 and partially positive for cytokeratin 7. MUC5AC was partially positive, whereas MUC2 and MUC6 were positive in a small number of tumor cells. The immunophenotype of cytokeratins and mucins in the present case was compatible with malignant transformation of the teratomatous gastrointestinal epithelium.

Topics: Adenocarcinoma, Mucinous; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucins; Ovarian Neoplasms; Phenotype; Teratoma

Recent studies have suggested that some ovarian and pelvic serous carcinomas could originate from the fimbriated end of the distal fallopian tube. To test this hypothesis, we immortalized a normal human fallopian tube epithelial (FTE) cell line by using retrovirus-mediated overexpression of the early region of the SV40 T/t antigens and the human telomerase reverse transcriptase subunit (hTERT). These immortalized FTEs were then transformed by ectopic expression of oncogenic human HRAS (V12) . Tumorigenicity of the immortalized and/or transformed cells was subsequently tested by anchorage-independence growth assay and inoculation into nude mice via subcutaneous and intraperitoneal injection. As expected, the HRAS (V12) -transformed FTEs produced tumors through both subcutaneous and intraperitoneal injections, whereas no tumor growth was observed in immortalized FTEs. Unexpectedly, histopathological examination of tumors resulting from subcutaneous as well as intraperitoneal injections revealed largely poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma. The tumor implants invaded extensively to the liver, colon, spleen, omentum, adrenal gland and renal capsule. Immunohistochemical staining of tumor cells showed positive staining for the epithelial cell markers cytokeratin AE1/AE3 and Müllerian lineage marker PAX8. Our study demonstrates that FTEs can generate poorly differentiated mucinous adenocarcinoma mixed with undifferentiated carcinoma through genetic modifications. Thus, we provide the first experimental evidence that fimbrial epithelial cells of the fallopian tube could be a potential source of ovarian mucinous adenocarcinoma.

Topics: Adenocarcinoma, Mucinous; Animals; Antigens, Polyomavirus Transforming; Carcinoma; Carcinoma, Ovarian Epithelial; Cell Line, Transformed; Cell Transformation, Neoplastic; Epithelial Cells; Fallopian Tubes; Female; Humans; Immunohistochemistry; Keratins; Mice; Mice, Nude; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Paired Box Transcription Factors; PAX8 Transcription Factor; Proto-Oncogene Proteins p21(ras); Telomerase

The translationally controlled tumor protein (TCTP) plays a role in cell growth, cell cycle and cancer progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased migratory activity of tumor cells and is linked with poor patient outcome. Recent studies indicate that cyclin A,a key regulator of cell cycle, controls actin organization and negatively regulates cell motility via regulation of RhoA expression. We studied the organization of actin and cytokeratin cytoskeleton and the expression of TCTP, p53,cyclin A, RhoA and actin in HIO180 non-transformed ovarian epithelial cells, and OVCAR3 and SKOV3 (expressing low level of inducible p53) ovarian epithelial cancer cells with different metastatic potential. Immunostaining and ultrastructural analyses illustrated a dramatic difference in the organization of the cytokeratin and actin filaments in non-transformed versus cancer cell lines. We also determined that there is an inverse relationship between the level of TCTP/RhoA and actin/p53/cyclin A expression in ovarian cancer cell lines. This previously unidentified negative relationship between TCTP/RhoA and actin/p53/cyclin A may suggest that this interaction is linked with the high aggressiveness of ovarian cancers.

Topics: Actins; Biomarkers, Tumor; Blotting, Western; Cell Line, Tumor; Cyclin A1; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Ovarian Neoplasms; Protein Transport; rhoA GTP-Binding Protein; Tumor Protein, Translationally-Controlled 1; Tumor Suppressor Protein p53

Primary peritoneal serous papillary carcinoma (PPSPC) is a rare primary tumor of the peritoneum that found predominantly in elderly and post-menopausal women. The aim of our study is to review the clinical and pathologic information of 22 patients, and then try to summarize clinical behavior and pathological characteristics of PPSPC, in order to be better recognized of this entity in future. We retrospectively reviewed the data from 22 patients with PPSPC treated at our hospital from 1992 to 2008. All paraffin blocks were recut for periodic acid-Schiff diastase and immunohistochemical staining for CD15, cytokeratin7(CK7), cytokeratin20(CK20), S-100 protein, carcinoembryonic antigen (CEA), CA125, estrogen receptor(ER) and progesterone receptor(PR). The median age of the patients at the time of surgical staging was 56 years (range, 32-77 years). The most common presenting symptoms were abdominal distension (59.1%) and ascites (63.6%). Pretreatment CA125 levels were significant elevated in 90.5% patients. Optimal debulking was performed in 18 patients. All patients were consequently treated with platinum-based chemotherapy. Response to treatment is promising, and the median overall survival of all patients was 21.0 months (95% CI 16.9, 25.1 months). The positive rate of immunohistochemical staining was CD15 95.5%, CK7 90.9%, S-100 protein 68.2%, CA125 59.1%, CK20 31.8%, ER 31.8%, CEA 27.3% and PR 9.1%, respectively. Gynecologist should be aware of PPSPC when abdominal distension, gross ascites and a raised level of CA125 in women without ovarian enlargement. Immunohistochemical staining might be helpful as accessory criteria for the differential diagnosis among the PPSPC, peritoneal malignant mesothelioma (PMM), primary epithelial ovarian carcinoma (PEOC) and peritoneal carcinomatosis from the gastrointestinal tumors (SPCGT). Cytoreductive surgery combined with pre/postoperative platinum-based chemotherapy may be effective for PPSPC patients.

Topics: Adult; Aged; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Carcinoma, Papillary; Cystadenocarcinoma, Serous; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Mesothelioma; Middle Aged; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; S100 Proteins; Survival Rate

Metastasis is a complex, multistep process that begins with the epithelial-mesenchymal transition (EMT). Circulating tumor cells (CTC) are believed to have undergone EMT and thus lack or express low levels of epithelial markers commonly used for enrichment and/or detection of such cells. However, most current CTC detection methods target only EpCAM and/or cytokeratin (CK) to enrich epithelial CTCs, resulting in failure to recognize other, perhaps more important, CTC phenotypes that lack expression of these markers. Here, we describe a population of complex aneuploid CTCs that do not express CK or CD45 antigen in patients with breast, ovarian, or colorectal cancer. These cells were not observed in healthy subjects. We show that the primary epithelial tumors were characterized by similar complex aneuploidy, indicating conversion to an EMT phenotype in the captured cells. Collectively, our study provides a new method for highly efficient capture of previously unrecognized populations of CTCs.. Current assays for CTC capture likely miss populations of cells that have undergone EMT. Capture and study of CTCs that have undergone EMT would allow a better understanding of the mechanisms driving metastasis.

Topics: Biomarkers, Tumor; Breast Neoplasms; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Female; Humans; Keratins; Neoplasm Metastasis; Neoplastic Cells, Circulating; Ovarian Neoplasms

Malignant ascites may be the first presentation of an unsuspected cancer. Pancreas and ovary are among the organs that are usually evaluated as a source of primary. The purpose of this study is to investigate a panel of immunohistochemical stains to help differentiate pancreatic from ovarian carcinoma. We evaluated the immunohistochemical staining of eight commercially available antibodies MUC1, MUC2, MUC5ac, Wilm's tumor susceptibility gene 1 (WT1), cytokeratin 7 (CK7), CK20, CA125, and CA19.9 in 25 effusion specimens with evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9 pancreatic adenocarcinomas, and 2 unknown primaries. Primary ovarian serous carcinomas were positive for WT-1 (100%), CK7 (93%), CK20 (43%), CA125 (100%), CA19.9 (50%), MUC1 (100%), MUC2 (0%), and MUC5ac (0%). Primary pancreatic carcinomas were positive for MUC5ac (100%), MUC1 (100%), CA19.9 (100%), CK7 (78%), CK20 (22%), CA125 (89%), WT-1 (0%), and MUC 2 (0%). The combination of MUC5ac positivity/WT-1 negativity was seen in 100% of pancreatic carcinoma, whereas MUC5ac negativity/WT-1 positivity in 100% of ovarian serous carcinoma. It appears that the combination of MUC5ac and WT-1 stains is useful in distinguishing pancreatic ductal from ovarian serous carcinoma in body fluid cytology.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Pancreatic Ductal; Cystadenocarcinoma, Serous; Cytological Techniques; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Mucin 5AC; Mucin-1; Mucin-2; Neoplasms, Unknown Primary; Ovarian Neoplasms; Pancreatic Neoplasms; WT1 Proteins

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are tumors of unclear histogenesis. The authors analyzed the ultrastructural features of 13 UTROSCT and correlated the findings with their immunohistochemical profile. Features included cells with frequent organoid, nested or cord-like arrangement (8), lumen formation (2; one of which showed surface microvilli), nuclei with irregular indentations (8), intermediate filaments (13), prominent paranuclear aggregates (5), cell junctions (9), desmosome-like junctions (2), tonofilaments (2), basal lamina (1), and cytoplasmic lipid droplets (7; prominent in 3). No dense bodies, subplasmalemmal densities or pinocytotic vesicles were seen. Ultrastructural epithelial differentiation was present in 2 tumors (positive for keratin or epithelial membrane antigen). Prominent lipid droplets correlated with sex cord markers positivity in 2 tumors. Ultrastructural features of smooth muscle differentiation were lacking and abundant paranuclear filaments did not correlate with myoid markers. UTROSCT are polyphenotypic neoplasms ultrastructurally with focal epithelial and variable sex cord-like differentiation. These findings suggest that UTROSCT may result from divergent differentiation in endometrial stromal tumors or represent a distinct group of uterine tumors with sex cord-like differentiation that are closer in histogenesis to ovarian sex cord stromal tumors.

Topics: Adenocarcinoma; Biomarkers, Tumor; Calbindin 2; Cell Nucleus; Cytoplasmic Structures; Desmosomes; Diagnosis, Differential; Female; Humans; Intermediate Filaments; Keratins; Microscopy, Electron, Transmission; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sex Cord-Gonadal Stromal Tumors; Uterine Neoplasms

Topics: Actins; Adult; Carcinoma; Diagnostic Errors; Epithelioid Cells; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors; Tomography, X-Ray Computed; Vimentin

Topics: Aged; Biomarkers; Carcinoid Tumor; Carcinoma, Endometrioid; Diagnosis, Differential; Female; Granular Cell Tumor; Humans; Hysterectomy; Keratin-7; Keratins; Krukenberg Tumor; Middle Aged; Mucin-1; Ovarian Neoplasms; Sertoli Cell Tumor; Sex Cord-Gonadal Stromal Tumors

Cell lines constitute a powerful model to study cancer, and here we describe three new epithelial ovarian cancer (EOC) cell lines derived from poorly differentiated serous solid tumors (TOV-1946, and TOV-2223G), as well as the matched ascites for one case (OV-1946).. In addition to growth parameters, the cell lines were characterized for anchorage independent growth, migration and invasion potential, ability to form spheroids and xenografts in SCID mice.. While all cell lines were capable of anchorage independent growth, only the TOV-1946 and OV-1946 cell lines were able to form spheroid and produce tumors. Profiling of keratins, p53 and Her2 protein expression was assessed by immunohistochemistry and western blot analyses. Somatic TP53 mutations were found in all cell lines, with TOV-1946 and OV-1946 harboring the same mutation, and none harbored the commonly observed somatic mutations in BRAF, KRAS or germline BRCA1/2 mutations found to recur in the French Canadian population. Conventional cytogenetics and spectral karyotype (SKY) analyses revealed complex karyotypes often observed in ovarian disease.. This is the first report of the establishment of matched EOC cell lines derived from both solid tumor and ascites of the same patient.

Topics: Animals; Ascites; Cell Growth Processes; Cell Line, Tumor; Cystadenocarcinoma, Serous; Epithelial Cells; Female; Humans; Karyotyping; Keratins; Mice; Mice, SCID; Mutation; Ovarian Neoplasms; Receptor, ErbB-2; Transplantation, Heterologous; Tumor Suppressor Protein p53

Topics: Carcinoma; Diagnosis, Differential; Female; Humans; Keratins; Middle Aged; Ovarian Neoplasms; Prognosis; Sarcoma

Topics: Carcinoma, Small Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Ovarian Neoplasms

To investigate the common characteristics of a rare entity of ovarian cystic teratoma with intracystic floating balls in conjunction with a case.. Case report.. University hospital.. A 41-year-old woman with abdominal discomfort and a 2-year obscure history of an ovarian cyst.. Right salpingo-oopherectomy by laparotomy.. Ultrasonography and magnetic resonance imaging (MRI).. Ultrasonographic examination revealed a cystic mass (>10 cm) with a unique appearance of multiple floating balls on the lower right quadrant of the abdomen. The MRI showed the same balls with a slightly high fat content. Histopathological diagnosis was mature cystic teratoma and the balls were mostly made of keratin.. The appearance of intracystic floating balls is rarely seen but is pathognomonic for mature cystic teratoma. When this typical appearance is found on ultrasonography the value of other diagnostic tests, such as tumor markers, serological tests for echinococcosis, computerized tomography (CT), and MRI, can be considered as limited.

Topics: Adult; Dermoid Cyst; Female; Humans; Keratins; Magnetic Resonance Imaging; Ovarian Cysts; Ovarian Neoplasms; Ovariectomy; Teratoma; Ultrasonography, Doppler, Color

Ovarian mucinous borderline tumor of müllerian type (MMBT) and mixed epithelial borderline tumor of müllerian type (MEBT) are uncommon subtypes of ovarian surface epithelial tumors. Both are often associated with endometriosis, but their histogenesis is still debated. We have noticed occasional foci of subepithelial cuboidal cells resembling uterine cervical reserve cells (RCs) in MMBTs/MEBTs, which have not been documented in the literature to the best of our knowledge. This study was carried out to identify the presence of RC-like cells (RCLCs) in MMBTs/MEBTs and their immunohistochemical features in comparison to those of cervical RCs. We analyzed 10 consecutive cases of RC-like MMBTs/MEBTs, 6 of which were associated with endometriosis. Immunohistochemistry was performed for p63, cytokeratin 34BE12, cytokeratin 17 (CK17), and low-molecular cytokeratin CAM5.2. In 9 of 10 cases, RCLCs were appreciated in hematoxylin-eosin stain, although their amount in the tumor varied from case to case. Immunohistochemically, RCLCs were positive for p63 in 9 cases. They were positive for both 34BE12 and CK17 and were very weakly positive or negative for CAM5.2 in 8 cases. This immunohistochemical profile is similar to that seen in the cervical RCs. Reserve cell-like cells were also found in the foci of endometriosis coexisting with MMBTs/MEBTs in 1 of 5 cases examined. We draw attention to the existence of the RCLCs in MMBTs/MEBTs and in endometriosis. Their similarity to the cervical RCs may indicate their potential role as precursor cell that may subsequently differentiate into different müllerian cell types, thus merit further study.

Topics: Adult; Aged; Biomarkers; Cell Differentiation; Cervix Uteri; Endometriosis; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratin-17; Keratins; Membrane Proteins; Middle Aged; Mixed Tumor, Mullerian; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms

Mature cystic teratoma of the ovary (MCTO) is the most common type of ovarian teratoma and also the most frequent tumor originating from germ cells. It is usually diagnosed in early adulthood and, by definition, is composed of well-differentiated tissues, which originate from all three germ cell layers. Unusual types of tissues can be found in MCTO, such as kidney, adrenal, and prostatic tissues. Malignant transformation is reported in less than 2% of teratomas. Squamous cell carcinoma is the most common malignancy arising in these otherwise benign tumors. We present the first case of MCTO containing a chordoma. The chordoma differentiation was supported by immunohistochemical staining and interphase fluorescence in situ hybridization (IP-FISH) technique showing 19% of the nuclei of the MCTO displaying polysomy for the chromosome X, while 28% of the chordoma nuclei showed chromosome 7 mosaicism. These results are concordant with previous studies, showing chromosomal anomalies in chromosomes X and 7 in MCTO and chordomas, respectively.

Topics: Adult; Cell Differentiation; Cell Transformation, Neoplastic; Chordoma; Chromosomes, Human, Pair 7; Chromosomes, Human, X; Diagnosis, Differential; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Ki-67 Antigen; Mosaicism; Mucin-1; Ovarian Neoplasms; S100 Proteins; Teratoma; Tumor Suppressor Protein p53; Vimentin

Sertoli-Leydig cell tumours of the ovary account for only 0.2% of malignant ovarian tumours. Two-thirds of all patients become apparent due to the tumour's hormone production.. A 41-year-old patient (gravida 4, para 4) presented with dyspnoea, enlarged abdominal girth and melaena. Diagnostic imaging was suspicious for an ovarian cancer. The standard tumour marker for ovarian cancer (CA 125) was elevated to 984 U/mL.. Surgical exploration of the abdomen revealed a mouldering tumour of both adnexes extending to the level of the navel. Frozen sections showed an undifferentiated carcinoma of unknown origin. Radical surgery was performed. The final histological report described a malignant sex-cord stroma tumour, a Sertoli-Leydig cell tumour, emanating from both ovaries. Analysis of preoperative blood serum showed elevated levels of CYFRA 21-1 (10.4 ng/mL), neuron-specific enolase (36.2 ng/mL), oestradiol (485 pg/mL) and CA-125 (984 U/mL). Adjuvant chemotherapy and regional hyperthermia were performed due to the malignant potential and incomplete resection of the tumour.. Undifferentiated Sertoli-Leydig cell tumours show a poor clinical course. As only two-thirds of patients with this rare disease present with elevated hormone levels, new markers deserve further investigation to offer more specific, individualised tumour monitoring.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Estradiol; Female; Follow-Up Studies; Humans; Keratin-19; Keratins; Ovarian Neoplasms; Phosphopyruvate Hydratase; Sertoli-Leydig Cell Tumor

The omentum is a major site of ovarian cancer metastasis. Our goal was to establish a three-dimensional (3D) model of the key components of the omental microenvironment (mesothelial cells, fibroblasts and extracellular matrices) to study ovarian cancer cell adhesion and invasion. The 3D model comprised of primary human fibroblasts extracted from normal human omentum, mixed with ECM and covered by a layer of primary human mesothelial cells, also from normal human omentum. After addition of ovarian cancer cells, the histological appearance of the 3D culture mimicked microscopic metastases to the omentum from patients with ovarian cancer. When ovarian cancer cells, SKOV3ip.1 and HeyA8, were applied to the 3D omental culture, 60% and 68% of all cells attached, respectively, but only 18% and 25% were able to invade. Ovarian cancer cells preferentially adhered to and invaded collagen I, followed by binding to collagen IV, fibronectin, vitronectin, laminin 10 and 1. Omental mesothelial cells significantly inhibited ovarian cancer cell adhesion and invasion, while omental fibroblasts induced adhesion and invasion. This effect is clearly mediated by direct cell-cell contact, since conditioned medium from mesothelial cells or fibroblasts has a minimal, or no, effect on ovarian cancer cell adhesion and invasion. In summary, we have established a 3D model to study the early steps of ovarian cancer metastasis to the human omentum, and found that omental mesothelial cells inhibit, while omental fibroblasts and the ECM enhance, the attachment and invasion of ovarian cancer cells.

Topics: beta Catenin; CA-125 Antigen; Cell Adhesion; Cell Culture Techniques; Cell Proliferation; Cell Survival; Cells, Cultured; Epithelial Cells; Extracellular Matrix; Female; Fibroblasts; Humans; Immunohistochemistry; Keratins; Microscopy, Phase-Contrast; Models, Biological; Neoplasm Invasiveness; Omentum; Ovarian Neoplasms; Procollagen-Proline Dioxygenase; Tumor Cells, Cultured; Vimentin

Topics: Biomarkers, Tumor; Carcinoma; Cell Differentiation; Dysgerminoma; Female; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Middle Aged; Octamer Transcription Factor-3; Ovarian Neoplasms

Little is known about the behavior of the ovarian surface epithelium (OSE), which plays a central role in ovarian cancer etiology. It has been suggested that incessant ovulation causes OSE changes leading to transformation and that high gonadotropin levels during postmenopause activate OSE receptors, inducing proliferation. We examined the chronology of OSE changes, including tumor appearance, in a mouse model where ovulation never occurs due to deletion of follitropin receptor. Changes in epithelial cells were marked by pan-cytokeratin (CK) staining. Histologic changes and CK staining in the OSE increased from postnatal day 2. CK staining was observed inside the ovary by 24 days and increased thereafter in tumor-bearing animals. Ovaries from a third of aged (1 year) mutant mice showed CK deep inside, indicating cell migration. These tumors resembled serous papillary adenoma of human ovaries. Weak expression of GATA-4 and elevation of PCNA, cyclooxygenase-1, cyclooxygenase-2, and platelet-derived growth factor receptors alpha and beta in mutants indicated differences in cell proliferation, differentiation, and inflammation. Thus, we report that OSE changes occur long before epithelial tumors appear in FORKO mice. Our results suggest that neither incessant ovulation nor follicle-stimulating hormone receptor presence in the OSE is required for inducing ovarian tumors; thus, other mechanisms must contribute to ovarian tumorigenesis.

Topics: Adenoma; Animals; Cell Differentiation; Cell Proliferation; Cyclooxygenase 1; Cyclooxygenase 2; Cystadenoma, Serous; Epithelial Cells; Female; Fluorescent Antibody Technique; GATA4 Transcription Factor; Humans; Immunoenzyme Techniques; Inflammation; Keratins; Mice; Ovarian Neoplasms; Ovary; Proliferating Cell Nuclear Antigen; Receptors, FSH; Receptors, Platelet-Derived Growth Factor

The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Calbindin 2; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Membrane Glycoproteins; Mesothelioma; Microscopy, Electron; Ovarian Neoplasms; Peritoneal Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

In this study, we present the clinicopathologic features and immunophenotypic characteristics of five cases of uterine tumors resembling ovarian sex cord tumors and three cases of endometrial stromal tumors with sex cord-like elements, with emphasis on immunohistochemical markers of sex cord differentiation. The mean patient age was 42 years (range 19-69 years), and vaginal bleeding was the most common clinical presentation. The tumors were usually polypoid masses arising in the uterine fundus, with a mean tumor size of 6.7 cm. Sex cord patterns in uterine tumors resembling ovarian sex cord tumors, including anastomosing cords, trabeculae, small nests, tubules, and in one case, a striking retiform architecture with Leydig-like cells, comprised from 70 to 100% of the tumor volume. All uterine tumors resembling ovarian sex cord tumors were positive for two or more markers of sex cord differentiation; all five cases showed strong immunoreactivity for calretinin, with coexpression of CD99 (four cases), Melan-A (two cases), and inhibin (two cases). Endometrial stromal tumors with sex cord-like elements were less frequently positive for markers of sex cord differentiation, with each case positive for one marker (calretinin, two cases; CD99, one case). In addition, all eight cases were frequently positive for cytokeratin, CD10, vimentin, estrogen receptor, and progesterone receptor; desmin immunoreactivity, when present, was limited to minor foci of smooth muscle. Overall, the morphologic and immunohistochemical findings in uterine tumors resembling ovarian sex cord tumors strongly support that these unusual uterine tumors are polyphenotypic neoplasms with true sex cord differentiation.

Topics: 12E7 Antigen; Adult; Aged; Antigens, CD; Antigens, Neoplasm; Biomarkers; Calbindin 2; Cell Adhesion Molecules; Cell Differentiation; Female; Follow-Up Studies; Humans; Immunohistochemistry; Inhibins; Keratins; MART-1 Antigen; Middle Aged; Neoplasm Proteins; Neprilysin; Ovarian Neoplasms; Receptors, Estrogen; Receptors, Progesterone; S100 Calcium Binding Protein G; Sex Cord-Gonadal Stromal Tumors; Uterine Neoplasms; Vimentin

Topics: Adult; Biomarkers, Tumor; Female; Hormones, Ectopic; Humans; Inhibins; Keratins; Ovarian Neoplasms; Ovary; Paraneoplastic Endocrine Syndromes; Retroperitoneal Neoplasms; Vimentin; Virilism

The purpose of this study was to examine if COX-2, CK7 and CK20 are involved in the malignant transformation of endometriosis.. We compared COX-2, CK7 and CK20 expressions between isolated endometriosis lesions and endometriosis lesions adjacent to ovarian carcinoma and between isolated ovarian carcinoma and ovarian carcinoma with implants of endometriosis. Immunoreactivity was quantified using an immunohistochemical scoring system that corresponds to an image analysis-based system.. There was no difference in COX-2, CK7 and CK20 expressions between the isolated endometriosis lesions and the endometriosis lesions adjacent to ovarian carcinoma. Similarly, CK7 and CK20 were equally expressed between the isolated ovarian carcinoma and the ovarian carcinoma with implants of endometriosis. The COX-2 over-expression rate was greater in ovarian carcinoma that was associated with endometriosis than in isolated ovarian carcinoma (27.8% versus 5.6%, P = 0.083). In endometrioid type ovarian carcinoma, the difference in COX-2 expression was statistically significant (50% versus 0%, P = 0.023).. COX-2 over-expression may be a result of the malignant transformation of endometriosis to endometrioid type ovarian cancer or may represent an interaction between the two cellular components. With respect to cytokeratins, neither CK7 nor CK20 appear to be involved in the malignant transformation of endometriosis.

Topics: Carcinoma, Endometrioid; Cyclooxygenase 2; Endometriosis; Female; Gene Expression Regulation, Neoplastic; Humans; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms

Topics: Adult; Diagnosis, Differential; Female; Heart Neoplasms; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging, Cine; Mixed Tumor, Mullerian; Ovarian Neoplasms

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Breast Neoplasms; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Female; GPI-Linked Proteins; Humans; Immunohistochemistry; Keratin-5; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelin; Mesothelioma; Multivariate Analysis; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity; Stomach Neoplasms; Thrombomodulin; WT1 Proteins

Metastatic tumors to the ovary are infrequently of urinary tract origin. In approximate descending order of frequency, this subset of secondary ovarian neoplasms includes renal cell carcinoma, transitional cell carcinoma of the urinary bladder, and urachal adenocarcinomas. These tumors usually raise a differential in turn of primary ovarian clear cell, transitional cell, or mucinous carcinomas. Only rare metastatic signet-ring adenocarcinomas of the bladder have shown the features of a Krukenberg tumor. We report the case of a 74-year old woman with bilateral Krukenberg tumors metastatic from a primary renal pelvic transitional cell carcinoma with glandular and signet-ring cell differentiation. This unique case reinforces that tumors with signet-ring cell morphology have a propensity to metastasize to the ovary, and indicates that renal pelvic carcinoma rarely may be the source of Krukenberg tumors.

Topics: Aged; Carcinoma, Signet Ring Cell; Carcinoma, Transitional Cell; Cell Differentiation; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Krukenberg Tumor; Ovarian Neoplasms; Prevalence; Urologic Neoplasms

Gastrointestinal adenocarcinoma arising in mature cystic teratomas of the ovary is extremely rare. We report a case of well-differentiated intestinal adenocarcinoma arising in a mature cystic teratoma of the ovary in a 77-year-old woman, presenting as acute abdomen with ovarian torsion. An immunohistochemical study revealed expression of CK20 and CK7, and the tumor was also positive for MUC2. The patient had no evidence of disease after 12 months of follow-up.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Cell Transformation, Neoplastic; Female; Humans; Intestinal Neoplasms; Keratin-20; Keratin-7; Keratins; Mucin-2; Mucins; Neoplasms, Multiple Primary; Ovarian Neoplasms; Teratoma; Tomography, X-Ray Computed; Treatment Outcome

Dysgerminoma is a malignant germ cell tumor of the ovary that shares morphological, immunophenotypic, and genetic features with its testicular counterpart, seminoma. Recent evidence supports the hypothesis that seminoma can differentiate into non-seminomatous germ cell tumor types. The progression of these tumors can be measured by their acquisition of the potential to express cytokeratin intermediate filaments, a characteristic specific to epithelial differentiation. Although testicular seminomas have been widely investigated, little is known about cytokeratin or E-cadherin expression in dysgerminomas. We investigated 26 formalin-fixed, paraffin-embedded ovarian dysgerminomas with immunohistochemical stains for CAM5.2, AE1/AE3, epithelial membrane antigen, cytokeratin 7, cytokeratin 20, high-molecular-weight keratin, and E-cadherin. In addition, we investigated the CD30 and vimentin immunoreactivity of these tumors. Immunoreactivity for CAM5.2 and for AE1/AE3 was present in more than 10% of neoplastic cells in 5 (19.2%) of 26 cases and in 2 (7.7%) of 26 cases, respectively. Cytokeratin 7 showed only focal positivity and never showed positive staining in greater than 10% of dysgerminoma cells. E-cadherin staining was positive in 2 cases showing weak membranous immunostaining in more than 10% of cells. Vimentin immunoreactivity was observed in only 2 dysgerminomas, both of which had less than 10% of the neoplastic cells staining. Cytokeratin 20, epithelial membrane antigen, high-molecular-weight keratin, and CD30 were consistently negative in all cases. Our study demonstrates that cytokeratin expression in dysgerminomas is not unusual and is consistent with the hypothesis that dysgerminomas have the capacity to differentiate along epithelial lines. Furthermore, the immunohistochemical staining patterns for cytokeratins, E-cadherin, and CD30 in dysgerminomas need to be considered when assessing differential diagnoses in difficult cases of primary ovarian tumors.

Topics: Adolescent; Adult; Biomarkers, Tumor; Cell Count; Child; Dysgerminoma; Female; Humans; Immunoenzyme Techniques; Keratins; Ki-1 Antigen; Middle Aged; Ovarian Neoplasms

Coordinate expression profiles for cytokeratins 7 and 20 (CK7 and CK20) are useful for distinguishing certain types of adenocarcinomas but use for distinction of primary and secondary mucinous tumors in the ovary is limited due to the existence of a number of tumor types exhibiting overlapping CK7/CK20 immunoprofiles; the use of staining distribution patterns in the distinction of tumors with shared profiles has not been evaluated in detail. We report analysis of both coordinate expression profiles and staining distribution in 179 rigorously classified mucinous tumors in the ovary, including 53 primary tumors [35 atypical proliferative (borderline) mucinous tumors of gastrointestinal type and 18 invasive mucinous carcinomas] and 126 secondary tumors [28 colorectal adenocarcinomas, 54 appendiceal tumors (23 adenocarcinomas, 31 low-grade adenomatous mucinous tumors associated with pseudomyxoma peritonei), 14 pancreatic adenocarcinomas, 8 endocervical adenocarcinomas, 5 gastric adenocarcinomas, 4 gallbladder/biliary tract adenocarcinomas, and 13 adenocarcinomas of unknown primary sites). A CK7+/CK20+ immunoprofile was the most common profile in primary ovarian tumors (74%), upper gastrointestinal tract tumors (78%), and endocervical tumors (88%) but was occasionally observed in lower intestinal tract tumors (colorectal: 11%; appendiceal: 13% of low-grade tumors, 35% of carcinomas). A CK7-/CK20+ immunoprofile was the most common profile in lower intestinal tract tumors (79%) and was uncommon in upper gastrointestinal tract tumors (9%), rarely seen in primary ovarian tumors (4%), and not seen in endocervical tumors. A CK7+/CK20- profile was observed in some primary ovarian (23%), upper gastrointestinal tract (13%), and endocervical tumors (13%) but not in lower intestinal tract tumors. For CK7+ tumors, staining distribution was very frequently diffuse (>50% of tumors cells positive) in primary ovarian, upper gastrointestinal tract, and endocervical tumors, whereas staining distribution was often focal (<50% of tumors cells positive) when present in colorectal and appendiceal carcinomas but not in low-grade appendiceal tumors. For CK20+ tumors, staining distribution was variable but often focal in primary ovarian tumors and nonlower intestinal tract tumors, whereas the pattern was almost always diffuse in lower intestinal tract tumors. Immunohistochemical staining distribution can supplement CK7/CK20 coordinate expression profiles to distinguish subsets of prim

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Coloring Agents; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Pseudomyxoma Peritonei; Uterine Cervical Neoplasms

It has generally been accepted that pseudomyxoma peritonei/disseminated peritoneal adenomucinosis originates from appendiceal low-grade adenomatous mucinous tumors. A woman who underwent an appendectomy 42 years ago, presented with a unilateral ovarian tumor whose immunohistochemical phenotype and its association with a teratoma, strongly suggest that pseudomyxoma peritonei originated from a ruptured mucinous tumour arising from a mature cystic teratoma.

Topics: Adenoma; Aged; Appendectomy; Douglas' Pouch; Fallopian Tubes; Female; Humans; Hysterectomy; Immunohistochemistry; Keratin-20; Keratins; Omentum; Ovarian Neoplasms; Ovariectomy; Pseudomyxoma Peritonei; Rupture, Spontaneous; Splenectomy; Teratoma

To further develop the hen as a model of ovarian adenocarcinoma, we have studied normal and neoplastic ovaries as well as cultured cells from the ovarian surface epithelium (OSE). We characterized the OSE layer of the hen for specific histologic markers and evaluated these markers on tumor tissue. We also isolated and characterized the epithelial cells that are the likely source of the ovarian tumors of the hen. The surface epithelium of normal ovaries demonstrated positive staining for cytokeratin, proliferating cell nuclear antigen (PCNA), progesterone receptor (PR), and negative staining for vimentin. Ovarian tumors demonstrated positive cytokeratin, PCNA, PR, and weak vimentin staining in the gland-like areas. Epithelial cell cultures were obtained by an explant method utilizing small and large yellow follicles. These cells were positive for cytokeratin and negative for vimentin on Days 1 and 3. By Day 10, cytokeratin protein expression was less for some cells, and vimentin expression was weakly present in some cells. Expression of PCNA was observed at Days 1 and 3, but was rarely seen in cells cultured for 10 days. Expression of PR was observed on Day 10 after 24-hr estrogen treatment. Epithelial cells grew slowly in culture, and were susceptible to trypsin or other dissociation treatments.

Topics: Adenocarcinoma; Animals; Biomarkers; Chickens; Disease Models, Animal; Epithelial Cells; Female; Keratins; Ovarian Neoplasms; Ovary; Proliferating Cell Nuclear Antigen; Receptors, Progesterone; Reference Values; Vimentin

A 49-year-old woman underwent hysterectomy and bilateral adnexectomy after the diagnosis of a right ovarian tumor with paraaortic and pelvic lymph node metastases. The pathological diagnosis was undifferentiated carcinoma of the ovary. After the operation, a bladder tumor was discovered during the evaluation for microscopic hematuria. The bladder tumor was pathologically diagnosed as transitional cell carcinoma, pT1b, G3. Although the pathological findings of the bladder cancer and ovarian cancer were very similar, we could diagnose primary bladder cancer with ovary and lymph node metastases according to the immunohistochemical staining pattern of cytokeratins 7 and 20. Herein, the clinical usefulness of immunohistochemical staining using cytokeratins for making a differential diagnosis of the origin of a tumor in the pelvic cavity is demonstrated.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Ovarian Neoplasms; Urinary Bladder Neoplasms

Three cases of serous borderline tumors of the ovary with areas of serous low-grade carcinoma metastatic to the anterior mediastinum simulating multilocular thymic cysts are presented. The patients are women between the ages of 33 and 50 years. The 3 women had a prior history of primary ovarian neoplasms diagnosed over a period ranging from 3 to 20 years; the 3 patients were in stages IIIA, IIIB, and III. Follow-up radiologic examination revealed the presence of an anterior mediastinal tumor. The 3 patients underwent surgical resection of the mediastinal tumor. Grossly, the mediastinal tumors measured from 7 to 9 cm in greatest diameter and were described as cystic with solid areas. Focal areas of hemorrhage were present, but frank necrosis was not identified. Histologically, all the tumors basically showed similar histopathologic features, namely, those described in multilocular thymic cysts, ie, cystic structures lined by either squamous or low cuboidal epithelium, lymphoid hyperplasia, cholesterol cleft granulomas, and remnants of thymic tissue. In addition, within the cystic structures, there was a neoplastic cellular proliferation with papillary architecture, nuclear atypia, and scattered mitotic figures. Immunohistochemical studies for keratin, MOC31, and CA-125 showed positive staining in tumor cells while placental-like alkaline phosphatase was negative. Two patients remain alive and well after follow-up ranging from 6 to 18 months and 1 patient died of tumor 18 years after initial diagnosis.

Topics: Adult; Biomarkers, Tumor; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Mediastinal Cyst; Mediastinal Neoplasms; Mediastinum; Middle Aged; Ovarian Neoplasms

Metastasis-the spread of tumour cells from a primary lesion to distant organs-is the main cause of cancer-related death, and bone marrow (BM) is a frequent site for the settlement of disseminated tumour cells. Many BM samples harbour isolated tumour cells, whereas tumour cell clusters, as the potential precursors of solid distant metastases, are rarely detected after current enrichment procedures. We have analysed BM samples from 43 patients with carcinomas of the breast, colon and ovaries; 41 of these patients had no clinical signs of overt metastases (stage M0). Tumour cells in BM were enriched with immunomagnetic beads coupled to monoclonal antibodies against both EpCAM and HER2/neu. After enrichment, tumour cells were identified by immunostaining with the anti-cytokeratin antibody A45-B/B3. In total, 886 CK-positive cells were detected in 16 (35%) samples after immunomagnetic enrichment as compared to 34 cells in 9 (21%) samples using Ficoll density centrifugation previously used as the standard enrichment technique. Most remarkably, clusters of 2 to 10 CK-positive cells were found in 75% of CK-positive samples enriched by immunobeads, whereas no CK-positive cell clusters were detected after Ficoll enrichment. The method described offers an excellent tool for the enrichment of micrometastatic tumour cell clusters; these clusters may represent the initial stage of development from a single disseminated tumour cell towards an overt metastasis.

Topics: Bone Marrow Neoplasms; Breast Neoplasms; Cell Separation; Centrifugation, Density Gradient; Colonic Neoplasms; Female; Ficoll; Humans; Immunohistochemistry; Immunomagnetic Separation; Keratins; Male; Neoplasm Metastasis; Neoplasm Staging; Ovarian Neoplasms

We describe unusual cytologic features of the peritoneal fluid in a patient with immature ovarian teratoma. Immature embryonal and neuroectodermal components of such tumors are rarely observed in the ascites; to our knowledge, there have been only three reports of cytologic findings of immature teratoma cells in the ascites. Our patient was a 26-yr-old woman who presented with a huge pelvic mass. A grade 3 immature right ovarian teratoma was diagnosed pathologically. Cytologic examination of the ascitic fluid revealed a variety of neoplastic cells, including immature neuroepithelial cells forming rosette-like structures, keratinized squamous cells, squamoid metaplastic cells, and immature glial-appearing cells. Immunohistochemical analysis revealed that immature gastrointestinal elements and yolk sac elements were positive for alpha-fetoprotein. This is the first description of the cytologic features of non-neuroepithelial elements in the ascitic fluid in a patient with immature ovarian teratoma.

Topics: Adult; alpha-Fetoproteins; Ascitic Fluid; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasm Staging; Ovarian Neoplasms; Teratoma

A solid pattern of tumor cells with a clear cytoplasm is common to both ovarian clear cell carcinoma (OvCCC) and renal clear cell carcinoma (RCCC). This study examined the possible differential expression of CD10 and cytokeratins (CK7, CK20, 34betaE12, and CAM5.2) between these two types. An immunohistochemical technique using peroxidase-labeled amino acid polymers was used to test formalin-fixed and paraffin-embedded tissues. In OvCCC, 6 of 29 cases were positive for CD10, and all cases had expression of CK7, 34betaE12, and CAM5.2. In contrast, all 24 RCCC cases had CD10 and CAM5.2 immunoreactivity, but none had any staining for 34betaE12. CK7 was only expressed in nine cases. No CK20 positivity was observed in any sample from either tumor type. Localization of CD10 expression was different in OvCCC versus RCCC. Although positive staining for 34betaE12 strongly suggests OvCCC, sometimes only a few cells may be stained. Therefore, 34betaE12-negative biopsies also should be evaluated for CD10 and CK7 immunoreactivity to enable histologic and cytologic differential diagnosis.

Topics: Adenocarcinoma, Clear Cell; Biomarkers; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Neprilysin; Ovarian Neoplasms

Distinguishing primary ovarian carcinoma from metastatic carcinoma to the ovary is often difficult by histologic examination alone. Recently an immunohistochemical marker CDX-2 was found to be of considerable diagnostic value in establishing the gastrointestinal origin of metastatic tumors. The aim of this study was to determine whether CDX-2 can distinguish between these malignancies. Paraffin-embedded tissue sections from 57 primary ovarian tumors and 40 metastatic tumors to the ovary were immunostained for CDX-2, and results were compared to the ancillary immunohistochemical results for CK7/CK20, CEA, CA125, and her-2/neu. CDX-2 immunoreactivity was observed in most of metastatic carcinomas with colorectal (91%) and appendiceal (100%) origin, however CDX-2 was negative in all primary ovarian carcinomas, except for the mucinous subtype. Almost all primary ovarian carcinomas including the mucinous subtype showed diffuse and strong immunoexpression for CK7. CEA and CA125 were mainly found in metastatic and primary ovarian carcinoma, respectively. Her-2/neu overexpression was only noted in a small proportion of primary and metastatic ovarian carcinomas. These results suggest that CDX-2 is very useful immunohistochemical marker for distinguishing metastatic colorectal carcinoma to the ovary from primary ovarian carcinoma, including the mucinous subtype. Furthermore, combination with CDX-2 and CK7 strengthen the differential diagnosis between these tumors.

Topics: CA-125 Antigen; Carcinoembryonic Antigen; CDX2 Transcription Factor; Colorectal Neoplasms; Diagnosis, Differential; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasm Metastasis; Ovarian Neoplasms; Receptor, ErbB-2; Tissue Array Analysis; Trans-Activators

We compared the preoperative serum tumor marker values and diameters of ovarian tumors between 14 stage Ia ovarian cancer patients with a good prognosis and 14 stage Ic patients with a poor prognosis. The aim was to examine the usability of tumor markers and diameter of ovarian tumors for prognostic diagnosis of clinically advanced phases. In occult neoplastic cells (ONCs), a tumor marker indicative of recurrence and metastasis, the cytokeratin-positive cells in lymph node biopsies, were also compared. In a preoperative comparison of serum tumor markers, CA125 levels in stage Ia and Ic patients were 47.1+/-15.9 (median, 31.9 U/ml) and 370.6+/-146.2 U/ml (median, 135.6 U/ml), respectively (p=0.0457), and CA19-9 levels were 25.5+/-5.5 (median, 20.4 U/ml) and 564.5+/-192.4 U/ml (median, 248.0 U/ml), respectively (p=0.0131). In a comparison of tumor diameters during surgery, diameters of stage Ia and Ic patients were 117.3+/-11.4 (median, 100.0 mm) and 182.0+/-29.2 mm (median, 145.0 mm), respectively (p=0.0457). ONCs were not detected in any stage Ia patients, but detected in 3 (30%) stage Ic patients. In conclusion, clinical progression was evaluated using CA125 and CA19-9 serum markers and tumor diameters in stage Ia and Ic patients, and demonstrated significant differences between stage. ONCs were only detected in the lymph nodes of stage Ic patients.

Topics: Adult; Aged; Biomarkers, Tumor; Biopsy; CA-125 Antigen; CA-19-9 Antigen; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Ovarian Neoplasms; Prognosis; Time Factors

Surface epithelial-stromal cell tumors are the most common neoplasms of the ovary but occurrence of a serous adenocarcinoma and an adult granulosa cell tumor in the same ovary is an unusual incident. In the present case report we describe this very uncommon occurrence in the ovary of a 50-year-old woman. The patient suffered abdominal distention and was referred to the state hospital where a 5x3 cm multilocular cystic lesion was observed on abdominal CT. Total abdominal hysterectomy with salpingo-oophorectomy and omentectomy was performed. Microscopy revealed an adult granulosa cell tumor and a serous papillary adenocarcinoma in the left ovary. Immunohistochemical staining with inhibin alpha and pancytokeratin confirmed the diagnosis.

Topics: Cystadenocarcinoma, Serous; Female; Granulosa Cell Tumor; Humans; Hysterectomy; Immunohistochemistry; Inhibins; Keratins; Middle Aged; Ovarian Neoplasms; Ovary

Malignant transformation of struma ovarii is exceptional (less than 1%). The histolological diagnosis of malignancy is difficult especially in the well differentiated forms. Immunohistochemistry is highly contributive in the anaplastic forms. The prognosis is relatively favorable except for the metastatic and undifferentiated forms. We report a case of malignant struma ovarii with metastasis observed in a 65-year-old woman who died rapidly from her disease. In light of this observation, we discuss the diagnositic, management and outcome features of these particular tumors.

Topics: Aged; Antineoplastic Agents; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasm Metastasis; Ovarian Neoplasms; Radiotherapy; Struma Ovarii; Thyroglobulin

Histologic differentiation of primary ovarian carcinoma from colonic carcinoma metastatic to the ovary may be difficult. Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunostaining is usually used, but these markers lack specificity for ovarian and intestinal epithelium, and overlapping results have been reported. Cdx2 is a transcription factor whose expression in normal tissues is limited to the intestinal epithelium. It is also expressed in the vast majority of colonic carcinomas and in a sizeable proportion of cases of gastric, pancreatobiliary, and ovarian mucinous carcinomas. We evaluated Cdx2, CK7, and CK20 expression in 50 ovarian carcinomas (15 serous, 20 mucinous, and 15 endometrioid), 15 colonic carcinomas metastatic to the ovaries, and 20 primary colonic carcinomas. The extent (1-25%/1+, 26-75%/2+, >75%/3+) and intensity (weak/1+, strong/2+) of staining were recorded semiquantitatively. All primary and metastatic colonic carcinomas had diffuse (3+) strong Cdx2 reactivity. All serous and endometrioid tumors were Cdx2 negative, whereas mucinous carcinomas had 1+ or 2+ immunoreactivity. All ovarian carcinomas had strong diffuse CK7 staining, whereas all colonic carcinomas were negative for CK7. CK20 stained diffusely and strongly all primary and metastatic colonic carcinomas and was 1+ or 2+ in all mucinous carcinomas, in 67% of serous carcinomas, and in 33% of endometrioid carcinomas. In conclusion, 1) Cdx2 is a highly sensitive (100%) marker for colonic carcinoma metastatic to the ovary; 2) Cdx2 is more specific than CK20 as it is not expressed by serous and endometrioid carcinomas; and 3) a limited panel of Cdx2 and CK7 helps in distinguishing colonic carcinomas metastatic to the ovaries (Cdx2+/CK7-) from primary ovarian serous (Cdx2-/CK7+), endometrioid (Cdx2-/CK7+), and mucinous (Cdx2+/CK7+) carcinomas.

Topics: Biomarkers, Tumor; Carcinoma; CDX2 Transcription Factor; Colonic Neoplasms; Diagnosis, Differential; Female; Homeodomain Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Sensitivity and Specificity; Trans-Activators

The mixed mesodermal tumor is a very uncommon malignancy. The aggressiveness of this lesion is illustrated by extremely poor prospects for afflicted patients: postoperative survival is usually shorter than 24 months. According to the literature, malignant mixed tumor of the ovary is rather rare and its occurrence with other malignancy is exceptional. We report here a case of a 62-years old woman with serous cystadenocarcinoma in the right ovary and a heterologous malignant mixed mesodermal tumor in the left one. Both tumors expressed cytokeratins, while only the mesodermal tumor expressed S-100 and focal NSE.

Topics: Biomarkers, Tumor; Cystadenocarcinoma, Serous; Female; Humans; Keratins; Middle Aged; Mixed Tumor, Mesodermal; Neoplasms, Second Primary; Ovarian Neoplasms; Phosphopyruvate Hydratase; S100 Proteins

Topics: Adenocarcinoma, Mucinous; Carcinoembryonic Antigen; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms

The case of a 62-year-old woman with severe post-menopausal hirsutism is described. Her clinical history revealed regular menstrual periods until menopause at the age of 50, hysterectomy for fibromatosis at 58 years, non-insulin dependent diabetes mellitus, hypertension, obesity, severe hirsutism, which had developed in the previous 3 years, with a deeping of the voice. Examination showed android obesity, hypertension and severe hirsutism involving the face and the trunk. Endocrine evaluation pointed out regular adrenal function, serum total and free-testosterone in the adult male range, with normal androstenedione, DHEAS and 17OHP levels. Estradiol was slightly increased and LH and FSH were inappropriately low for her post-menopausal age. Computed tomography of the abdomen showed regular adrenal glands, and a radio-labeled cholesterol scan was negative. A further pelvic transvaginal ultrasonography revealed a small cystic formation near the right ovary and a slight increase in the size of the left ovary. The patient underwent bilateral ovariectomy. Histological examination showed a lipoid cell tumor within the left ovary. Immunohistochemical studies were positive for inhibin and cytokeratin. After surgery, serum testosterone fell to normal levels, gonadotropins increased to menopausal levels, confirming that the tumor was able to produce both LH, and FSH-inhibiting factors, and hirsutism greatly improved. Periodic hormonal tests remained normal and CT of the abdomen and pelvic ultrasonography did not show alterations at a 3 years follow-up.

Topics: Androgens; Biomarkers, Tumor; Diabetes Mellitus, Type 2; Estradiol; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Hypertension; Inhibins; Keratins; Luteinizing Hormone; Middle Aged; Neoplasms, Gonadal Tissue; Obesity; Ovarian Neoplasms; Ovariectomy; Virilism

A 9-year, 7-month-old female German shepherd weighing 26.6 kg was admitted to the hospital for pica and diarrhea. A large mass was found in the right ovary and removed, and cross section of the mass revealed a multilobular tumor consisting of several cystic cavities which contained tufts of dark hair in thick creamy-white sebaceous fluid. Histologically, the tumor consisted of adipose tissue, central nervous tissue, crystalline lens, cartilage and bone. In the central nervous tissue, lens and lesions like nonsuppurative inflammation comprizing of accumulation of glial cells and lymphocytic perivascular cuffing were observed. The tumor was diagnosed as a mature cystic teratoma.

Topics: Adipose Tissue; Animals; Cartilage; Dog Diseases; Dogs; Female; Immunohistochemistry; Keratins; Lens, Crystalline; Ovarian Neoplasms; S100 Proteins; Teratoma; Vimentin

Topics: Adult; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Ovarian Neoplasms; Prostate; Prostate-Specific Antigen; Teratoma

Yolk sac tumors (YSTs) have a variety of morphologic patterns, some of which can resemble either endometrioid adenocarcinoma (EAC) or clear cell carcinoma (CCC). Immunohistochemical staining for alpha-fetoprotein (AFP) is usually only focal and thus is not always helpful in the diagnosis of YST, and pancytokeratin (CK) is expressed by all three tumors. We studied a battery of immunohistochemical markers with specific attention to the utility of cytokeratin 7 (CK7) in differentiating YST from EAC and CCC. A total of 46 ovarian tumors were retrieved for this study: 16 YST, 19 EAC, and 11 CCC. The three groups were analyzed for the expression of CK7, AFP, Leu-M1 (CD15), EMA, and WT1 by immunohistochemistry. In addition, CK and c-kit (CD117) were studied in the YSTs. All of the YSTs tested (100%) were positive for CK. CK7 was considered negative in all 16 YST cases (100%), although a few tumor cells (1%-2%) stained in 4 cases. In contrast, 17 of 19 EACs and all 11 CCCs had diffuse 3+ to 4+ positivity for CK7; the two other EACs showed 2+ positivity for CK7 (40% and 30% of the tumors). AFP was positive in 12 of 15 YSTs (80%), but was generally focal with 1+ staining in 10 cases (67%); only 2 cases were 3+. All of the EACs and CCCs were negative for AFP. Leu-M1 was 1+ in 9 of 15 YSTs (60%), while the remaining 6 were considered negative. Leu-M1 was positive in 10 of 15 EACs tested (67%), but the staining was variable with 1 case 3+, 3 cases 2+, and 6 cases 1+. In the CCCs, 10 cases (91%) were 3+ to 4+, and 1 case was 1+. EMA was essentially negative in 15 of 15 YSTs (100%), with 3 completely negative and 12 showing very focal (<5%) staining. Eight of 12 EACs showed 4+ staining, 3 showed 3+ staining, and 1 showed 2+ staining. All of the 11 CCCs (100%) showed 4+ staining. WT1 was negative in all cases of YST and CCC; 16 of 18 EAC tested (89%) were negative for WT1, but 2 (11%) were 4+ positive. C-kit was negative in all YSTs. In conclusion, it is important for pathologists to be aware that YSTs may mimic EACs and CCCs and that this distinction is important for the clinical management of patients with these tumors. AFP staining is focal in most YST, so an absence of staining does not exclude this diagnosis. CK7 and EMA are essentially negative in YST but are diffusely positive in CCC and EAC, making them useful markers for differentiating YSTs from both CCCs and EACs. Leu-M1 may also be helpful for distinguishing YSTs from CCCs.

Topics: Adenocarcinoma, Clear Cell; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Endometrioid; Diagnosis, Differential; Endodermal Sinus Tumor; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lewis X Antigen; Mucin-1; Ovarian Neoplasms; Proto-Oncogene Proteins c-kit; WT1 Proteins

The aim of this study was to determine the effects of exogenous expression of the catalytic subunit of telomerase (hTERT) on the lifespan, growth characteristics, and tumorigenicity of normal human ovarian surface epithelial (OSE) cells.. Low-passage primary cultures of normal human OSE cells were transfected with hTERT and the resulting cell lines were characterized.. The ectopic expression of hTERT stabilized the telomeres of the OSE cultures above 8 kb. The hTERT-transfected OSE cell lines grew beyond the normal lifespan seen in OSE cells and propagated in culture for more than 40 passages before senescing. Moreover, the hTERT-transfected cells demonstrated extensive proliferative capacity as evidenced by their ability to continuously grow even when seeded at low dilutions. The morphologic features and normal differentiation patterns seen in normal OSE cells were likewise retained by the hTERT-transfected cells. In addition, the cultures remained responsive to physiologic concentrations of epidermal growth factor and transforming growth factor-beta. Changes associated with neoplastic transformation like anchorage-independent growth, tumorigencity and karyotypic instability were not observed.. We were able to show that the ectopic expression of hTERT in normal human OSE: 1) resulted in cultures with greater growth potential and longer lifespan and 2) did not induce a transformed phenotype previously seen in viral oncogene-transfected OSE cells. The established cell lines would not only provide sufficient material for comprehensive studies to investigate the normal physiology of OSE cells, but could also help in the understanding of the early steps of ovarian carcinogenesis.

Topics: Animals; Cell Differentiation; Cell Division; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; DNA-Binding Proteins; Epidermal Growth Factor; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Mice; Mice, SCID; Ovarian Neoplasms; Ovary; Telomerase; Transfection; Transforming Growth Factor beta; Tumor Cells, Cultured

In many investigation it was demonstrated that intratumor microvessel density (IMD) is the best factor for no tumor survival for patients with ovarian cancer. Occult axillary node micrometastases as the prognostic factor for the patients with breast cancer was proved, but currently no literature of the pelvic lymph node micrometastases in ovarian cancer is provided. This study try to detect the microvessel density of tumor tissues and micrometastases of regional lymph nodes in ovarian cancer and to investigate the relationship between these two factors and their prognostic significance.. The sections of ovarian cancer from 39 patients were stained immunohistochemically for cytokeratin(CK) and factor VIII-related antigen (F8-RA). Microvessels on the section were counted by computerized morphometry (40 fields). Sections of 212 regional lymph nodes from 39 patients were stained also with HE and CK.. (1)We found 7 lymph node metastases with HE staining in 39 patients and 12 micrometastases with CK staining.(2) Average value of intratumor microvessel density (IMD) in the HE positive group was 48.86+/-16.60 and was obviously higher than that in the HE negative group (29.16+/-10.02,P< 0.01). The average IMD was 41.67+/-21.69 in the CK positive group and was also obviously higher than that in the CK negative group (28.70+/-10.77,P< 0.05). We found 8(50%) micrometastases in 16 patients with higher IMD (> or = 30/40 x fields) and only 4(17.4%) micrometastases in 23 patients with lower IMD (< 30/40 x fields), the difference was significant (P< 0.05). (3)IMD (P=0.03) and regional lymph node micrometastases(P=0.04) were the most significant factors to the survival time through Cox proportional hezard model analysis,the IMD (P=0.0008) and clinical stage (P=0.03) were also the most important factors to predict recurrence.. The study suggests the CK immunohistochemical staining could detect the micrometastases in the HE negative lymph node in patients with epithelial ovarian cancer. The IMD is closely related to the micrometastases and these two factors have prognostic significance in ovarian cancer. The IMD and micrometastases could act as independent prognosis factors of patients with ovarian cancer.

Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neovascularization, Pathologic; Ovarian Neoplasms

We report a urachal adenocarcinoma metastatic to both ovaries in a 50-year-old Japanese woman. Pelvic examination and imaging studies revealed a large cystic tumor occupying the pelvis and another cystic tumor between the umbilicus and the urinary bladder. A laparotomy was performed. Histopathological examination revealed a urachal tumor that was a well-differentiated invasive mucinous adenocarcinoma; the overlying urothelium was intact. The right and left ovarian tumors were well-differentiated mucinous adenocarcinomas. The urachal and ovarian tumors were immunoreactive for cytokeratin 20 and carcinoembryonic antigen, but negative for cytokeratin 7. The patient is alive with lymph node and bone metastases 6 months postoperatively. This is the eighth reported case of an adenocarcinoma of the bladder with ovarian metastasis.

Topics: Adenocarcinoma, Mucinous; Adult; Bone Neoplasms; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lymphatic Metastasis; Ovarian Neoplasms; Urachus; Urinary Bladder Neoplasms

The diagnosis of primary clear cell carcinoma of the ovary or kidney is usually straightforward. However, problems in ascertaining the site of the primary tumor may arise when there is widespread metastatic disease or when clear cell carcinoma is present in both the ovary and kidney. In this study, the value of a panel of antibodies in distinguishing between an ovarian and renal clear cell carcinoma was evaluated. The panel comprised cytokeratin (CK)7 and 20, vimentin, estrogen receptor (ER), CD10, and renal cell carcinoma (RCC) marker. Ovarian clear cell carcinomas (n=14) were positive with CK7 (14/14), vimentin (6/14), ER (2/14), and RCC marker (2/14). All were negative with CD10 and CK20. Renal clear cell carcinomas (n=14) were positive with CD10 (14/14), RCC marker (14/14), vimentin (7/14), CK7 (2/14), and CK20 (1/14). All were negative with ER. This panel allows clear cell carcinomas of the ovary and kidney to be distinguished with a high degree of certainty and is a useful adjunct to histologic examination. Primary ovarian clear cell carcinomas are characterized by CK7 positivity, whereas primary renal neoplasms are characterized by positivity for CD10 and RCC marker and negative staining with CK7.

Topics: Antibodies; Biomarkers, Tumor; Carcinoma, Renal Cell; Coloring Agents; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Neprilysin; Ovarian Neoplasms; Receptors, Estrogen; Vimentin

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are unusual neoplasms with histologic features that resemble those within ovarian Sertoli and granulosa cell tumors. We report the case of a 24-year-old woman with a UTROSCT presenting as a cervical mass, which on initial evaluation was thought to represent cervical adenocarcinoma. The patient's cervical biopsy specimen contained epithelioid cells arranged in tubules and anastomosing cords, without significant cellular atypia or mitotic activity. Because this morphology elicited a broad differential diagnosis, immunohistochemical studies were performed. The tumor was found to be diffusely positive for cytokeratin cocktail, calretinin, and desmin, focally positive for CK7 and SMA, and negative for EMA, CEA, inhibin, CD10, CK20, chromogranin, and synaptophysin. Ultrastructural examination revealed occasional gland-like lumens with cells joined by desmosomes and a continuous basal lamina. UTROSCTs have features that may cause them to be confused with more common tumors, especially in limited biopsy samples, and should be included in the differential diagnosis when a gland-forming neoplasm with an unusual appearance is identified in a cervical or endometrial biopsy specimen.

Topics: Actins; Adenocarcinoma; Adult; Biopsy; Calbindin 2; Cell Nucleus; Cytoplasm; Desmin; Diagnosis, Differential; Female; Humans; Hysterectomy; Immunohistochemistry; Keratin-7; Keratins; Microscopy, Electron; Muscle, Smooth; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sex Cord-Gonadal Stromal Tumors; Uterine Cervical Neoplasms; Uterine Neoplasms

Pure sebaceous neoplasms arising in dermoid cysts of the ovary are exceedingly rare. A 63-year-old female with abdominal swelling and pain underwent a right salpingo-oophorectomy that showed a unilocular cyst weighing 830 g and measuring 15x12x10 cm, filled with sebaceous material containing a few hair shafts. The cyst wall exhibited plaques protruding into the cavity of the cyst. Microscopy revealed a dermoid cyst with nests and lobules of atypical and infiltrating sebaceous cells surrounded by basaloid cells. The tumor cells stained diffusely for high-molecular-weight cytokeratins and focally for cytokeratin 7, cytokeratin 19, epithelial membrane antigen and carcinoembryonic antigen in the immunohistochemistry study. Low-molecular-weight cytokeratins, cytokeratin 20, vimentin, S100, p63, estrogen receptor, progesterone receptor, p53 and c-erbB-2 were negative in tumoral cells. The proliferative labeling index (Ki67 and proliferating cell nuclear antigen) was low. Basal cell carcinoma with sebaceous differentiation and sebaceoma must be considered in the differential diagnosis. However, the presence of obvious malignant sebaceous differentiation in nearly every tumor nest and lack of peripheral palisading and peri-tumoral myxoid stroma excluded these diagnoses. Some histogenetic concepts relevant to this case are discussed along with a brief review of this neoplasm. To our knowledge, this is the sixth case report of a sebaceous carcinoma arising in a mature cystic teratoma of the ovary.

Topics: Adenocarcinoma, Sebaceous; Carcinoembryonic Antigen; Dermoid Cyst; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Ovarian Neoplasms; Proliferating Cell Nuclear Antigen

Mature cystic teratomas of the ovary frequently contain intestinal type epithelium, but they are rarely associated with complete intestinal wall. The association of mature cystic teratoma with mucinous cystadenoma is not unusual. However, the pathogenetic relationship between these two lesions remains unanswered. We report a mature cystic teratoma of the ovary in a 16-yr old female that contained a complete colonic wall in continuity with an endocervical-type mucinous cystadenoma. Both the mucinous cystadenoma and the colonic wall showed the typical histopathological and immunohistochemical patterns of classical mucinous cystadenoma (positive for CK7, negative for CK20) and normal colonic wall (positive for CK20, negative for CK7), respectively. The microscopic and immunohistochemical patterns of the epithelium from the transitional zone between colonic wall-like structure and mucinous cystadenoma demonstrated features of both types of epithelium, positive for both CK7 and CK20, and focally positive for a neuroendocrine marker, chromogranin, which is normally present in colonic mucosa. These results suggest that the mucinous cystadenoma originated from the colonic epithelium of the mature cystic teratoma.

Topics: Adolescent; Colon; Cystadenoma, Mucinous; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasms, Multiple Primary; Ovarian Neoplasms; Staining and Labeling; Teratoma

We report a case of an adult-type granulosa cell tumor of the ovary which was diagnosed in a 20-yr-old woman. After a 21-yr disease-free interval, she developed a pelvic recurrence, followed by a splenic metastasis and, more recently, omental masses. This report is concerned with the fine-needle aspiration (FNA) diagnosis of the granulosa cell tumor in the latter site and corroboration of the interpretation by immunocytochemistry. Only one previous case is similar to the present one documenting the role of immunocytochemistry in the evaluation of suspected metastatic granulosa cell tumor. The cytopathologic features of metastatic granular cell tumor have been described in a limited number of previous reports.

Topics: Adult; Biopsy, Needle; Diagnosis, Differential; Female; Granulosa Cell Tumor; Humans; Immunohistochemistry; Inhibins; Keratins; Neoplasm Recurrence, Local; Omentum; Ovarian Neoplasms; Peritoneal Neoplasms; Splenic Neoplasms; Vimentin

The distinction of metastatic mucinous carcinomas in the ovary from primary ovarian mucinous tumors (atypical proliferative/borderline and carcinoma) can be difficult because of similarities in morphology. We evaluated the immunohistochemical expression of cytokeratins 7 and 20 (CK 7, CK 20), Dpc4 (nuclear transcription factor inactivated in 55% of pancreatic carcinomas), and MUC5AC (a gastric mucin gene) in 57 primary ovarian mucinous tumors (41 atypical proliferative tumors and 16 carcinomas) and 46 metastatic mucinous carcinomas in the ovary. Primary ovarian mucinous tumors were virtually always diffusely positive for CK 7 (98%), Dpc4 (100%), and MUC5AC (98%) and often focally to diffusely positive for CK 20 (68%). Colorectal mucinous carcinomas were diffusely positive for CK 20 (100%) and Dpc4 (89%) and were distinguished from primary ovarian mucinous tumors by their frequent lack of expression of CK 7 and MUC5AC (67% were negative for each marker). Appendiceal carcinomas were diffusely positive for CK 20 (100%) and often negative for CK 7 (71%) but were often positive for MUC5AC (86%) and Dpc4 (100%). When primary ovarian and metastatic colorectal or appendiceal carcinomas shared expression of both CK 7 and CK 20, they could usually be distinguished by the pattern of positivity (diffuse CK 7 and patchy CK 20 in ovarian tumors and patchy CK 7 and diffuse CK 20 in colorectal and appendiceal tumors). Pancreatic carcinomas shared the same pattern of diffuse positivity for CK 7 (100%) and MUC5AC (92%) and focal to diffuse positivity for CK 20 (71%) as primary ovarian mucinous tumors but were negative for Dpc4 in 46%. Loss of Dpc4 expression is useful for distinguishing metastatic pancreatic carcinomas in the ovary from both primary ovarian mucinous tumors and metastatic mucinous carcinomas derived from other sites.

Topics: Adenocarcinoma, Mucinous; Appendiceal Neoplasms; Biomarkers, Tumor; Colorectal Neoplasms; Diagnosis, Differential; DNA-Binding Proteins; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin 5AC; Mucins; Ovarian Neoplasms; Pancreatic Neoplasms; Smad4 Protein; Trans-Activators

Ten mucinous cystic ovarian tumors that contained sarcoma-like mural nodules are described. The nodules were studied by conventional and immunohistochemical methods. The sarcoma-like mural nodules occurred predominantly in middle-aged women, were multiple and sharply demarcated from the adjacent mucinous tumor, had small size, and exhibited a heterogeneous cell population. Distinction of these lesions from true sarcomatous nodules and foci of anaplastic carcinoma is important because of the worse prognosis of the two latter tumors compared with the favorable behavior of the sarcoma-like mural nodules. Six of the eight patients with follow-up information were alive and clinically free of recurrence at a mean follow-up interval of 12 years. Two patients died of other causes (thyroid and breast carcinomas). The nature of the nodules is not clear. Sarcoma-like mural nodules probably represent a reactive and self-limited phenomenon within a neoplasia. Their coexpression of vimentin and cytokeratins is consistent with an origin from submesothelial mesenchymal cells, which undergo partial transformation into epithelial cells.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Combined Modality Therapy; Cystadenocarcinoma, Mucinous; Diagnosis, Differential; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Sarcoma; Vimentin

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas. We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive. The proportion of CK7+/CK20- was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7-/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20-, whereas 19% (8 of 43) were CK7-/CK20+. All colorectal cancers metastatic to the ovary were CK7-/CK20+, except 1 case that was CK7-/CK20-. In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma.

Topics: Adenocarcinoma; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms; Tissue Embedding

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In the current studies, exposing A2780 ovarian cancer cells to the histone deacetylase inhibitor trichostatin A (TSA) produced a marked change in cellular morphology, proliferation, and differentiation. Within 24 h of TSA treatment, there was a morphological transformation of the cells, with increased cytoplasm, a more epithelial-like columnar appearance, and the emergence of distinct cellular boundaries. Commensurate with the morphological transformation, TSA also inhibited cell proliferation; cells treated with TSA for 72 h increased to 110% of the initial cell numbers versus control cell numbers of 622%, with a corresponding reduction in mitotic activity and a flow cytometry S-phase fraction of 3.9% in TSA-treated cells versus 28.8% for control. TSA also induced epithelial-like differentiation with increased cytokeratin expression from 2% of controls to 22-25% of TSA-treated cells and the reappearance of intercellular plasma membrane junctions and primitive microvilli. Immunocytochemical analyses indicate the molecular mechanism underlying the actions of TSA on A2780 cell cycle progression and differentiation involves reexpression of the CDK inhibitor p21. Elevated levels of p21, in TSA-treated cells, were associated with a reduction in the phosphorylation of the cell cycle regulator retinoblastoma protein (Rb). TSA also caused a decrease in the helix-loop-helix inhibitor of differentiation/DNA binding protein Id1, with no change in Id2 levels. In conclusion, the observed TSA-induced changes in p21, Rb, and Id1 are consistent with cell cycle senescence and differentiation of A2780 ovarian cancer cells.

Topics: Cell Cycle; Cell Differentiation; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; DNA-Binding Proteins; Enzyme Inhibitors; Epithelial Cells; Female; Flow Cytometry; Helix-Loop-Helix Motifs; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Immunoenzyme Techniques; Inhibitor of Differentiation Protein 1; Inhibitor of Differentiation Protein 2; Keratins; Ki-67 Antigen; Microfilament Proteins; Microscopy, Electron; Microvilli; Muscle Proteins; Ovarian Neoplasms; Phosphorylation; Repressor Proteins; Retinoblastoma Protein; Transcription Factors; Tumor Suppressor Protein p53

The outcome of patients with advanced ovarian cancer is poor despite aggressive therapy including surgery and multiagent chemotherapy. Valid prognostic factors are necessary to estimate the course of the disease and to define biologically similar subgroups for analysis of therapeutic efficacy.. This study is the first published prospective study concerning the prognostic significance of DNA-ploidy and S-phase fraction in ovarian cancer following enrichment of tumor cells by cytokeratin labeling. Epithelial cells were labeled by FITC-conjugated cytokeratin antibody (CK 5, 6, 8, and 17) prior to flow cytometric cell cycle analysis in 129 fresh specimens of primary ovarian cancer.. Recurrence-free survival of patients with DNA-diploid primary ovarian cancer was significantly better compared to that of patients with DNA-aneuploid tumors in univariate analysis (47% vs 18%, P = 0.01). The tumor-dependent overall survival of patients with DNA-diploid tumors was 57% compared to 30% with DNA-aneuploid tumors (P = 0.04). In FIGO stage III ovarian cancer DNA-ploidy, optimized by cytokeratin gating for tumor cells, achieved independent prognostic significance. No significance was found for S-phase fraction. However, despite convincing methodological advantages in the detection of DNA-aneuploid subpopulations the clinical significance of cytokeratin gating of epithelial cells was only marginal.. DNA-ploidy has been shown to be as powerful or even more so in comparison to postoperative residual tumor in multivariate analysis for predicting clinical outcome in advanced ovarian cancer. Thus, determination of DNA-ploidy should be introduced to currently recruiting phase III studies for therapy of ovarian cancer for better definition of prognostic subgroups.

Topics: Adult; Aged; Aged, 80 and over; Disease-Free Survival; DNA, Neoplasm; Female; Flow Cytometry; Humans; Keratins; Middle Aged; Multivariate Analysis; Neoplasm Staging; Ovarian Neoplasms; Ploidies; Prospective Studies; S Phase

To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum.. Paraffin-embedded formalin-fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber-EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcinoma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas.. Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.

Topics: Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; CA-125 Antigen; Calbindin 2; Carcinoembryonic Antigen; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Diagnosis, Differential; Epithelium; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratin-5; Keratins; Lewis X Antigen; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms; Predictive Value of Tests; S100 Calcium Binding Protein G; Thrombomodulin

A case of uterine tumors resembling ovarian sex-cord tumors (UTROSCT) producing parathyroid hormone-related protein (PTH-rP) of the uterine cervix is reported. A 66-year-old woman underwent total hysterectomy with bilateral salpingo -oophorectomy due to the possibility of a malignant uterine tumor. A fairly well-circumscribed tumor, measuring 8 x 5 x 7 cm, was present in the myometrium of the cervix and extended into the endocervical mucosa. Histologically, the tumor showed predominantly sex-cord-like differentiation and the features of conventional endometrial low-grade stromal sarcoma were observed in part. Immunohistochemically, the tumor cells were negative for CD10. From these findings, we diagnosed the present case as Clement and Scully's group II UTROSCT arising from the uterine cervix. To our knowledge, this is the first report of the cervical occurrence of UTROSCT. Furthermore, in this tumor, production of PTH-rP was demonstrated by normalization of serum PTH-rP after the tumorectomy and immunoreactivity for PTH-rP in the tumor cells.

Topics: 12E7 Antigen; Aged; Antigens, CD; Cell Adhesion Molecules; Cervix Uteri; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Parathyroid Hormone-Related Protein; Protein Biosynthesis; Sex Cord-Gonadal Stromal Tumors; Uterine Neoplasms; Vimentin

To further delineate specific staining patterns and refine the differential usefulness of cytokeratin (CK) 7/20 staining, we studied multiple ovarian tumors and primary nongynecologic neoplasms likely to metastasize to the ovary. Immunohistochemical analysis with semiquantitative grading to give quartile scores (0-4) was performed on 127 cases. Subsequent analysis indicated that a more informative diagnostic segregation could be achieved with a biphasic grading system (>50% staining, positive; 50% or less, negative). Lower intestinal tumors were CK7- and usually CK20+, while upper gastrointestinal tumors, including those of pancreatobiliary origin, were mostly CK7+ and CK20-. Serous papillary ovarian tumors were all CK7+ and CK20-. Mucinous ovarian carcinomas were all CK7+ and slightly more often CK20-, whereas the small number of ovarian borderline mucinous tumors studied were the most problematic, with no clear pattern. Multiple different tumor types from all nonovarian gynecologic sites were fairly consistently CK7+ and almost always CK20-. Differential CK staining of mucinous tumors of the female genital tract using CK7 and CK20 is useful for predicting the site of origin, provided samples are adequate in size. The most specific usefulness is the identification of lower gastrointestinal vs "other" neoplasms.

Topics: Adenocarcinoma, Mucinous; Female; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms

To evaluate the frequency of tumor cell contamination in autologous peripheral-blood progenitor cells from patients with ovarian cancer, and to determine the impact of infusing such cells on relapses after high-dose chemotherapy.. Seventy-three samples of peripheral-blood progenitor cells from 24 ovarian cancer patients were studied for contaminated tumor cells by cytokeratin 7 and cytokeratin 20 reverse transcriptase polymerase chain reaction.. Tumor cell contamination in peripheral-blood progenitor cells was detected in 11 of 24 patients (46%) and, among these, in four of 11 patients who received transplantations of peripheral-blood progenitor cells. There was no trend towards longer relapse-free survival in patients infused with cytokeratin-negative peripheral-blood progenitor cells as compared with positive ones. Interestingly, two of four patients who received transplantations of peripheral-blood progenitor cells containing tumor cells were free from progression at 20 and 41 months after transplantation.. Tumor cell contamination of peripheral-blood progenitor cells was frequently noted by transcriptase polymerase chain reaction in patients with ovarian cancer. The biological and clinical significance of this finding remains to be elucidated.

Topics: Adult; Antineoplastic Agents; Disease-Free Survival; DNA Primers; Female; Hematopoietic Stem Cell Transplantation; Humans; Keratins; Middle Aged; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Ovarian Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stem Cells

Gynecologic metastasis of breast carcinoma is not an infrequent event, but metastases within another tumor is very rare. We report a case of unilateral ovarian tumor arising in a 63-year-old woman receiving tamoxifen therapy with a past history of breast carcinoma. The microscopic appearance was principally that of a granulosa cell tumor, but the presence of atypical cells closely admixed within the classical areas was reminiscent of metastasis from breast carcinoma. The diagnosis of this first reported case of breast carcinoma metastasis within granulosa cell tumor was supported by immunohistologic analysis. The diagnosis of tumor-to-tumor metastasis was also confirmed by molecular study using microdissections of samples from the initial breast tumor and from the subsequent ovarian tumor. When compared with normal tissue, carcinomatous cells in the breast tissue exhibited genomic abnormality at the same locus as the metastatic cells in the ovary. In contrast, granulosa cell tumor areas did not show any loss of heterozygosity or instability for the microsatellites analyzed.

Topics: Apolipoproteins; Apolipoproteins D; Breast Neoplasms; Carcinoma, Lobular; Carrier Proteins; Cell Nucleus; Cytoplasm; Female; Glycoproteins; Granulosa Cell Tumor; Humans; Keratin-7; Keratins; Loss of Heterozygosity; Membrane Transport Proteins; Microsatellite Repeats; Middle Aged; Mucin-1; Neoplasm Metastasis; Neoplasms, Multiple Primary; Ovarian Neoplasms

Several studies have reported on the use of antibodies to monoclonal carcinoembryonic antigen (CEA) and vimentin (VIM) to distinguish between adenocarcinomas of endometrial (EM) and endocervical (EC) origin, with variably enthusiastic results. It is still unclear whether site of origin or pathway of differentiation (endometrioid [em] versus mucinous [m]) is more important in predicting immunohistochemical differences. In the present study, paraffin blocks from adenocarcinomas of known origin were retrieved and immunostained with monoclonal antibodies to VIM and CEA, as well as cytokeratins (CK) 4, 18, and 20, estrogen receptor (ER), and progesterone receptor (PR). Positivity was scored on a scale from 0 to 12, with emphasis on the pattern of differentiation (tumors with mixed patterns received separate scores for the em and m foci). Mean CEA scores for emEM (n = 27), mEM (17), mEC (10), and emEC (6) were 0.4, 0.9, 5.1, and 1.2, respectively. VIM scores were 6.9, 1.3, 0, 4.4; ER, 5.7, 4.2, 0, 1.6; PR, 7.6, 2.8, 0.1, 6.0; CK4, 9.2, 4.4, 8.5, 10.6; CK18, 6.4, 3.4, 5.5, 8.4; CK20, 0.7, 0, 0.5, 0.4. Both site and differentiation influenced these results, with the latter more important for VIM and PR, the former for ER, both for CEA (only mEC was frequently strongly positive), and neither for the CKs studied. No one stain or combination reliably distinguished endometrial from endocervical origin. The only immunostaining pattern that might identify a site of origin with more accuracy than hematoxylin & eosin evaluation alone is the combination of high VIM and ER scores in an endometrioid carcinoma, suggesting with about 95% accuracy in this series an endometrial origin of the tumor.

Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Ovarian Neoplasms; Receptors, Estrogen; Receptors, Progesterone; Uterine Cervical Neoplasms; Vimentin

Based on conventional tumor staging, primary ovarian cancer is viewed as an intraperitoneal disease that rarely spreads to extraperitoneal organs. However, autopsy studies reveal a much higher rate of occult metastasis, indicating that extraperitoneal spread occurs with much greater frequency than previously appreciated. Consequently, we investigated the incidence of early hematogenous dissemination and its association with distant disease-free and overall survival.. Bone marrow aspirates from 108 patients newly diagnosed with International Federation of Gynecology and Obstetrics stage I to III ovarian cancer were prospectively analyzed with the novel anti-cytokeratin (CK) antibody A45-B/B3. We investigated the frequency of CK-positive tumor cells in bone marrow and their effect on prognosis in relation to established risk factors for tumor progression.. Tumor cells in bone marrow were detected in 32 (30%) of 108 patients. A CK-positive finding was unrelated to established risk parameters, except for poor nuclear grading of the primary tumor. At a median follow-up of 45 months (range, 12 to 77 months), the presence of occult metastatic cells in bone marrow was associated with the occurrence of clinically overt, extraperitoneal (predominantly extraskeletal) distant metastasis (relative risk [RR], 16.5; 95% confidence interval [CI], 6.2 to 56.9; P < .0001) and death from cancer-related causes (RR, 2.3; 95% CI, 1.2 to 4.3; P = .01). Multivariate analysis identified a positive bone marrow finding as an independent prognostic factor of reduced distant disease-free survival for all patients (RR, 13.8; 95% CI, 5.4 to 52.9; P < .0001) and for the 64 stage R0-1 patients (RR, 7.3; 95% CI, 1.5 to 56.8; P = .0021).. Our data signal that hematogenous dissemination of tumor cells occurs early and throughout all stages of ovarian cancer. The clinical significance of our findings is supported by the unfavorable prognosis in association with the presence of occult metastatic cells, especially in those patients who received an effective locoregional therapy.

Topics: Adult; Aged; Antibodies, Neoplasm; Bone Marrow; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Staging; Neoplastic Cells, Circulating; Ovarian Neoplasms; Prognosis; Proportional Hazards Models; Prospective Studies; Survival Analysis

To determine whether Brenner tumors and transitional cell carcinomas (TCCs) of the ovary are urothelial in type, the immunoprofiles of 14 Brenner tumors, including three malignant examples, and eight ovarian TCCs were compared with those of Walthard nests, urothelium, 12 urinary bladder TCCs and 17 ovarian adenocarcinomas (serous, endometrioid, mucinous, and undifferentiated type). The immunohistochemical stains used included those for cytokeratins CKs 5/6, CK7, CK8, CK13, and CK20, vimentin, CA125, and the specific urothelial differentiation marker uroplakin III. CK7 and CK8 were broadly expressed in most tumors of ovary and bladder examined, while vimentin was focally present in some ovarian TCCs and adenocarcinomas. As in normal and neoplastic bladder urothelium, urothelial markers, including uroplakin III, CK13, and CK20, were detected in the epithelial nests of Brenner tumors. Brenner tumor cells also expressed uroplakins Ia and II. CA125 was observed focally in some Brenner tumors. In contrast, TCCs of the ovary and Walthard nests lacked uroplakins and were essentially negative for CK20 and CK13 but quite strongly expressed CA125. This immunophenotype closely resembled that found in ovarian adenocarcinomas. Thus, it appears that the only true urothelial-type ovarian neoplasm is the Brenner tumor, whereas ovarian TCC most likely represents a poorly differentiated adenocarcinoma with a morphologic transitional cell pattern. These results may explain the controversies as expressed in the recent literature concerning TCC of the ovary and establish its place among the ovarian adenocarcinomas of müllerian type.

Topics: Adenocarcinoma; Brenner Tumor; Carcinoma, Transitional Cell; Cell Transformation, Neoplastic; Female; Humans; Keratins; Membrane Glycoproteins; Ovarian Cysts; Ovarian Neoplasms; Urinary Bladder Neoplasms; Uroplakin III; Urothelium

Renal clear cell carcinoma rarely metastasizes to the ovary potentially mimicking a primary ovarian clear cell carcinoma. The immunocytochemical profiles of the two tumors were compared. Control groups of ovarian endometrioid and serous adenocarcinomas were also examined using the same antibody panel. Paraffin sections were studied with the immunocytochemical technique using eight antibodies. Renal clear cell carcinomas were positive for vimentin (8/12 cases), CK5/6 (0/12), 34 beta E12 (1/12), Ber-Ep4 (5/12), CA125 (0/12), ER (1/12), and PGR (1/12). Ovarian clear cell carcinomas showed positivity with vimentin (1/10 cases), CK5/6 (2/10), 34 beta E12 (10/10), Ber-Ep4 (10/10), CA125 (8/10), ER (7/10), and PGR (6/10). Endometrioid adenocarcinomas were positive for vimentin (9/10 cases), CK5/6 (8/10), 34 beta E12 (10/10), Ber-Ep4 (9/10), CA125 (9/10), ER (9/10), and PGR (10/10). Eight serous adenocarcinomas were positive in all cases for all the antibodies except CK5/6 (7/8 cases) and 34 beta E12 (7/8 cases). All the tumors reacted for epithelial membrane antigen. This immunohistochemical panel allows clear cell carcinomas of kidney and ovary to be distinguished. The latter has a greater phenotypic similarity with serous and endometrioid adenocarcinomas than with renal clear cell carcinoma demonstrating yet again that these ovarian tumors share a common histogenetic origin.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Aged, 80 and over; Antigens, Surface; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Renal Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Middle Aged; Mucin-1; Ovarian Neoplasms; Receptors, Estrogen; Receptors, Progesterone; Vimentin

Topics: Adult; Female; Humans; Keratins; Magnetic Resonance Imaging; Ovarian Neoplasms; Ovary; Teratoma; Ultrasonography

Malignant mixed mesodermal tumor is a rare tumor of the ovary and its histogenesis is controversial. We report the case of an ovarian tumor that seemed to be a pure carcinoma and recurred as a carcinosarcoma, and suggest a possible histogenesis for this kind of tumor. The patient was a 62-year-old Japanese woman. The primary tumor was confined to the right ovary and was a histologically poorly differentiated endometrioid adenocarcinoma with focal squamous differentiation. The tumor recurred as peritoneal dissemination 9 months later showing a histological appearance of carcinosarcoma of heterologous type. The recurrent tumor also contained intermingled foci of similar histology as the primary tumor. The carcinomatous component of the recurrent tumor showed more obvious differentiation to adenocarcinoma with increased expression of epithelial markers compared to the primary tumor. Epithelial membrane antigen was positive also in a few cells of the sarcomatous component, which implies that this tumor had features of metaplastic carcinoma. The DNA ploidy pattern of the primary ovarian tumor was diploid, while an additional aneuploid subpopulation appeared in the recurrent tumor. These findings suggest the possible histogenesis of carcinosarcoma of the ovary as progression and clonal evolution of endometrioid adenocarcinoma.

Topics: Carcinoma, Endometrioid; Carcinosarcoma; DNA, Neoplasm; Female; Humans; Image Cytometry; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; Neoplasm Recurrence, Local; Ovarian Neoplasms; Ploidies; Vimentin

The distribution of cytokeratins (CKs) and vimentin in the normal genital tract of calves and cows at different stages of the oestrous cycle and in epithelial tumours of the tract was studied immunohistochemically. Few differences in CK and vimentin immunolabelling were detected in relation to age or stage of the oestrous cycle. Coexpression of CKs in simple epithelia and in basal cells of stratified epithelia was detected in the oviduct and endocervix; this coexpression was different from that previously described in women. The demonstration of CKs but not vimentin in the neoplastic cells of a serous superficial ovarian papilloma suggested an origin from the ovarian surface epithelium, while the coexpression of CKs and vimentin in serous papillary and mucinous cystadenomas pointed to a possible origin from the rete ovarii. Studies on three uterine adenocarcinomas and the ovarian metastases from two of these showed an endometrial-CK phenotype. The intermediate filament profile of normal endometrium, conserved in uterine adenocarcinomas and their ovarian metastases, may be useful in discriminating between ovarian metastases from endometrial carcinomas and those originating from primary carcinomas in other organs.

Topics: Adenocarcinoma; Age Factors; Animals; Antibodies, Monoclonal; Cattle; Cattle Diseases; Cystadenoma; Estrus; Female; Genitalia, Female; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms; Ovary; Oviducts; Papilloma; Uterine Neoplasms; Uterus; Vimentin

We investigated whether a panel of antibodies including WT1 could separate pancreaticobiliary and ovarian carcinomas by staining 64 pancreaticobiliary adenocarcinomas, 41 ovarian serous carcinomas, and 12 primary ovarian mucinous neoplasms with WT1, cytokeratin (CK) 17, CK20, carcinoembryonic antigen (CEA), and CA-125. Moderate or strong intensity reactivity in more than 25% of cells was a positive result. Of the ovarian serous carcinomas, 38 (93%) were WT1 reactive and 22 (54%) WT1 positive, 9 (22%) had CK20 reactivity, and 3 (7%) were CK20 positive in fewer than 50% of cells. All were CK17 or CEA nonreactive. Of the ovarian mucinous neoplasms, all were WT1 and CK17 nonreactive and 11 (92%) were CEA reactive, 8 (67%) CEA positive, 10 (83%) CK20 reactive, and 6 (50%) CK20 positive. Of the pancreaticobiliary adenocarcinomas, 19 (30%) were CK20 positive, 27 (42%) CK17 positive, and 52 (81%) CEA positive. All were WT1 nonreactive. A panel including WT1, CK17, CK20, and CEA is useful to distinguish pancreaticobiliary and ovarian serous carcinomas. Extensive CK17 reactivity is supportive of a pancreaticobiliary adenocarcinoma when the differential diagnosis includes ovarian mucinous neoplasm. None of the antibodies positively identified ovarian mucinous neoplasms.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antibodies; Biliary Tract Neoplasms; CA-125 Antigen; Carcinoembryonic Antigen; Cystadenocarcinoma; Diagnosis, Differential; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Ovarian Neoplasms; Pancreatic Neoplasms; Transcription Factors; WT1 Proteins

The Sertoli-stromal cell tumor (SSCT) of the ovary shows a histologic resemblance to developing or adult testes and is often associated with virilization caused by tumor-produced androgenic hormone. In spite of the unique manifestation of SSCT, detailed characteristics of this tumor are still obscure. The mechanism by which SSCT occurs has not yet been determined. Six SSCTs were studied immunohistochemically, ultrastructurally, and by polymerase chain reaction (PCR) for the presence of sex-determining region Y (SRY) gene and the X chromosome activation state. Immunohistochemically, Sertoli-like cells of SSCT were positive not only for alpha-inhibin but also low-molecular-weight cytokeratin. In control testes, the expression of alpha-inhibin and cytokeratin was limited to a Sertoli cell component and rete testis, respectively. Ultrastructurally, tumor cells composing hollow tubules had an elongated nucleus with deep indentation and annulate lamellae, which are characteristic structures of mature Sertoli cells. In addition, they had studded microvilli on the apical surface and frequent desmosomes, which are structures noted in the cells of rete testis. Histologically, tumor cells of hollow tubules sometimes pouted into the lumen, as did the cells of tubulae rete, entrance into rete testis from seminiferous tubules. All of these findings indicate that some tumor cells of a SSCT show simultaneous differentiation into both Sertoli cells and cells of rete testis. SRY gene was not detected in any cases, and the X chromosome activation pattern was the same as that of the female control.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; DNA Primers; DNA-Binding Proteins; DNA, Neoplasm; Female; Humans; Immunoenzyme Techniques; Inhibins; Keratins; Male; Microsatellite Repeats; Nuclear Proteins; Ovarian Neoplasms; Polymerase Chain Reaction; Sex Cord-Gonadal Stromal Tumors; Sex Determination Analysis; Sex-Determining Region Y Protein; Testicular Neoplasms; Transcription Factors; X Chromosome

Primary ovarian carcinomas with unusual histologic patterns can be difficult to differentiate from metastases. In this study, we reviewed 15 cases of mixed-epithelial carcinoma (12 serous, 1 serous and endometrioid, 1 endometrioid, 1 undifferentiated) with a predominant microcystic pattern and signet-ring cells. The patients' ages ranged from 31 to 78 (mean 58) years. The microcystic component in 11 patients had features of high-grade carcinoma and in 4 patients had features of low-grade carcinoma associated with areas of borderline tumor. The tumors in all 15 patients showed a predominant microcystic growth pattern composed of small cysts that were variable in size and shape. Signet-ring cells were also present in all cases (diffusely in nine cases, focally in six cases) within the neoplastic epithelial proliferation. Mucin was present in the lumina of some of the microcysts and in the cytoplasm of most of the signet-ring cells. A microcystic pattern and mucin-containing signet-ring cells can be seen as small foci or as a predominant component in primary epithelial nonmucinous ovarian carcinomas. It is important for pathologists to recognize these unusual findings in ovarian neoplasms, because they may produce a confusing apperance, even potentially suggesting a metastasis.

Topics: Adult; Aged; Carcinoma; Carcinoma, Endometrioid; Carcinoma, Signet Ring Cell; Cell Nucleus; Cystadenocarcinoma; Cystadenocarcinoma, Papillary; Cytoplasm; Female; Humans; Keratins; Middle Aged; Mucins; Ovarian Cysts; Ovarian Neoplasms

Cell lines are valuable in vitro models for clinical and basic research. Most ovarian cancer cell lines described are serous cystadenocarcinomas or poorly differentiated adenocarcinomas. The establishment of ovarian cancer cell lines with rare histologic differentiation is especially of interest. We describe the establishment of a carcinosarcoma cell line of the ovary after in vivo selection.. The cell line OV-MZ-22 was established from a solid tumor mass in the upper abdomen. At the time of establishment, the patient underwent secondary debulking and was pretreated with six cycles of cis-platinum/epirubicin/cyclophosphamide. Features of the cell line studied included morphology, ultrastructure, heterotransplantation, chromosome analysis, and analysis of intermediate filament proteins and actins by immunocytochemistry.. The first histologic report of the patient described a papillary cystadenocarcinoma, which changed to a carcinosarcoma with predominantly sarcomatous differentiation at secondary debulking. This cell line is aneuploid and shows no expression of the tumor-associated antigens CA-125 and CEA, but an overexpression of MDR-1, lung resistance protein, p53, and topoisomerase I and II, but not of multidrug-resistance-associated protein. The cell line did not give rise to transplant tumors in nude mice. The histologic and immunocytochemical comparison of the primary and the relapsed tumor proved evidence of an in vivo change of differentiation from predominantly papillary cystadenocarcinoma to carcinosarcoma. Morphological characteristics and intermediate filament pattern underlined the sarcomatous differentiation and origin of this cell line. The differentiation phenotype of OV-MZ-22 cells is that of smooth-muscle cells.. The change of histologic differentiation was apparently due to a selection process caused by platinum-containing chemotherapy. The origin of the cell line and its rarity make this new line an appropriate tool for further investigation.

Topics: Actins; Animals; Carcinosarcoma; Cell Differentiation; Cystadenocarcinoma, Papillary; DNA, Neoplasm; Female; Humans; Intermediate Filament Proteins; Karyotyping; Keratins; Mice; Mice, Nude; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Transplantation; Ovarian Neoplasms; Tumor Cells, Cultured

To study the immunohistochemical feature and the differential diagnosis of adenomatoid tumors in uterus and ovaries.. Clinical pathological analysis and immunohistochemical studies were performed on 24 cases of adenomatoid tumors in the uterus and ovaries.. Of the 24 cases, 21 cases were in the uterus, 2 cases in the ovaries and 1 cases in both the uterus and the ovary. Grossly, the mean diameter of the 22 uterus tumors was 2.2 cm, ranging from 0.2 - 5.5 cm. 14 (63.6%) were located in the subserosa or near by the subserosa of the uterine cornua. The other 8 tumors located in the myometrium. The cut surface presented a nodular pattern with grayish white or yellowish in color, partially cystic. 3 ovarian tumors became all cystic, without a clear-cut margin from the surroundings. Microscopically, the tumor consisted of various gland-like structure or luminal spaces lined with flat, cuboidal or low columnar cells, similar to blood vessels in structure. Among the tumor cells, there were scattered vesicular cells with large or small vacuoles, but no nuclear atypia and mitotic figures detected. Immunohistochemical staining showed the tumor cells positive for vimentin, AE(1)/AE(3) and calretinin, but negative for F VIII-Rag. S-100 and EMA were positive in 20 (83.3%) and 4 (16.7%) cases respectively.. Adenomatoid tumor of the female genital tract is mesothelial in origin and uterus was considered as the most common site of occurance. Immunohistochemical phenotypes can be used as an important evidence for differential diagnosis. The biological behavior of adenomatoid tumor is benign and with a good prognosis.

Topics: Adenomatoid Tumor; Adult; Calbindin 2; Diagnosis, Differential; Female; Humans; Keratins; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; S100 Calcium Binding Protein G; S100 Proteins; Uterine Neoplasms; Vimentin

To study the distinctive clinicopathologic and immunohistochemical difference between ovarian metastatic carcinomas and primary ovarian carcinomas.. The clinical and pathological features of 27 cases of ovarian metastatic carcinomas (gastric carcinomas 12 cases, colon carcinomas 11 cases, others 4 cases) obtained from our department were reviewed. Immunostainings for CK (AE1/AE3), CK7, CK20, CEA, vimentin, nm23 were performed with SP staining methods.. On gross examination, metastasis from gastric adenocarcinoma were usually bilateral, while solid (11/12) and metastases from colonic adenocarcinoma were more often unilateral and cystic (7/11). Microscopically, metastases from gastric adenocarcinoma revealed signet ring cells or poorly differentiated adenocarcinomas (12/12), whereas metastases from colonic adenocarcinomas showed similar morphology of endometrioid adenocarcinoma (8/11). The majority of ovarian metastases of gastric carcinoma (7/12) and colon carcinoma (8/11) were CK20 positive. In particular, CK20 was invariably expressed in colon cancer metastases. Most of the ovarian metastatic carcinomas from the gastrointestinal tract failed to react with immunostaining of CK7. A combined use of CEA, vimentin and nm23 had made a correct classification for 11/12 cases of the gastric carcinoma, 10/11 cases of the colonic cancer.. CK7 and CK20 have been proved to be useful antibodies in distinguishing between metastatic carcinomas and primary carcinomas of the ovary. Combined use of a panel of antibodies can give more significant results.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Genes, Tumor Suppressor; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Ovarian Neoplasms; Stomach Neoplasms; Vimentin

A rare case of serous papillary cystadenocarcinoma of the ovary showing chondrosarcomatous differentiation in a metastatic deposit late in the clinical course is reported. A 49-year-old female underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for bilateral ovarian tumors. Histological diagnosis was serous papillary cystadenocarcinoma of both ovaries with lymph node metastasis. After six courses of chemotherapy, she was confirmed to be in complete remission following a second laparotomy. Following additional chemotherapy, a third laparotomy disclosed swollen left inguinal lymph nodes. In one of these nodes, approximately 5.0 cm in greatest diameter, the predominant histological features were: chondrosarcoma of the bone and soft tissue, with small foci of serous papillary adenocarcinoma and squamous epithelium. A histological transition between mesenchymal and epithelial areas was identified. Immunohistochemical positivity for broad-spectrum cytokeratin (AE1/AE3), vimentin, epithelial membrane antigen, and S-100 protein was observed in both chondrosarcomatous and epithelial areas. The current evidence may suggest that the chondrosarcomatous differentiation was derived from the metastatic epithelial component.

Topics: Cell Differentiation; Chondrosarcoma; Cystadenocarcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Mucin-1; Ovarian Neoplasms; S100 Proteins; Vimentin

A case is reported of yolk sac tumor occurring in the left ovary and complicated by pregnancy. The 22-year-old patient presented at 28 weeks gestation with virilization and elevated serum levels of testosterone and alpha-fetoprotein. The tumor showed the typical features of yolk sac tumor with a mixture of islands of Leydig cells. The accumulations of Leydig cells were well demarcated from the cellular components of the yolk sac tumor and were distributed throughout the tumor, although with predominant localization at the periphery. By immunohistochemistry the Leydig cells were intensely positive for vimentin and negative for cytokeratins, allowing clear distinction from the cell components of the yolk sac tumor, which were positive for cytokeratins and negative for vimentin. Testosterone was also identified in the cytoplasm of the Leydig cells. After tumor resection the testosterone and alpha-fetoprotein levels declined simultaneously; this, together with the immunohistochemical demonstration of testosterone, indicates that the Leydig cells were responsible for the endocrine manifestations. Furthermore, antibodies against inhibin alpha-subunit and calretinin could be used to detect the Leydig cells. The present case, a combination of yolk sac tumor and Leydig cells acting as a functioning stroma and causing virilization during pregnancy, is very rare.

Topics: Adult; alpha-Fetoproteins; Endodermal Sinus Tumor; Female; Humans; Immunohistochemistry; Keratins; Leydig Cells; Male; Ovarian Neoplasms; Pregnancy; Pregnancy Complications; Stromal Cells; Testosterone; Virilism

The aim of this case report was to evaluate the impact of immunohistochemical markers in diagnosing the primary site of adenocarcinoma in the abdominopelvic region.. Surgicopathologic data were obtained from laparotomy and necropsy. Paraffin-embedded tissue from the ovary and jejunum was stained with hematoxylin and eosin, as well as with immunohistochemical stains for cytokeratin 20 and cytokeratin 7.. A 53-year-old African American woman underwent an emergency laparotomy due to small bowel obstruction. During the operation, in addition to a complex adnexal mass as the cause of obstruction, a small solid jejunal tumor was also identified. Pathologic evaluation of the two sites demonstrated an infiltrating moderately to poorly differentiated adenocarcinoma with mucinous features. The malignant cells from both intestinal and ovarian sites showed immunoreactivity for cytokeratin 20 and revealed negative staining for cytokeratin 7. These results confirmed the diagnosis of intestinal primary with ovarian metastasis, which was initially misdiagnosed as an ovarian primary.. Given the potential difficulty in determining the primary site of these tumors, immunohistochemistry proved to be a useful tool in reaching the correct diagnosis.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Intestinal Obstruction; Jejunal Neoplasms; Keratin-20; Keratin-7; Keratins; Middle Aged; Ovarian Neoplasms

The clinicopathological, immunohistochemical and aetiological aspects, with respect to asbestos, of seven primary gonadal mesotheliomas (three intratesticular, four ovarian) are described and compared. These tumours are extremely rare, poorly described and the knowledge of their natural history is very limited.. The cases were collated from the UK Health and Safety Executive Mesothelioma Register over a 24-year period (1968-91). Primary mesotheliomas of the tunica vaginalis and ovary comprised 0. 09% (10 cases) and 0.03% (three cases) of mesothelioma deaths, respectively. No primary intratesticular (non-tunica vaginalis) malignant mesotheliomas have been described. In this study, we present seven (three intratesticular, four ovarian) primary malignant gonadal mesotheliomas. In both genders the tumours show a similar age distribution (with median onset in the sixth decade), a similar association with asbestos (in approximately 50% cases), a diverse histological spectrum (with predominantly tubulopapillary epithelial subtype tumours) and an immunophenotype that is comparable with malignant pleural and peritoneal mesothelioma. The clinical course appears variable (mean, 26 months; range, 9-50 months). All tumours in the study presented as localized masses and their prognosis appeared more favourable than that of diffuse pleural and peritoneal cases.. An awareness of the existence of these rare forms of malignant mesothelioma is important to prevent misdiagnosis. Immunohistochemistry has an important role in confirmation of the diagnosis. The accurate diagnosis of primary gonadal mesothelioma has potentially important medicolegal compensation considerations as a significant proportion of these cases are associated with asbestos.

Topics: Adult; Aged; Asbestos; Calbindin 2; Carcinogens; Fatal Outcome; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Ovarian Neoplasms; S100 Calcium Binding Protein G; Testicular Neoplasms; Thrombomodulin

Topics: Animals; Antigens, Neoplasm; Cell Adhesion; Cell Division; Female; Genes, erbB-2; Humans; Karyotyping; Keratins; Mice; Mice, Nude; Microsatellite Repeats; Mutation; Neoplasm Transplantation; Ovarian Neoplasms; Prognosis; Tumor Cells, Cultured

Germline mutations in the BRCA1 tumor suppressor gene are associated with increased risk for the development of ovarian cancer. All such cancers thus far reported have been of the epithelial histologic type. We identified an ovarian dysgerminoma in a 16-year-old woman (proband) with a family history of ovarian cancer during a review of histopathologic characteristics of ovarian cancers from women enrolled in the Gilda Radner Familial Ovarian Cancer Registry. Mutation analysis of DNA from this patient's peripheral blood leukocytes revealed a germline BRCA1 mutation (3312insG). The mutation was also present in the mother with breast cancer, a maternal aunt and a distant cousin with ovarian cancer, and a maternal grandfather and an uncle with skin cancer. The development of the proband's dysgerminoma may be unrelated to her germline BRCA1 mutation. Alternatively, such dysgerminomas may be caused by BRCA1 mutations, but occur so infrequently compared with epithelial cancers that they are seldom identified. Analysis of a larger series of ovarian germ cell tumors may resolve this question.

Topics: Adolescent; alpha-Fetoproteins; Breast Neoplasms; Chorionic Gonadotropin, beta Subunit, Human; DNA Mutational Analysis; Dysgerminoma; Female; Genes, BRCA1; Germ-Line Mutation; Humans; Keratins; L-Lactate Dehydrogenase; Ovarian Neoplasms; Pedigree; Polymorphism, Single-Stranded Conformational

A 47-year-old woman developed metastatic melanoma to the right ovary 14 years after the enucleation of the right eye for a choroidal spindle cell melanoma. An immunohistochemical study was performed on paraffin sections of both primary and metastatic melanoma specimens to identify markers of both aggressive phenotype and metastatic potential with particular attention to the anomalous expression of cytokeratin intermediate filament proteins. Neoplastic cells of both primary and metastatic tumors immunostained positively for S-100, HMB45, MART-1, and vimentin antibodies, but they were negative for cytokeratins 1-19, 8, 18, and 8,18; <10% of neoplastic cells in both the primary and the metastatic melanomas immunostained for Ki-67 proliferating antigen using MIB-1 antibody. We speculate that the indolent behavior of this ovarian metastasis is reflected by the absence of coexpression of cytokeratins 8 and 18 with vimentin. This case supports the practical value of using this panel of antibodies to evaluate the aggressive potential of uveal melanomas.

Topics: Antigens, Neoplasm; Carcinoma; Choroid Neoplasms; Female; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratins; Ki-67 Antigen; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Ovarian Neoplasms; S100 Proteins; Time Factors; Vimentin

Atypical epithelial cells in the bone marrow of patients with ovarian cancer were evaluated using immunohistochemical techniques. We investigated cytospin preparations of bone marrow taken from 9 women with benign ovarian tumors and 59 women with malignant ovarian tumors. Two monoclonal antibodies (NCL-C11 and NCL-CA 125) were used. With both antibodies we were able to detect keratin and CA 125 antigen expression in the bone marrow of 9 (18.4%) of the patients with ovarian cancer. With regard to the wide histological differentiation of ovarian carcinomas, the presence of atypical epithelial cells in the bone marrow was required as a prognostic factor for survival and relapses. This should be investigated in a larger study group.

Topics: Adult; Aged; Bone Marrow; Bone Marrow Neoplasms; CA-125 Antigen; Female; Humans; Keratins; Middle Aged; Ovarian Neoplasms; Prognosis; Survival Rate

A 70-year-old woman presented with metastatic psammoma body-rich papillary carcinoma in a supraclavicular lymph node. No primary site was evident. The tumour showed strong staining for CA125 and weak staining for thyroglobulin. Prompted by this case we aimed to assess the reliability of immunostaining for CA125 and thyroglobulin in making the distinction between thyroid and ovarian papillary carcinoma.. Nine papillary carcinomas of the thyroid and 17 serous papillary carcinomas of the ovary were stained for CA125 and thyroglobulin, as well as CAM 5.2, LP 34, carcinoembryonic antigen (CEA), S100 and diastase/periodic acid-Schiff. Nine of nine thyroid carcinomas stained for thyroglobulin; in addition CA125 was positive in four of nine. Normal surrounding thyroid also showed some reaction. Seventeen of 17 ovarian serous carcinomas were positive for CA125; in addition one case showed moderately strong staining for thyroglobulin. Mucin stains were positive in 14/17 ovarian serous carcinomas, but negative in all thyroid carcinomas. The other antibodies assessed showed no useful differences in staining frequency.. Many cases of papillary carcinoma of the thyroid show CA125 staining, and this feature therefore has little positive predictive value for an ovarian origin. Occasional cases of ovarian papillary carcinoma may show staining for thyroglobulin, and this result should therefore be interpreted cautiously.

Topics: Aged; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Mucins; Ovarian Neoplasms; S100 Proteins; Thyroglobulin; Thyroid Neoplasms

We report a case of a 43-year-old woman with the simultaneous presence of a primary uterine endometrial cancer and metastasis of breast cancer to the ovary after 5 years of tamoxifen therapy. Tamoxifen therapy lengthens recurrence-free survival of the patient. However, the risk of endometrial cancer and the possibility of recurrence of breast cancer also must be considered.

Topics: Adult; Antigens, Neoplasm; Antineoplastic Agents, Hormonal; Breast Neoplasms; Endometrial Neoplasms; Fallopian Tubes; Female; Humans; Hysterectomy; Keratins; Neoplasm Recurrence, Local; Ovarian Neoplasms; Ovariectomy; Receptors, Estrogen; Tamoxifen

A Sertoli cell carcinoma of the ovary with lung metastases mimicking neuroendocrine carcinoma is presented. Lung metastases frequently occur. Primary and secondary tumors may exhibit similar growth patterns and differentiating primary from secondary tumors may be troublesome. This process may be more difficult when metastases occur from a tumor in which metastases are uncommon and morphologically resemble only a small portion of the primary tumor. We report the case of a 52-year-old woman who underwent resection of a 4,550-g Sertoli cell tumor of the ovary. Histologically, in addition to the characteristic tubular pattern of growth, 5% of the tumor consisted of poorly differentiated areas with tumor cells in sheets, a high mitotic rate, and areas of necrosis. Eleven months after this surgery she presented at a different institution with multiple pulmonary nodules. Microscopic examination of a subsequently resected lung nodule showed histologic findings similar to those of the poorly differentiated areas of the ovarian tumor and initial immunohistochemical studies showed positive staining for cytokeratin, neuron-specific enolase, and focal positivity for synaptophysin. Without knowledge of the ovarian tumor the lung lesion was interpreted as large-cell neuroendocrine carcinoma. On review of the clinical history and comparison with the previous surgical material, however, both tumors showed similar light microscopy and immunohistochemical reactivity, and a final diagnosis of metastatic Sertoli cell tumor was made. Immunohistochemical staining for inhibin revealed weak positivity in the poorly differentiated areas of the ovarian tumor but not in the lung metastasis. This is one of the rare reports of ovarian Sertoli cell tumor metastasizing to the lungs and it emphasizes the importance of complete clinical histories, ancillary studies, appropriate sampling, and review of archival material in such unusual cases.

Topics: Carcinoma, Neuroendocrine; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Inhibins; Keratins; Lung Neoplasms; Middle Aged; Ovarian Neoplasms; Phosphopyruvate Hydratase; Sertoli Cell Tumor; Synaptophysin

Collagenous spherulosis (CS) is a rare lesion which is an incidental finding in breast and salivary glands. It is characterized by fibrillar spherules exhibiting an intrinsic radiating or concentric pattern which are surrounded by myoepithelial cells. This entity can be misdiagnosed as adenoid cystic carcinoma and in-situ ductal carcinoma.. We report here the first case of CS arising in a borderline endometrioid tumour of the ovary where it merged with squamous metaplasia.. This observation illustrates another pitfall of CS which can be misidentified as keratin pearls. The pathogenesis remains unclear but it has been claimed that the accumulation of basement membrane material may be due to the proliferation of pre-existing myoepithelial cells that secrete matrix components. Since ovarian tumours do not contain myoepithelial cells, one should assume that the epithelial cells differentiate towards myoepithelial cells as it has been shown in vitro and ex vivo.

Topics: Adult; Carcinoma, Endometrioid; Collagen; Diagnosis, Differential; Diagnostic Errors; Extracellular Matrix; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Ovarian Cysts; Ovarian Neoplasms; Ovary

To discriminate between adenocarcinomas that are primary to the ovary and metastatic to the ovary, especially of colonic and breast origin, by immunohistochemistry, using stepwise discriminant analysis or a decision tree.. 312 routinely processed, formalin fixed tissue specimens were used. The tumours were divided into a learning set (n = 159), composed of primary tumours of ovary, breast, and colon, and a test set, comprising 134 metastases from these sites and an additional 19 primary ovarian carcinomas. The immunohistochemical panel was composed of antibodies against cytokeratin 7 (CK7) and 20 (CK20), CA125, vimentin, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and the oestrogen receptor (ER). The staining results of the tumours were expressed as the product of the staining intensity and the percentage of positive tumour cells. Analyses were first performed on the learning set and then evaluated on the test set.. Although the immunostaining patterns showed a considerable overlap between the three types of adenocarcinoma, the breast carcinomas were typically positive for GCDFP-15 and often for ER, and negative for vimentin. Ovarian carcinomas were always positive for CK7 and to a lesser extent for CA125. Colonic carcinomas showed prominent positivity for CEA and CK20, while no staining was seen for ER and vimentin. In discriminant analysis, six antibodies (alpha CK7, alpha CK20, alpha CA125, alpha CEA, alpha ER, and alpha GCDFP-15) appeared to be necessary for optimal classification: 89% of the learning set and 82% of the test set were classified correctly. In the decision tree, only four antibodies (alpha CK7, alpha CEA, alpha ER, and alpha GCDFP-15) were used to obtain a correct classification score of 89% for the learning set and 84% for the test set.. Using a semiquantitative assessment of the immunostaining results by a restricted panel of six antibodies with stepwise discriminant analysis, 80-90% of the adenocarcinomas of colon, breast, and ovary can be correctly classified. Discriminant analysis is computer aided and therefore an easy method and for each case a probability value of the classification result is obtained. The intuitive decision tree method provides a slightly better result, requires only four antibodies, and offers a more practical method for the surgical pathologist.

Topics: Adenocarcinoma; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Breast Neoplasms; CA-125 Antigen; Carcinoembryonic Antigen; Carrier Proteins; Colonic Neoplasms; Decision Trees; Diagnosis, Differential; Discriminant Analysis; Female; Glycoproteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Membrane Transport Proteins; Ovarian Neoplasms; Receptors, Estrogen; Vimentin

The technetium Tc 99m-labeled monoclonal antibody MAb-170 was designed for diagnostic use in patients with gynecologic adenocarcinoma. Our investigation was initiated to verify its usefulness for radioimmunoscintigraphy of ovarian tumors.. Most of the 82 patients participating in this study underwent immunoscintigraphy before first-look surgery.. Radioimmunoscintigraphy recognized 36 of 41 patients with adenocarcinoma of the ovaries, corresponding to an overall sensitivity of 88%. Specificity was 90% (38/42). The calculation of accuracy gave a result of 89% (74/83). Of 110 known lesions, 92 were visualized successfully; thus the local-regional sensitivity was 84%. Of 160 benign tumor sites, 154 showed no evidence of tracer accumulation, corresponding to a local-regional specificity of 96%. The smallest lesion visualized was an adenocarcinoma of the corpus uteri with a diameter of 1.5 cm.. The monoclonal antibody MAb-170 is a promising radiopharmaceutical for immunoscintigraphy of ovarian adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Neoplasm; Female; Humans; Immunologic Techniques; Keratins; Middle Aged; Ovarian Neoplasms; Radionuclide Imaging; Sensitivity and Specificity; Technetium

Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens.. We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas.. CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use in distinguishing between these 2 entities.. A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot be distinguished from colonic adenocarcinomas using immunohistochemistry.

Topics: Adenocarcinoma; Antibodies, Monoclonal; CA-125 Antigen; Carcinoembryonic Antigen; Colonic Neoplasms; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms

Relaxin-like factor (RLF), a new member of the insulin-like growth factor family, is a reliable marker for normal Leydig cells in the human postpubertal testis (1). Expression of the RLF gene appears to be developmentally regulated, given that only during puberty is RLF expression up-regulated. We recently demonstrated down-regulation of the human RLF gene in testicular Leydig cell tumors indicating dedifferentiation of the Leydig cells within the tumor (2). Ovarian Sertoli-Leydig cell tumors (SLCTs), histologically typed as androblastomas, are rare, potentially malignant sex-cord stromal tumors exhibiting testicular-like structure and differentiation of various degrees. In the present study, we investigated the expression of RLF, 17alpha-hydroxylase, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), Ki-67, and cytokeratin 18 in a human ovarian SLCT of low differentiation.

Topics: 3-Hydroxysteroid Dehydrogenases; Cell Differentiation; Female; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Insulin; Keratins; Ki-67 Antigen; Middle Aged; Ovarian Neoplasms; Proteins; RNA, Messenger; Sertoli-Leydig Cell Tumor; Steroid 17-alpha-Hydroxylase

Ovarian endometrioid carcinomas with sertoliform features (SECs) are infrequent and often misinterpreted as sex cord-stromal tumors. The clinicopathologic features and immunohistochemical expression of keratin, epithelial membrane antigen (EMA), inhibin, and estrogen and progesterone receptors were evaluated in 13 cases of SEC. The women were 41 to 89 years of age (mean, 60 yr) with abdominal enlargement secondary to a unilateral ovarian mass as the most frequent clinical presentation. One patient displayed virilization. At presentation, 10 patients were Stage I, one was Stage II and two were Stage III. The tumors were composed of compact anastomosing cords and small tubules embedded within a fibrous stroma. Nuclear features were Grade 1 or 2 in all but one tumor. Areas of conventional endometrioid carcinoma were observed in 12 cases. An adenofibromatous component comprising 5 to 60% of the lesion was present in seven cases. All 12 cases examined immunohistochemically were positive for keratin and EMA and negative for inhibin with focal, luteinized stromal cells positive for inhibin in 10 cases. Estrogen and progesterone receptors were positive in 10 and 11 cases, respectively. Follow-up on 6 of 10 patients with Stage I and the one patient with Stage II disease displayed no evidence of disease 10 to 120 months (mean, 57 mo). Progressive disease and death occurred at 12 and 72 months only in the two women with Stage III disease, one of which had an associated serous carcinoma in the contralateral ovary. Adequate sampling, a careful search for areas of conventional endometrioid carcinoma, and immunohistochemical studies (including EMA, keratin, and inhibin) are helpful in the evaluation of ovarian tumors with sex cord-stromal features. SEC should be considered a well-differentiated endometrioid carcinoma despite the presence of a solid, sex cord-like proliferation, with a good prognosis when confined to the ovary.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Inhibins; Keratins; Middle Aged; Mucin-1; Neoplasm Staging; Ovarian Neoplasms; Ovary; Receptors, Estrogen; Receptors, Progesterone; Sertoli Cell Tumor; Sertoli-Leydig Cell Tumor; Sex Cord-Gonadal Stromal Tumors

The expression pattern of the epithelial cell markers MUC1 (CA15-3, EMA), CA125 (OC125), human epithelial antigen HEA (Ber-EP4) and cytokeratins (Ck7, Ck8, Ck7/8, Ck8/18/19) was studied in seven human ovarian cancer cell lines. We analyzed the cell lines by immunofluorescence to determine the surface as well as cytoplasmic expression. Furthermore, we evaluated the mRNA expression of MUC1, Ck18 and Ck19 by reverse transcriptase-polymerase chain reaction (RT-PCR). All cell lines were positive for MUC1. However, expression patterns and staining intensity depended on the different epitope-specific antibodies. CA125, a typical serum marker for ovarian carcinomas, was positive only in two cell lines. HEA was strongly positive in three cell lines, whereas the others expressed the antigen only weakly in the cytoplasm. Ck7 was not expressed in three of the seven cell lines. Ck7/8 was detectable in all cell lines and was strongly expressed in four of them. MUC1 mRNA was expressed by all cell lines as detected by RT-PCR. These findings permit selection of a suitable marker for the detection of disseminated ovarian cancer cells.

Topics: Antigens, Neoplasm; CA-125 Antigen; Epithelial Cells; Female; Flow Cytometry; Fluorescent Antibody Technique; Humans; Keratins; Mucins; Ovarian Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured

An ovarian mucinous cystadenofibroma with peculiar neuroendocrine cell micronests is described in a 59-year-old Japanese woman. Aggregates of epithelial cells resembling microinvasive carcinoma cells were scattered throughout the adenofibromatous area. These micronests were composed of small uniform cells with argentaffin and argyrophil granules. Numerous small cells with neuroendocrine granules were also seen within mucinous glands. This is the first report of neuroendocrine micronests in an ovarian neoplasm, a finding that should be distinguished from microinvasion.

Topics: Adenofibroma; Chromogranin A; Chromogranins; Cystadenoma, Mucinous; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasm Invasiveness; Neurosecretory Systems; Ovarian Neoplasms

To illustrate unusual patterns of isolated supradiaphragmatic presentation and relapse of papillary serous adenocarcinoma of the ovary.. Retrospective study of five women (26-57 years) managed by a specialist gynaecological oncology unit.. Three women relapsed in the neck, mediastinal or axillary nodes 3 to 5 years after complete abdomino-pelvic remission. Two women presented with pleural or cervical lymph node metastases respectively 2 and 13 years before the primary pelvic tumour was discovered. Clinical presentations in these five women mimicked metastatic thyroid and breast cancer and mesothelioma. In four of the five woman supradiaphragmatic nodal disease was heavily calcified.. Women with papillary serous ovarian cancer may develop supradiaphragmatic disease without evidence of peritoneal metastasis or primary pelvic tumours. Isolated supradiaphragmatic relapse may occur many years after complete remission of abdomino-pelvic disease. Calcification in supradiaphragmatic lymph nodes should not be assumed to be due to old granulomatous disease as this may be the only clue to relapsing disease. Review of prior histology and use of immunohistochemical stains were valuable in diagnosis of these cases.

Topics: Adult; Axilla; Biomarkers, Tumor; CA-125 Antigen; Calcinosis; Clavicle; Cystadenocarcinoma, Papillary; Female; Humans; Keratin-7; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neck; Ovarian Neoplasms; Radiography; Retrospective Studies

We report a series of 41 ovarian metastases from colorectal adenocarcinomas. The patients'mean age was 57.1 years at the time the metastasis was discovered, and 55.8 years at the time the primary carcinoma was found. The diagnosis of the primary tumour was anterior to the metastasis in 25 cases (mean interval 21 months), simultaneous in 13 and posterior in 3 others. The metastases formed cystic and solid masses with a mean weight of 330 g. The endometrioid architectural type was the most frequent, either pure (71%, 29/41) or associated with a mucinous component (17%, 7/41). Pure mucinous or other architectural types were rare. The endometrioid type was characterized by glands with a garland pattern, and intraluminal dirty tumoral necrosis. Immunohistochemistry helped to distinguish the metastases of endometrioid type from serous or endometrioid primary ovarian carcinoma; 71% of the former were CK7(-)/CK20(+), and 100% of the latter had the reverse profile CK7(+)/CK20(-).

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Endometrioid; Colorectal Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratins; Middle Aged; Ovarian Neoplasms; Time Factors

Recently, there has been significant effort in developing techniques designed to detect disseminated tumor cells in the peripheral blood (PB). These techniques include immunocytochemical staining of cytocentrifuge slides, flow cytometry, and RT-PCR. Several authors reported various results concerning the sensitivity of the detection limit when applying these methods. The aim of this study was to assess the value of two methods in the detection of ovarian carcinoma cells in the PB. For tumor cell detection we compared RT-PCR to immunomagnetic enrichment followed by flow cytometric analysis. In a model system, single cell suspensions of ovarian cancer cell lines were mixed with full blood samples from healthy donors in order to determine the sensitivity limit of the two methods and to analyze the reproducibility of each. In a multiparameter flow cytometric analysis, tumor cells were defined as cytokeratin 7/8 positive and CD45 negative. RNA was screened for MUC1 mRNA by RT-PCR. MUC1 mRNA expression turned out not to be a specific marker of disseminated ovarian cancer cells, because a weak expression was also found in samples of healthy persons. Using immunomagnetic enrichment followed by flow cytometry, one carcinoma cell per 1 x 10(6) leukocytes was detectable. However, a minimum of 10 ml blood had to be analyzed in order to clearly distinguish real positive tumor cells from false-positive signals.

Topics: Biomarkers, Tumor; Carcinoma; Evaluation Studies as Topic; Female; Flow Cytometry; Humans; Keratins; Leukocyte Common Antigens; Mucin-1; Ovarian Neoplasms; Phycoerythrin; Reverse Transcriptase Polymerase Chain Reaction

Little is known about the factors regulating epithelial ovarian cancer cell growth. This is due, in large part, to the difficulty in obtaining and culturing human ovarian cells for relevant in vitro studies. We recently developed a method for culturing epithelial carcinoma cells derived from fresh, untreated epithelial ovarian cancer specimens. The cell populations are free of fibroblasts and reflect the primary tumor as determined by chromosomal analysis. In this study we report on the cells' growth in serum-free medium and their secretion of CA-125, a glycoprotein marker for ovarian cancer. Furthermore we characterize the insulin-like growth factor (IGF) system in these primary ovarian carcinoma cell cultures. The cells secrete IGF peptides and IGF-binding proteins, possess specific type I IGF receptors, and respond to exogenous IGFs. The culture system reported here provides the basis for further study and manipulation of the IGF system as well as other regulators of epithelial ovarian cancer. Greater understanding of the cellular and molecular mediators of primary human ovarian cancer cell growth may translate into relevant clinical interventions.

Topics: Adenocarcinoma; CA-125 Antigen; Cell Division; Culture Media, Conditioned; Culture Media, Serum-Free; Female; Humans; Insulin-Like Growth Factor Binding Proteins; Keratins; Ovarian Neoplasms; Receptor, IGF Type 1; RNA, Messenger; RNA, Neoplasm; Somatomedins; Tumor Cells, Cultured; Vimentin

Ovarian sex cord-stromal tumors are a morphologically diverse group of neoplasms that can mimic the appearance of other ovarian tumors. Because the treatment and prognosis of sex cord-stromal tumors differs substantially from those of other ovarian neoplasms, the development of an immunohistochemical panel to support the diagnosis of the former group of tumors would be useful. In this report, the utility of immunostaining for inhibin alpha, epithelial membrane antigen, MIC2 gene protein product, and keratin in the differential diagnosis of sex cord-stromal tumors was assessed in formalin-fixed, paraffin-embedded sections. In addition, the immunohistochemical staining pattern of ovarian small cell carcinomas (SCCs), hypercalcemic type, was analyzed in an attempt to clarify the histogenesis of these tumors. Thirty-two (97%) of 33 granulosa cell tumors (GCTs), 10 (91%) of 11 Sertoli-Leydig cell tumors (SLCTs), and 4 (8%) of 51 carcinomas showed inhibin alpha immunopositivity. None of the 3 lymphomas, 5 carcinoids, 6 dysgerminomas, or 12 SCCs showed inhibin alpha positivity. Eighteen (55%) GCTs, 6 (55%) SLCTs, 6 (12%) carcinomas, and 7 (58%) SCCs showed MIC2 gene expression. None of the GCTs and only one SLCT showed epithelial membrane antigen (EMA) positivity, although 92% of surface epithelial carcinomas and 75% of SCCs were immunoreactive. These data suggest that detection of inhibin immunoreactivity in an ovarian tumor that is EMA-negative provides both sensitive and specific support for the diagnosis of a sex cord-stromal tumor. Because SCCs generally stain for EMA but not for inhibin, it appears that SCCs probably represent a variant of surface epithelial tumor rather than a type of sex cord-stromal tumor.

Topics: 12E7 Antigen; Antigens, CD; Biomarkers, Tumor; Carcinoma, Small Cell; Cell Adhesion Molecules; Diagnosis, Differential; Female; Granulosa Cell Tumor; Humans; Hypercalcemia; Immunohistochemistry; Inhibins; Keratins; Mucin-1; Ovarian Neoplasms; Sertoli-Leydig Cell Tumor; Sex Cord-Gonadal Stromal Tumors

Serum assays for CA 125 are often used in the diagnosis and follow-up of patients with gynecologic neoplasms. A case of a 34-year-old woman with desmoplastic small round cell tumor (DSRCT) having an unusual morphology, including the presence of a signet ring cell component, and high serum CA 125 levels that was initially diagnosed as poorly differentiated carcinoma of the ovary is herein reported. Ultrastructurally, the signet ring appearance was shown to be the result of either the presence of intracytoplasmic vacuoles or dilatation of the intercellular space. Immunoperoxidase staining showed strong reactivity for desmin, keratin, vimentin, and CA 125. Immunohistochemical studies were performed on six additional DSRCTs but only two showed focal staining for CA 125. Because the patient's CA 125 serum level decreased after she received chemotherapy and her tumor was removed, and it became elevated again when the disease recurred, it is possible that CA 125 could be used as a marker of persistent and recurrent disease in those uncommon cases of DSRCT in which there are elevated serum levels of this marker at the onset of treatment.

Topics: Adult; CA-125 Antigen; Carcinoma, Signet Ring Cell; Carcinoma, Small Cell; Desmin; Fatal Outcome; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Recurrence, Local; Ovarian Neoplasms; Vimentin

Adenocarcinomas may arise primarily from the urinary bladder, but secondary involvement from adenocarcinomas arising in adjacent organs is more common. In the present study we tried to differentiate primary urinary bladder adenocarcinomas from adenocarcinomas arising from the surrounding organs, based on their antigen profiles in routinely processed, paraffin-embedded tissue specimens. We analysed the staining results using stepwise linear discriminant analysis.. We investigated the usefulness of a panel of antibodies against cytokeratin 7, E48, cytokeratin 20, PSA, PSAP, CEA, vimentin, OC125 and HER-2/neu, to discriminate primary bladder adenocarcinoma from adenocarcinomas arising from the prostate, urachus, colon, cervix, ovary and endometrium. In the differential diagnosis with urinary bladder adenocarcinoma, an overall correct classification was reached for 77% and 81% of urachal and colonic carcinomas, respectively, using CEA, for 93% of prostatic adenocarcinomas using PSA, for 82% and 70% of cervical and ovarian adenocarcinomas, respectively, using OC125, and for 91% of endometrial adenocarcinomas using vimentin. Adding other antibodies did not improve the classification results for any of these differential diagnoses.. For the surgical pathologist, a panel of antibodies consisting of CEA, PSA, OC125 and vimentin is helpful to differentiate primary urinary bladder adenocarcinomas from adenocarcinomas originating from prostate and endometrium, less helpful in differentiation with urachal carcinoma, and not helpful in differentiation with colonic, cervical and ovarian carcinoma.

Topics: Abdominal Neoplasms; Acid Phosphatase; Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Papillary; Cell Adhesion Molecules; Diagnosis, Differential; Endometrial Neoplasms; Female; Glycoproteins; GPI-Linked Proteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Neoplasms, Unknown Primary; Ovarian Neoplasms; Prostate; Prostate-Specific Antigen; Receptor, ErbB-2; Urachus; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; Vimentin

The present report of a 25 year old woman with a primary ovarian angiosarcoma is supplemented by histochemical and ultrastructural studies and reviews the literature of this extremely rare neoplasm. Since this ovarian tumor, especially in young women, may constitute a diagnostic pitfall, problems relating to differential diagnosis are emphasized. Although the origin of this neoplasm appears to occur most likely from the rich ovarian vasculature, other less conventional histogenetic theories such as a possible origin in mixed mullerian tumor, in teratoma or in other ovarian germ cell tumors have also been proposed and are considered in this paper.

Topics: Actins; Adult; Carcinoma, Embryonal; Cytoplasmic Granules; Diagnosis, Differential; Factor VIII; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Ovarian Neoplasms; Platelet Endothelial Cell Adhesion Molecule-1; Sertoli-Leydig Cell Tumor; Vimentin

To discriminate adenocarcinoma metastases originating from either colon or ovary, a panel of immunohistochemical markers was evaluated. For this purpose, paraffin sections from 157 primary and metastatic colonic and ovarian carcinomas were immunostained. These cases were divided into a learning group of 46 colonic and 54 ovarian carcinomas and a test group of 29 colonic and 28 ovarian carcinomas, including all metastatic tumors, among which were five with unknown primary site at the time of testing. The sections were immunostained with antibodies against carcinoembryonic antigen (CEA), cytokeratin 7 (CK7), cytokeratin 20 (CK20), CA125, vimentin, and CA19.9. Staining results were expressed as the product of staining intensity and percentage of positive tumor cells. Stepwise discriminant analysis was applied on the learning set to obtain a classification function for both tumors. The validity of the classification function was evaluated using the test set. There was considerable overlap in immunostaining for both tumor types, but colonic carcinomas were typically positive for CEA and CK20 and negative for CK7 and CA125. Ovarian carcinomas were typically positive for CK7 and CA125 and negative for CEA and CK20. In discriminant analysis, the best combination of markers appeared to be CK7 and CEA. Only one sample of the test group (2%) was misclassified. Taking learning and test groups together, 136 of the 157 samples (87%) were correctly classified with high posterior probability (PP > .8). However, from the 28 mucinous ovarian carcinomas, only 19 (68%) could correctly be classified with high PP. When excluding the nonmucinous ovarian carcinomas from the analysis, overall 87 of 103 (84.5%) of the samples were correctly classified (PP > .8) with a combination of CEA, CK7, and also vimentin. From the 28 mucinous ovarian carcinomas, only two (7%) were misclassified, and four could not be classified with sufficient certainty. In neither analysis did CK20, CA125, or CA19.9 emerge as discriminatory parameters. Based on the same data, an intuitive flow chart was constructed with which 129 of 157 cases could be classified (only one falsely) without further statistical analysis. The five metastases with an at first unknown primary could, according to the follow-up, all be classified correctly with high PP. Most ovarian carcinomas, including the mucinous ones, can be discriminated with high probability from colonic carcinomas using a panel of three antibodies directed

Topics: Adenocarcinoma; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Cell Count; Colonic Neoplasms; Decision Trees; Diagnosis, Differential; Discriminant Analysis; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasms, Unknown Primary; Ovarian Neoplasms; Retrospective Studies; Vimentin

We have investigated the use of inhibin and cytokeratin-7 (CK-7) in distinguishing endometrioid ovarian carcinomas (both typical and sex cord-like) form granulosa cell and Sertoli cell-containing ovarian tumors. Immunohistochemical staining with inhibin, CK-7, and epithelial membrane antigen (EMA) was performed on 6 endometrioid carcinomas simulating sex cord-stromal tumors, 5 typical endometrioid carcinomas, 14 adult granulosa cell tumors (AGCTs), 3 Sertoli-Leydig cell tumors (SCLTs), and 1 sex cord tumor with annular tubules (SCTAT). All AGCTs and SLCTs as well as the SCTAT were inhibin-positive. In contrast, all of the endometrioid carcinomas (both typical and those mimicking sex cord-stromal tumors) were inhibin-negative. CK-7 expression was not observed in the granulosa cell tumors and it was noted only in retiform areas in SLCTs. All 5 typical endometrioid carcinomas and 5 of the 6 sex cord-like endometrioid carcinomas were CK-7 positive. EMA was positive in all carcinomas but negative in the SCTAT, AGCTs, and SLCTs. Inhibin can distinguish between sex cord-stromal tumors (whether granulosa or Sertoli-Leydig type) and endometrioid carcinomas. CK-7 is also helpful in differentiating between AGCTs and most endometrioid carcinomas, and may also aid in separating SLCTs from sertoliform carcinomas. The addition of inhibin to an antibody panel is important because it provides a positively-staining marker for sex cord-derived cells.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Endometrioid; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Inhibins; Keratin-7; Keratins; Middle Aged; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors

Topics: Antigens, Neoplasm; Antigens, Surface; Carcinoma, Squamous Cell; Coloring Agents; DNA, Neoplasm; Female; Flow Cytometry; Humans; Keratins; Neoplasms; Ovarian Neoplasms; Tumor Cells, Cultured

Topics: Endometrial Neoplasms; Female; Foam Cells; Histiocytes; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors

To determine the expression of vimentin and cytokeratin in eutopic and ectopic endometrium of women with both adenomyosis and ovarian endometrioma and to evaluate their cyclic changes during the menstrual cycle.. Twenty patients requiring hysterectomy with salpingo-oophorectomy were studied by immunohistochemistry according to their menstrual cycles.. Cyclic expression of vimentin was noted in eutopic endometrium and adenomyosis, but not in endometrioma. Cytokeratin expression did not change during the menstrual cycles. The mean intensities of epithelial vimentin were significantly different from each other, being the lowest in endometrioma, intermediate in adenomyosis, and the highest in eutopic endometrium. There was no significant difference in intensities of cytokeratin between adenomyosis and endometrioma, but these intensities were significantly lower than that of eutopic endometrium.. Lower intensities of cytokeratin in adenomyosis and endometrioma than in eutopic endometrium suggest that the ectopic endometria may have a lower degree of differentiation regardless of the site. The lower intensity of epithelial vimentin in endometrioma than in adenomyosis during the proliferative phase may reflect decreased functional activity, probably because of a pressure effect on the lining epithelium within the endometrioma.

Topics: Endometrial Neoplasms; Endometriosis; Endometrium; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Menstrual Cycle; Ovarian Neoplasms; Vimentin

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic factor in women with ovarian cancer. To determine the specificity of the M3/M21 test, we investigated M3/M21 serum levels in several benign conditions. This retrospective study comprises 37 patients with ovarian cancer FIGO stages Ia to III. Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases, respectively. With a sensitivity of 57% and a specificity of 95%, M3/M21 is not suitable as a screening marker for ovarian cancer. Although M3/M21 is able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 does not provide information additional to CA 125. M3/M21 serum levels are elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients, elevated M3/M21 serum levels prior to therapy were associated with poor overall and disease-free survival (log-rank test, p = 0.03; log-rank test, p = 0.01, respectively). M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoma; Endometriosis; Epitopes; Evaluation Studies as Topic; Female; Humans; Keratins; Middle Aged; Ovarian Diseases; Ovarian Neoplasms; Pelvic Inflammatory Disease; Retrospective Studies

Differential staining with cytokeratin (CK)-7 and CK-20, two members of a complex family of proteins in human epithelial cells, proved critical in showing that the extremely well-differentiated goblet-cell (intestinal) mucinous epithelium lining the surface of the endometrium and endocervix in two patients and the fallopian tube in one was identical to that of the coincident appendiceal neoplasms. One of these patients also had a large ovarian tumor that grossly and microscopically resembled a mucinous cystadenoma of borderline malignancy and would have been considered primary except for the CK stains (CK-20 positive and CK-7 negative), which suggested metastasis from the appendix, presumably by a transtubal route.

Topics: Appendiceal Neoplasms; Biopsy; Endometrial Neoplasms; Epithelium; Fallopian Tubes; Female; Goblet Cells; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Mucins; Ovarian Neoplasms; Uterine Cervical Neoplasms

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin marker CYFRA 21-1 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic marker in women suffering from ovarian cancer. In order to determine the specificity of the CYFRA 21-1 test, we have investigated CYFRA 21-1 serum levels in several benign conditions. This retrospective study comprises 37 patients suffering from ovarian cancer FIGO stages Ia-III. Sera from patients with benign ovarian cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases respectively. With a sensitivity of 41% and a specificity of 95%, CYFRA 21-1 was not suitable as a screening marker for ovarian cancer. Although CYFRA 21-1 was able to discriminate between ovarian cancer and benign adnexal tumours (univariate regression model, P = 0.0001), CYFRA 21-1 did not reveal additional information to CA 125 in a multivariate regression analysis (P = 0.06). CYFRA 21-1 serum levels were elevated in benign conditions such as liver cirrhosis, but not in endometriosis and inflammatory diseases. In ovarian cancer patients, elevated CYFRA 21-1 serum levels before therapy were associated with a poor overall and disease-free survival (log-rank test, P = 0.02 and log-rank test, P = 0.005 respectively). CYFRA 21-1, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.

Topics: Adnexal Diseases; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Keratin-19; Keratins; Middle Aged; Ovarian Neoplasms; Pelvic Inflammatory Disease; Prognosis; Retrospective Studies; Sensitivity and Specificity

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening, prognostic, and monitoring marker for ovarian cancer and as a predictive marker in patients with adnexal masses. In order to determine the specificity of the M3/M21 test we investigated M3/M21 serum levels in several benign conditions. The cytokeratin tumor markers M3/M21 and Tissue Polypeptide Specific Antigen (TPS) were also investigated in the follow-up of ovarian cancer patients. We evaluated M3/M21 serum levels in 75 patients suffering from ovarian cancer FIGO stages Ia to III, using a prototype immunoradiometric assay (IRMA). Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10, and 20 cases, respectively. Furthermore, we analyzed TPS serum levels by means of IRMA during the follow-up of 40 patients suffering from ovarian cancer. With a sensitivity of 57% and a specificity of 95% M3/M21 was not suitable as a screening marker for ovarian cancer. Although M3/M21 was able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 did not provide additional information (in addition to CA 125) (multivariate logistic regression, p = 0.2). M3/M21 serum levels were elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients elevated M3/M21 serum levels prior to therapy were associated with a poor overall and disease-free survival (log-rank test, p = 0.03, and log-rank test, p = 0.01, respectively). In patients with recurrent ovarian cancer M3/M21 and TPS showed median lead-time effects of 3.2 and 3.9 months, respectively. M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor. M3/M21 and TPS are valuable tumor markers in the follow-up of ovarian cancer patients.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Female; Humans; Keratins; Middle Aged; Neoplasm Staging; Ovarian Cysts; Ovarian Neoplasms; Peptide Fragments; Sensitivity and Specificity; Tissue Polypeptide Antigen

The expression of cholesterol sulfate (CS) is known to increase during squamous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the subsequent expression of transglutaminase-1 (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumorigenesis by CS, we examined the concentration and the potential for synthesis of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established from human uterine cervical cancer patients and compared them for the rate of expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expressed in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, cells derived from a keratinizing type of well-differentiated cervical carcinoma demonstrated strong potential for synthesis of CS, stained positive with anti-cytokeratin antibody, and exhibited a higher specific activity of TG-1, whereas the cells without CS did not stain positive with anti-cytokeratin antibody and exhibited a lower specific activity of TG-1. These findings indicate that CS is coexpressed with TG-1 and cytokeratin in the well-differentiated types of squamous cell cancers as a tumor marker.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cholesterol Esters; Female; Humans; Immunohistochemistry; Keratins; Lipid Metabolism; Lipids; Ovarian Neoplasms; Tumor Cells, Cultured; Uterine Cervical Neoplasms; Uterine Neoplasms

To assess the role of cytokeratin 7 monoclonal antibody in the differential diagnosis of primary ovarian carcinoma and metastatic ovarian carcinoma originated from the gastrointestinal tract.. Immunohistochemical study using cytokeratin 7 monoclonal antibody and ABC kit.. All the 46 cases of primary ovarian carcinoma were CK 7 positive, while in the metastatic ovarian carcinoma of intestinal origin, all cases remained negative for CK7. Half of the 34 cases of metastatic ovarian carcinoma of gastric origin were CK 7 positive. The positive result of CK7 was significantly higher in the primary ovarian carcinoma than in each group of the metastatic ovarian carcinoma (P < 0.001).. CK 7 is seemed to be a useful antibody in the differential diagnosis of ovarian carcinoma.

Topics: Antibodies, Monoclonal; Carcinoma, Endometrioid; Cystadenocarcinoma, Mucinous; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Humans; Intestinal Neoplasms; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms

Topics: Adult; Androgens; Female; Follicle Stimulating Hormone; Granulosa Cell Tumor; Humans; Immunohistochemistry; Keratins; Luteinizing Hormone; Ovarian Neoplasms; Progesterone; Vimentin; Virilism

Transitional cell carcinoma (TCC) is rare in the female genital tract. Although it is most common in the ovary, small series of cases in the cervix have been reported, with isolated cases described in the fallopian tube, adnexa uteri, and endometrium.. Eight cases of primary TCC involving the endometrium and 1 case of ovarian TCC metastatic to the endometrium were retrieved from the files of the Armed Forces Institute of Pathology and the University of Texas Southwestern Medical Center. Cases were selected based on the presence of endometrial TCC, whether pure or combined with other patterns, and regardless of the relative amount. Immunostaining for cytokeratins 7 and 20 was performed.. Among the 8 women with primary endometrial tumors, the mean age was 61.6 years (range, 41-83 years). Uterine bleeding was the presenting symptom in 7 women. Macroscopically, the tumors were polypoid, and infiltrated the myometrium, although the extent of infiltration varied. Seven endometrial tumors showed a papillary component. TCC was always admixed with other patterns (predominantly squamous, but also endometrioid, papillary, and serous patterns), with the proportion of the TCC component ranging from 5% to 95% (mean, 63.8%). TCC was the main invasive pattern observed in all three of the cases that had deep myometrial invasion; these cases also had vascular invasion. Seven tumors were confined to the uterus; one was metastatic to the ovary. The ovarian TCC metastatic to the endometrium had a pure TCC pattern. Five of 7 cases of TCC had cytokeratin 7+/20- immunoreactivity; 2 cases were cytokeratin 7-/20-. Treatment of primary endometrial tumors was mainly surgical, with adjuvant radiation therapy in 4 cases or chemotherapy in 1 case. Survival ranged from 3 months to 12.9 years (mean, 5.1 years). Of five women for whom follow-up was available, three were alive with no evidence of disease, one was alive with a local recurrence, and one died of unrelated disease.. TCC is a rare, distinct subtype of endometrial carcinoma with morphologic features of urothelial differentiation, but retention of a mullerian immunoprofile. While the overall prognosis does not appear to be worse than what might be anticipated for the stage of tumor present, TCC appears to be the more aggressive histologic subtype among the patterns with which it is admixed.

Topics: Adult; Aged; Aged, 80 and over; Blood Vessels; Carcinoma, Transitional Cell; Cell Differentiation; Chemotherapy, Adjuvant; Diagnosis, Differential; Endometrial Neoplasms; Female; Follow-Up Studies; Humans; Hysterectomy; Keratins; Middle Aged; Myometrium; Neoplasm Invasiveness; Ovarian Neoplasms; Ovariectomy; Radiotherapy, Adjuvant; Survival Rate; Uterine Hemorrhage

Intratesticular Müllerian papillary serous tumors lacking stromal invasion are uncommon neoplasms whose immunophenotypic properties have not been studied extensively. We present such information here and compare it with information from a group of ovarian papillary serous tumors of low malignant potential ("borderline serous tumors") that are morphologically identical. We compared the histologic features of our index case of intratesticular Müllerian papillary serous tumor with those of nine ovarian papillary serous tumors. We then evaluated both the index case and the ovarian tumors with antibodies against carcinoembryonic antigen, LeuM1, CA125, estrogen receptors, progesterone receptors, cytokeratin 7, and cytokeratin 20, by use of established immunohistochemical techniques. The testicular and ovarian tumors were morphologically indistinguishable. The intratesticular Müllerian papillary serous tumor expressed LeuM1, CA125, estrogen receptors, progesterone receptors, cytokeratin 7, and weak cytokeratin 20; carcinoembryonic antigen was not expressed. All of the ovarian papillary serous tumors expressed CA125, estrogen receptors, and cytokeratin 7. Eight of nine expressed progesterone receptors. Five of nine stained with LeuM1. Two of nine were focally weakly positive with cytokeratin 20. LeuM1 expression helps distinguish testicular papillary serous tumors from mesothelial proliferations, which might seem morphologically similar. The immunophenotype of intratesticular and female genital papillary serous tumors is similar; this similarity extends to expression of estrogen and progesterone receptors, which is rare in neoplasms in men, especially among testicular neoplasms.

Topics: Aged; Biomarkers; CA-125 Antigen; Cystadenocarcinoma, Papillary; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Lewis X Antigen; Male; Orchiectomy; Ovarian Neoplasms; Receptors, Estrogen; Retrospective Studies; Testicular Neoplasms

A cell line was established from a mixed mullerian tumor of the ovary and designated LN1. Histopathologic analysis of the fresh tumor specimen demonstrated a highly aneuploid heterologous tumor comprised of undifferentiated mesodermal components with carcinomatous cells present as a smaller population. Long-term in vitro culture resulted in the establishment of a cell line that exhibits an epithelial-like morphology and expresses epithelial antigens cytokeratin, epithelial membrane antigen, and carcinoma antigen TAG-72. These cells also express mesenchymal intermediate filaments, vimentin, and desmin. Karyotypic analysis revealed a basic triploid pattern with multiple chromosomal abnormalities, most notably an isochromosome of the short arm of five present in three copies. Analysis of oncogene expression revealed that LN1 cells constitutively express mRNA for c-ras, c-erbB2, and p53. The expression of mRNA for cellular oncogenes correlated with the presence of corresponding oncoproteins, p21H-ras, p21K-ras, and p185erB2 and mutant p53 protein. In summary, coexpression of epithelial and mesenchymal antigens by LN1 cells lends support to the hypothesis that epithelial and mesenchymal elements comprising mixed mullerian tumors of the ovary are derived from a common stem cell precursor. Furthermore, this cell line represents a functional in vitro model to evaluate the biologic activities of these unusual and highly aggressive ovarian malignancies.

Topics: DNA, Neoplasm; Female; Humans; Keratins; Mixed Tumor, Mullerian; Oncogenes; Ovarian Neoplasms; Tumor Cells, Cultured; Vimentin

Unclassified sex cord-stromal tumors (SCSTs) of the testis comprised predominantly of spindle cells can be difficult to classify. To achieve better definition of these tumors, we examined the histologic, histochemical, and ultrastructural features of four unclassified SCSTs with spindle-cell features, and compared their immunohistochemical features with those of 24 other SCSTs of the testis and ovary. Three of the spindle-cell tumors were composed of relatively short spindled cells with prominent nuclear grooves and intermixed epithelioid cells. All of the three were located adjacent to the rete testis. The fourth case consisted of elongate spindle cells that were reminiscent of smooth muscle. In all of the four cases, reticulin enveloped aggregates of cells of various sizes but not individual cells. Ultrastructural analysis of two of the spindle-cell tumors revealed desmosomes, numerous thin filaments, and focal dense-bodies. Immunohistochemically, all of the four tumors were reactive for S-100 protein and smooth muscle actin. Staining for S-100 protein and smooth muscle actin was also observed in three of six granulosa cell tumors and both juvenile granulosa cell tumors. Although variable staining for S-100 protein was found in 5 of the 12 other SCSTs (4 Leydig cell, 6 Sertoli-Leydig cell, and 2 unclassifiable ovarian SCSTs), reactivity for smooth muscle actin was present in only 1 Sertoli-Leydig cell tumor. In contrast, all of the four ovarian fibromas/thecomas were reactive for smooth muscle actin but failed to stain for S-100 protein. Taken together, the histologic, histochemical, immunohistochemical, and ultrastructural features of the spindle-cell tumors are similar to those of granulosa cell tumors. Reactivity for S-100 protein and smooth muscle actin is characteristic of these tumors. These tumors should be distinguished from other unclassified SCSTs.

Topics: Actins; Adult; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Ovarian Neoplasms; S100 Proteins; Sex Cord-Gonadal Stromal Tumors; Testicular Neoplasms

Recently, Frey (Cytometry 17:310-318, 1994) demonstrated that TO-PRO-3 iodide (TP3) can be excited indirectly by a 488 nm laser line through energy transfer by propidium iodide (PI). In the present study, we investigated whether PI-TP3 energy transfer can help to overcome spectral cross talk problems associated with the combined use of fluorescein isothiocyanate (FITC), R-phycoerythrin (PE), and PI. Mixtures of keratin 8/18 FITC-labeled, keratin 8/18-PE-labeled, and unlabeled MCF-7 breast carcinoma cells were prepared and stained for DNA with PI (100 microM). The effect of adding a range of TP3 concentrations (0.001 to 16 microM) to these mixtures was evaluated. The combined use of PI and TP3 was further evaluated using mixtures of unlabeled and p53 FITC-labeled COV362.cl4 ovarian cancer cells and mixtures of unlabeled and p53 FITC-labeled COV362.cl4 cells and peripheral blood lymphocytes (PBL), additionally stained for keratin 8/18 (PE). Finally, a human ovarian ascites tumor specimen was triple-stained for keratin 8/18 (PE), vimentin (FITC) and DNA or keratin 8/18 (PE), PCNA (FITC) and DNA. Addition of TP3 allowed complete correction for spectral cross talk of PE/PI into the green fluorescence detector (FL1). Only minimal (FL1 - %FL2) compensation was required at a TP3 concentration of 2.0 microM in the presence of PI (100 microM). The PI spectral cross talk into the orange fluorescence detector (FL2) was reduced by about 50% using the same photomultiplier (PMT) settings. Although addition of TP3 reduced the signal-to-background ratio by about 30%, the advantage gained through full compensation for spectral cross talk resulted in an improved discrimination of p53-positive and -negative subpopulations in a mixture of human PBL and COV362.cl4 cells. Furthermore, vimentin-negative and PCNA-negative cells were better resolved in a human DNA-aneuploid ovarian ascites tumor after staining the DNA with PI/TP3, rather than with PI alone. We conclude that the addition of TP3 to PI improves the combined measurement by single-laser flow cytometry of DNA-ploidy and antigen expression in heterogenous clinical samples.

Topics: Antigens; Ascites; Carbocyanines; DNA, Neoplasm; Energy Transfer; Female; Flow Cytometry; Fluorescent Dyes; Humans; Keratins; Lasers; Ovarian Neoplasms; Ploidies; Propidium; Titrimetry; Tumor Cells, Cultured

Cytokeratin 7 (CK-7) has been shown to be uncommonly expressed in colonic epithelial tumors, as opposed to ovarian epithelial tumors, which are always CK-7 positive. The authors investigated the expression of CK-7 in 17 appendiceal cystadenomas and carcinomas, 20 mucinous borderline tumors of the ovary, 10 cases of simultaneous mucinous tumors of the appendix and ovary, three so-called high-stage mucinous borderline tumors of the ovary, and three cases of pseudomyxoma peritonei (PP) of unknown origin. Nine appendiceal cystadenomas were CK-7 negative; two of these were associated with PP, and the peritoneal lesions were negative as well. Three cystadenomas were CK-7 positive. Three appendiceal carcinomas were CK-7 negative, and in one case the metastases were also negative. Two carcinomas were CK-7 positive. All 20 ovarian borderline tumors were CK-7 positive. Six cases of simultaneous mucinous tumors of the ovary and appendix were CK-7 negative, as were their peritoneal mucinous deposits. Four cases showed a positive reaction in both appendiceal and ovarian sites. Two of three so-called high-stage ovarian borderline tumors were CK-7 negative. All three cases of PP of unknown origin were CK-7 negative. In conclusion, appendiceal cystadenomas are often CK-7 negative, whereas ovarian mucinous borderline tumors are always CK-7 positive. The concordant staining pattern for CK-7 of simultaneous mucinous tumors involving the appendix and ovary (60% of which were CK-7 negative) supports an appendiceal origin for these tumors. Our results also support an appendiceal (or colonic) source for any CK-7-negative mucinous tumor involving the ovary or the peritoneum. Furthermore, our findings are in agreement with the assumption that mucinous borderline-like tumors in the ovary associated with PP are not ovarian in origin but are often, if not always, metastatic from an appendiceal (or other) mucinous tumor.

Topics: Adult; Aged; Aged, 80 and over; Appendiceal Neoplasms; Carcinoma; Cystadenocarcinoma; Female; Humans; Keratins; Male; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Pseudomyxoma Peritonei

Human ovarian malignancies from three different patients (histology: two serous cystadenocarcinomata and one mixed Müllerian tumor, homologous type) were successfully serially transplanted intraperitoneally into severe combined immunodeficient (SCID) mice where the tumor cells spread around the peritoneal cavity. If the ascites derived from cystadenocarcinoma cells engrafted in the female genital tract of the SCID mice, they formed cystic tumors resembling remarkably well the original tumors in the patients. Immunohistochemical analysis revealed that the immunophenotype of the patients' original tumor and those grown in SCID mice were similar in the case of the two cystadenocarcinomata; in addition, the marker expression in general was stable during serial transplantation. If distant metastases occurred in the lungs, they immunophenotypically resembled those grown intraperitoneally. In contrast, the cells derived from the mixed Müllerian tumor shifted during serial transplantation from a spindle cell morphology toward a morphology characterized by cuboidal cells. The transition toward a more epithelial phenotype was accompanied by a changed immunophenotype of the tumor cells which became positive for epithelial cell markers such as carcinoembryonic antigens, CA 19-9 and CA 125. Concurrently with this differentiation, the p53 immunophenotype changed from positive to negative, indicating a further mutation in the p53 gene during serial passages.

Topics: Animals; Biomarkers, Tumor; Cystadenocarcinoma; Female; Humans; Keratins; Mice; Mice, SCID; Middle Aged; Mixed Tumor, Mullerian; Ovarian Neoplasms; Phenotype; Uterine Neoplasms

Six permanent human ovarian carcinoma cell lines (OVISE, OVTOKO, OVMANA and OVSAYO from clear cell adenocarcinoma, and OVSAHO and OVKATE from serous papillary adenocarcinoma) were established from solid tumours. The cell lines have been in culture for 5-8 years, the passage number varying from 62 to 246. Immunohistochemical analysis has shown that five of the six cell lines express at least six cytokeratin (CK) polypeptides. OVISE and OVSAYO expressed CKs 6, 7, 8, 18, 19 and 15 and/or 16. OVTOKO was positive for CKs 7, 8, 18, 19 and 15 and/or 16. OVSAHO expressed CKs 6, 7, 8, 14, 18, 19 and 15 and/or 16. OVMANA expressed CKs 6, 7, 8, 18, 19, 20 and 15 and/or 16. OVKATE expressed CKs 6, 7, 8, 13, 17, 18, 19, 20 and 15 and/or 16. The expression of CK7, additional expression of vimentin, and clinical and histopathological findings enabled us to confirm that six cell lines had been established from primary ovarian cancers. Two of the six cell lines were positive for CK20, although CK20 was not expressed in the original tumours. The heterotransplanted tumours produced by CK20-positive cells also expressed CK20. This is the first report of ovarian carcinoma cell lines that express CK20 irrespective of their histological type. CK20 has been found in all colon carcinoma cell lines, but only in the mucinous type of ovarian tumours. These new ovarian carcinoma cell lines will therefore provide a relevant experimental system for elucidating the regulatory control mechanisms of intermediate filament expression.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Papillary; Animals; Biomarkers, Tumor; Female; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratin-20; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Tumor Cells, Cultured

Twenty cases of ovarian metastases derived from appendiceal adenocarcinomas were analyzed. The most common presentation was a pelvic mass. The appendiceal and ovarian tumors were diagnosed concurrently in 15 cases; in the remaining five, the ovarian tumors were diagnosed before the appendiceal tumor. The appendiceal adenocarcinomas demonstrated four morphologic patterns: 1) signet ring cell type, with or without glandular or goblet cell differentiation (14 cases); 2) mixed signet ring cell and intestinal type (two cases); 3) intestinal type (two cases); and 4) typical colorectal type (two cases). The ovarian tumors were bilateral in 16 cases and were histologically similar to the associated appendiceal tumor in each case. Ovarian metastases that demonstrate signet ring cell, glandular, and goblet cell differentiation mimic metastases from gastric adenocarcinoma. Those that are derived from well-differentiated mucinous appendiceal adenocarcinomas mimic primary ovarian mucinous tumors and metastases from the pancreas and biliary tract. Metastases of appendiceal adenocarcinomas of colorectal type simulate both metastatic colorectal carcinoma and primary ovarian endometrioid carcinomas. The appendiceal and ovarian tumors were immunophenotypically identical in each case. Approximately 50% of the appendiceal and ovarian tumors were positive for cytokeratin 7 (CK 7), and all were positive for cytokeratin 20 (CK 20). CK 20 positivity of the ovarian tumors is consistent with gastrointestinal origin; CK 7 positivity does not confirm ovarian origin, because appendiceal carcinomas are positive in 50% of cases. Metastatic appendiceal adenocarcinoma should be considered in the differential diagnosis of mucinous ovarian tumors with signet ring cell, goblet cell, or intestinal type differentiation, especially when these tumors are associated with extraovarian disease and are bilateral.

Topics: Adenocarcinoma; Adult; Aged; Appendiceal Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Middle Aged; Ovarian Neoplasms

Sertoli-Leydig cell tumors (SLCT) are rare sex-cord stromal tumors of the ovary composed of undifferentiated gonadal stromal cells, Leydig cells (LC), and Sertoli cells (SC), with the latter forming structures resembling fetal testicular tubules. The histogenetic basis of morphological male differentiation patterns in females is controversial. Here, we report a SLCT with intermediate differentiation in a 23-year-old woman investigated by light microscopy, immunohistochemistry for intermediate filaments, and sex steroid hormone receptors (SSHR), as well as by polymerase chain reaction (PCR) for the presence of the sex-determining region Y gene (SRY). Our investigation shows that the SCs of SLCT express progesterone and androgen receptors as well as cytokeratins and vimentin. By PCR, SLCT-derived genomic DNA lacked the SRY gene, indicating that the SLCT results from a SRY gene-independent pathway of pseudomale gonadal differentiation. The expression of progesterone receptors (PRs) in the SCs of the SLCT is in contrast to their absence in testicular SCs, but in line with their presence in ovarian granulosa and surface epithelial cells. Thus, our results provide strong evidence for a close histogenetic relationship between the SLCT and the female gonocyte-supporting cell, the granulosa cell (GC).

Topics: Adult; DNA Primers; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Nuclear Proteins; Ovarian Neoplasms; Polymerase Chain Reaction; Receptors, Progesterone; Sertoli-Leydig Cell Tumor; Sex Determination Processes; Sex Differentiation; Sex-Determining Region Y Protein; Transcription Factors; Vimentin

Cytokeratins are polypeptides that constitute a subclass of intermediate filaments in epithelial cells. The aim of the present study was to evaluate the clinical usefulness of the serum evaluation of M3/M21 in patients with ovarian cancer. This retrospective study comprises 75 patients suffering from ovarian cancer FIGO stages Ia-III. M3/M21 reached a sensitivity of 78%, a specificity of 85%, a PPV of 89% and a NPV of 83% using a cut-off level of 45 U 1(-1). Forty-four women developed recurrent disease after complete remission during the observation period. M3/M21 showed lead time effects in 19 patients, ranging from 2 to 8 months (median 3.2 months). Elevated M3/M21 serum levels before therapy were associated with a poor overall survival (log-rank test, P = 0.02). Considering these preliminary results, the value of M3/M21 as a serum tumour marker, i.e. to evaluate the tumour burden, seems promising.

Topics: Adult; Aged; Biomarkers, Tumor; Female; Humans; Keratins; Middle Aged; Ovarian Neoplasms; Retrospective Studies

The immunohistochemical diagnosis between epithelial mesothelioma and adenocarcinoma is currently based on the use of a panel of antibodies to adenocarcinoma-associated antigens and a few antibodies to mesothelial-associated antigens. Since the introduction of epitope retrieval methods, the sensitivity of many antibodies has been enhanced. Thus, a reevaluation of the mesothelioma/adenocarcinoma diagnostic panel becomes necessary. We studied 268 paraffin-embedded formalin-fixed tumor samples that included 57 epithelial mesotheliomas and 211 adenocarcinomas of various origins, comparing an extensive antibody panel with and without heat-induced epitope retrieval (HIER). Marked increase in the sensitivity of several antibodies, with no loss of specificity, was found when HIER was used. After statistical analysis, the antibodies to the epithelial glycoproteins carcinoembryonic antigen, BerEp4, and Bg8 emerged as the best discriminators between adenocarcinoma and epithelial mesothelioma within the entire panel. The mesothelium-associated antibodies, HBME-1, calretinin, and thrombomodulin were less sensitive and less specific than the former, although they were found to be useful on certain cases. Antibodies to cytokeratins and vimentin, although of minor diagnostic value in this context, may be helpful to evaluate the quality of antigen preservation. This study confirms the value of immunohistochemistry to accurately distinguish mesothelioma from adenocarcinoma when an antibody panel approach is used. The addition of heat-induced epitope retrieval methods increases the effectiveness of the procedure and is recommended for most of the antibody panel members.

Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Calbindin 2; Carcinoembryonic Antigen; Colorectal Neoplasms; Decision Trees; Diagnosis, Differential; Epitopes; Female; Hot Temperature; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms; Pleural Neoplasms; Retrospective Studies; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thrombomodulin; Vimentin

Carcinomas metastatic to the ovary are often difficult to distinguish from primary ovarian carcinomas. Adenocarcinoma of the colon may simulate both primary endometrioid and mucinous ovarian tumors. The histologic finding of "dirty" necrosis in association with a "garland" or cribriform pattern has been suggested as a useful feature in distinguishing metastatic colonic carcinomas from primary endometrioid ovarian carcinomas. This study was performed to determine the use of "dirty" necrosis in distinguishing primary ovarian carcinoma from metastatic colonic carcinoma by studying 71 of the former and 10 of the latter. At least focal dirty necrosis was found in 68% of primary ovarian epithelial cancers, including 92% of the endometrioid subtype, and in 100% of the metastatic colonic carcinomas. A subgroup of cases was evaluated immunohistochemically using cytokeratin (CK) 7, CK 20 and carcinoembryonic antigen (CEA). The phenotype of CK 7 +/CK 20-/CEA-was present in 92% of primary ovarian carcinomas studied, whereas, 90% of metastatic colonic carcinomas were CK 7-/CK 20 +/CEA+. The finding of dirty necrosis is not specific for metastatic colonic cancer, and differential cytokeratin immunostaining is a useful adjunct in this differential diagnosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Middle Aged; Necrosis; Ovarian Neoplasms

A 55-year-old woman, who was found to have malignant squamous cells on a routine cervical smear, underwent a conization biopsy, followed by hysterectomy with bilateral salpingo-oophorectomy. No gross tumor was present in the uterus, but both ovaries, which were of normal size, contained multiple cysts filled with light brown, soft material. Microscopic examination showed squamous cell carcinoma in situ of the cervix with contiguous spread to the endometrium, fallopian tubes, and ovaries; squamous cell carcinoma extensively replaced the endometrial and tubal epithelium, focally invaded the wall of the fallopian tubes, and involved the parenchyma of both ovaries. Although an invasive cervical carcinoma occasionally spreads to the ovary, this case illustrates that exceptionally an in situ tumor spreads along the epithelium of the upper genital tract and the ovarian surface and invades the ovary and tubes. The detection of human papillomavirus DNA in the cervical, endometrial, tubal, and ovarian tumors by the polymerase chain reaction suggests a role for human papilloma virus infection in this case.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Endometrial Neoplasms; Fallopian Tube Neoplasms; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Middle Aged; Ovarian Neoplasms; Papillomaviridae; Uterine Cervical Neoplasms

To cast light on the capacity of an ovarian adenocarcinoma to undergo irreversible cellular differentiation, we established clonal cell lines from cultured ovarian carcinoma cells treated with sodium butyrate and examined their phenotypic changes.. The poorly differentiated ovarian carcinoma cell line AMOC-2 was exposed to 2 mM sodium butyrate for 30 days, and clonal cell lines were established by a dilution plating technique.. Five clonal cell lines were established. One of them had a longer doubling time and lower plating efficiency than the parental clone, also demonstrating stronger expression of vimentin and 56 kD cytokeratin. This clone became columnar with pronounced polarity, formed gland-like structures when cultured in collagen gels, and exhibited no tumorigenicity, in contrast to the parental clone.. Sodium butyrate treatment of AMOC-2 cells can cause phenotypic changes reminiscent of maturation in the Müllerian duct, endocervix, and/or endometrium.

Topics: Adenocarcinoma; Animals; Blotting, Western; Butyrates; Butyric Acid; Cell Count; Cell Differentiation; Cell Division; Collagen; Culture Media; Female; Humans; Keratins; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Time Factors; Tumor Cells, Cultured; Vimentin

The histologic distinction between adenocarcinoma primary to the ovary and metastatic to the ovary can be difficult. In an effort to facilitate this distinction, we have evaluated the use of immunohistochemical techniques with antibodies to cytokeratins 7 and 20, along with antibodies to carcinoembryonic antigen. We studied 24 primary ovarian adenocarcinomas, 11 colonic adenocarcinomas metastatic to the ovary, and 10 primary adenocarcinomas of the colon. Four ovarian adenocarcinomas metastatic to the colon were also studied. All but one of the primary and metastatic colonic carcinomas were negative for cytokeratin 7, whereas all the primary and metastatic ovarian carcinomas were positive for cytokeratin 7. The tumors metastatic to the ovary were all positive for cytokeratin 20 and carcinoembryonic antigen. Among the primary ovarian carcinomas, none of six serous tumors, three of seven endometrioid tumors, and three of 11 mucinous tumors were positive for cytokeratin 20. Ten of the primary ovarian tumors were negative for carcinoembryonic antigen using both monoclonal and polyclonal antibodies. One of the ovarian tumors was negative for carcinoembryonic antigen with the monoclonal antibody but positive using the polyclonal antibody. Cytokeratin 7 is the most helpful marker in the distinction between primary ovarian carcinoma and colonic carcinoma metastatic to the ovary.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Ovarian Neoplasms

Characteristics of a panel of seven human ovarian tumour cell lines are presented. Positive staining with HMFG2 and ultrastructural identification of desmosomes confirmed the epithelial nature of the cell lines. The lines showed wide variations in ploidy, doubling times and clonogenicity in soft agar. Both vimentin and keratin were equally expressed in five lines, one line showed strong preferential expression of keratin and one line showed preferential expression of vimentin. Karyotypic changes associated with ovarian cancer were identified in all the lines. Four of the seven cell lines showed loss of chromosome material distal to 11p13-15. These cell lines offer considerable potential for research into the biology and genetics of ovarian cancer.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; Clone Cells; Cytogenetics; Desmosomes; Endoplasmic Reticulum, Rough; Female; Humans; Immunohistochemistry; Karyotyping; Keratins; Middle Aged; Mucin-1; Ovarian Neoplasms; Tumor Cells, Cultured; Vimentin

Walthard cell nests, the Brenner tumor (benign, proliferating, low malignant potential, and malignant), and primary ovarian transitional cell carcinoma are considered to be primary female genital tract proliferations of transitional-type (urothelial) epithelium on conventional light microscopic grounds. In order to further investigate the similarities (or dissimilarities) of proliferations of female genital tract transitional epithelium and urothelium, we compared transitional cell proliferations (TCPs) of the female genital tract (n = 25) and urinary bladder (n = 15) using antibodies to carcinoembryonic antigen (CEA; clone 0062), carbohydrate determinant 19-9 (CA19-9; clone 1116-NS-19-9), cytokeratin 7 (CK-7; clone OV-TL 12/30), and cytokeratin 20 (CK-20; clone Ks 20.8), four monoclonal antibodies that have been shown to stain transitional cell urothelial proliferations. Both groups of tumors exhibited significant staining for CEA, CA19-9, and CK-7, and the difference in numbers of cases staining was not significant. CA19-9 was present in 15 of 25 female genital tract TCPs as compared with 12 of 15 bladder TCPs; CEA was present in 17 of 25 female genital tract TCPs and nine of 15 comparable bladder TCPs. CK-7 was present in all cases studied with the exception of one Walthard cell nest and a malignant Brenner tumor that was not immunoreactive with the other antibodies tested. In contrast, 13 of 15 bladder TCPs were CK-20 positive, whereas only one of 25 female genital tract TCPs was positive (< 5% of cells). Walthard cell nests and benign Brenner tumors were more likely to be CA19-9 positive than were Brenner tumors of low malignant potential, malignant Brenner tumors, and primary transitional cell carcinoma of the ovary. We conclude that despite their apparent morphologic and immunologic similarity to TCPs of the urinary bladder (particularly at the histologically low-grade end of the transitional cells spectrum), Walthard cell nests and ovarian Brenner tumors constitute an immunophenotypically distinct form of TCP.

Topics: Antibodies, Monoclonal; Brenner Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Precancerous Conditions; Urinary Bladder Neoplasms

An ovarian gynandroblastoma in a 15-year-old girl is described. The predominant component was juvenile granulosa cell tumour. Areas of adult granulosa cell tumour and Sertoli cell elements were also present. Stromal theca and luteinised cells were identified. An additional histological finding was the presence of heterologous intestinal type glands. There was positive immunohistochemical staining of juvenile and adult granulosa cell areas with inhibin and MIC2 antibodies. Electronmicroscopy showed a close ultrastructural resemblance between tumour cells in granulosa and Sertoli cell areas, in spite of differences in architectural pattern, suggesting that both morphological components may derive from a single cell of origin. The tumour demonstrates a unique combination of elements which has not previously been described.

Topics: Adolescent; Female; Granulosa Cell Tumor; Humans; Immunohistochemistry; Intestinal Mucosa; Keratins; Male; Microscopy, Electron; Neoplasms, Gonadal Tissue; Ovarian Neoplasms; Sertoli Cells

The differentiation of ovarian metastases from colonic carcinoma and primary ovarian carcinoma can be difficult. To assess the utility of cytokeratin 7 and cytokeratin 20 immunostains in this setting, we studied routinely processed, formalin-fixed tissue from 165 ovarian tumors, including 45 serous carcinomas, 40 mucinous carcinomas, 64 endometrioid carcinomas, and 16 metastatic colonic adenocarcinomas with an avidin-biotin immunohistochemical technique. A cytokeratin 7+/cytokeratin 20- immunophenotype was seen in 86% of the endometrioid carcinomas, 27% of the mucinous carcinomas, 40% of the serous carcinomas, and none of the metastatic colorectal carcinomas. Conversely, a cytokeratin 7-/cytokeratin 20+ immunophenotype was seen in 94% of the metastatic colonic tumors, 5% of the mucinous carcinomas, and none of the endometrioid or serous tumors. We concluded that cytokeratin immunostains can be helpful in distinguishing metastatic colonic adenocarcinoma from primary ovarian carcinomas, particularly endometrioid carcinomas. Rare ovarian mucinous carcinomas may show the same immunophenotype as metastatic colonic carcinomas.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Endometrioid; Colonic Neoplasms; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms

The occurrence of approximately 5% of common epithelial malignant tumors of the ovary can be traced to inheritance of risk. One prophylactic strategy to decrease the probability of development of disease in individuals within families where this mendelian-dominant pattern of occurrence is apparent is to remove the ovaries of individuals at risk for ovarian cancer. The procedure, when done for this purpose, is recommended soon after completion of childbearing.. Our goal was to compare the histologic features of the ovaries of women at increased risk for ovarian cancer to those at no known increased risk for the disease.. Ovaries removed for prophylaxis from 20 women considered to be at increased risk for developing ovarian cancer were examined histologically. During the course of this work, it seemed apparent that these ovaries contained numerous atypical features compared with the expected appearance of normal ovaries. Hence, we expanded the study to include a control group whose ovaries were removed for reasons unrelated to cancer. The study, therefore, was not blinded. The increased risk in the cancer-prone individuals was determined by family history, specifically the presence of at least one first-degree relative and one second-degree relative with ovarian and/or breast cancer and positive linkage or mutational analysis of BRCA1 in some. The difference in mean ages of patients in the control and high-risk groups was not statistically significant. The difference among both groups with respect to the number of atypical features as well as the intensity of those features was ascertained by computing probabilities using Fisher's exact test (two-sided) for rows x columns contingency tables.. Two unanticipated microscopic or near-microscopic malignant neoplasms and other benign and borderline tumors were discovered in the ovaries of the high-risk individuals. Of substantial interest was the finding that among the ovaries of high-risk women, 85% presented two or more and 75% presented three or more of the following histologic features: surface epithelial pseudostratification; surface papillomatosis; deep cortical invaginations of the surface epithelium, frequently with multiple papillary projections within small cystic spaces (microscopic papillary cystadenomas); epithelial inclusion cysts, frequently with epithelial hyperplasia and papillary formations; cortical stromal hyperplasia and hyperthecosis; increased follicular activity; corpus luteum hyperplasia; or hilar cell hyperplasia. Two or more or three or more such changes were observed in a lesser percentage (30% or 10%, respectively) of ovaries obtained from the control individuals, with a statistically significant difference (P = .001 or P = .00007, respectively), particularly considering that a detailed determination of a family history of cancer in the control group was not possible.. The frequency of these changes in the high-risk ovaries compared with control ovaries suggests a characteristic histologic preneoplastic phenotype defined by an increased frequency and intensity of the above-described histologic features in the high-risk ovaries. Limited access to numerous small (stage I) ovarian cancers or cancer-prone ovaries by any one pathologist may explain the failure to identify the phenotype in the past.. We suggest that the ovaries removed from ovarian cancer-prone individuals as a preventative measure should be thoroughly examined histologically to identify or rule out microscopic or near-microscopic invasive neoplasms.

Topics: Adult; Carcinoma; Case-Control Studies; Female; Genetic Linkage; Humans; Keratins; Middle Aged; Neoplasm Invasiveness; Ovarian Neoplasms; Ovariectomy; Ovary; Phenotype; Polymorphism, Single-Stranded Conformational; Precancerous Conditions; Receptors, Estrogen; Risk

Epithelial ovarian carcinomas originate in the ovarian surface epithelium (OSE). In culture, OSE undergoes epithelio-mesenchymal conversion, an event mimicking a wound response, while ovarian carcinomas retain complex epithelial characteristics. To define the onset of this increased epithelial autonomy in ovarian neoplastic progression, we examined mesenchymal conversion in OSE from 25 women with no family histories (NFH-OSE) and 13 women with family histories (FH-OSE) of breast/ovarian cancer (including 8 with mutated BRCA1 or 17q linkage) and in 8 ovarian cancer lines. After 3-6 passages in monolayer culture, most NFH-OSE exhibited reduced keratin expression and high collagen type III expression. In contrast, keratin remained high but collagen expression was lower in p. 3-6 FH-OSE. This difference was lost in SV40-transformed lines, which all resembled FH-OSE. Most carcinoma lines remained epithelial and did not undergo mesenchymal conversion. In 3-dimensional (3-D) sponge culture, NFH-OSE cells dispersed and secreted abundant extracellular matrix (ECM). FH-OSE remained epithelial and did not secrete ECM. ECM production was also reduced in SV40-transformed lines. Carcinoma lines in 3-D formed epithelial cysts, aggregates and papillae and lacked ECM. Sponge contraction (a mesenchymal characteristic) was greater in NFH-OSE than in FH-OSE both before and after SV40 transformation and was absent in the cancer lines. Our results suggest that increased autonomy of epithelial characteristics is an early indicator of ovarian neoplastic progression and that phenotypic changes indicative of such autonomy are found already in overtly normal OSE from women with histories of familial breast/ovarian cancer.

Topics: Biomarkers, Tumor; Cell Line, Transformed; Collagen; Epithelium; Family Health; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Ovarian Neoplasms; Ovary; Phenotype; Tumor Cells, Cultured

Fourteen endometrioid carcinomas of the ovary with a prominent component of spindle-shaped epithelial cells are reported. Eleven were initially misdiagnosed as sexcord stromal tumors, malignant mesodermal mixed tumors, tumors of probable wolffian origin, or metastatic carcinomas. All of the tumors, however, had one or more features establishing them as endometrioid carcinomas, including (a) glands typical of endometrioid adenocarcinoma, (b) foci of squamous differentiation, and (c) an adenofibromatous component. Six cases were examined immunohistochemically, and the epithelial nature of the spindle cells was supported by immunostaining for keratin and epithelial membrane antigen. The patients ranged in age from 42 to 89 years (mean, 61). Four cases were stage I, five stage II, and three stage III. Follow-up information was available in seven cases. Five patients were free of disease at 8, 11, 32, 56, and 103 months, and two patients were alive with disease at 10 and 20 months. The age of the patients, clinical presentation, tumor stage, and gross appearance were similar to those of typical endometrioid carcinomas. It is important that this tumor be distinguished from other ovarian neoplasms with a spindle-cell component because of differences in treatment and prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoma; Diagnosis, Differential; Diagnostic Errors; Endometrial Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Mucin-1; Ovarian Neoplasms

Previously, we found that transforming growth factor beta (TGF-beta) inhibits proliferation of normal human ovarian epithelial cells. In addition, although only 1 of 5 immortalized ovarian cancer cell lines was inhibited, TGF-beta inhibited proliferation of 19 of 20 primary epithelial ovarian cancers. In this study, we examined whether TGF-beta induces apoptosis in normal and malignant ovarian epithelial cells. Among 5 immortalized cell lines, only OVCA 420 is markedly growth inhibited by TGF-beta, and this was the only cell line in which TGF-beta elicited DNA fragmentation characteristic of apoptosis. Induction of apoptosis in OVCA 420 was time and concentration dependent and could be partially inhibited by concurrent treatment with an anti-TGF-beta mAb. Although apoptosis was not seen in normal ovarian epithelial cells (n = 7), [3H]thymidine incorporation was inhibited in all cases [mean = 61.2 +/- 7.2% (SD) of untreated control; P < 0.01]. Similarly, TGF-beta inhibited [3H]thymidine incorporation in all 10 primary ovarian cancers (mean = 40.4 +/- 7.1% of control; P < 0.01), but only 3 of 10 (30%) were found to undergo apoptosis when treated with TGF-beta. There was no relationship between p53 status of the ovarian cancers and the ability of TGF-beta to elicit apoptosis. In conclusion, TGF-beta inhibits proliferation but does not induce apoptosis in normal human ovarian epithelial cells. In contrast, some ovarian cancers that are growth inhibited by TGF-beta also undergo apoptosis. These data are consistent with the hypothesis that malignant cells are more susceptible to apoptosis than their normal nontransformed counterparts.

Topics: Antibodies; Apoptosis; Cell Division; Epithelial Cells; Epithelium; Female; Genes, p53; Humans; Immunoblotting; Keratins; Ovarian Neoplasms; Ovary; Reference Values; Transforming Growth Factor beta; Tumor Cells, Cultured

Two permanent human ovarian clear cell adenocarcinoma lines (OVISE and OVTOKO) were established from metastatic tumors of two patients who were treated with five to six courses of CAP chemotherapy. The two cell lines grow on monolayers and showed a variety in both size and shape: small or moderately sized cuboidal cells, columnar cells, spindle-shaped cells, and malignant tumor giant cells. The cell lines have been in culture for 4 to 6 years, the passage number varying from 160 to 220. The mean population-doubling time of the two cells was 60 to 70 hr. The OVISE cells shed tumor-associated antigens CA19-9, CA125, and TPA in the culture medium, whereas the OVTOKO cells did not secrete them at detectable levels. Immunohistochemical analysis showed that coexpression of cytokeratins and vimentin was preserved in the two cell lines, which is a feature of cultured epithelial origin. Cytokeratin polypeptides 7, 8, 18, and 19 were expressed in both cell lines. The EGF receptor was more intensely expressed in the OVTOKO cells than in the OVISE cells. The estrogen and progesterone receptors were negative in both cell lines. The two cell lines showed no chemosensitivity to anticancer drugs including cisplatin, doxorubicin, cyclophosphamide, and etoposide. Heterotransplantation of the two cell lines reflected the origin of cells. Intraperitoneal transplantation of the OVTOKO cells yielded peritoneal implantation and distant metastasis, whereas that of the OVISE cells showed no dissemination and metastasis. These new ovarian clear cell adenocarcinoma lines will provide a relevant experimental system for further investigations into the intrinsic alterations responsible for malignant progression and chemoresistance.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cell Division; Desmin; Drug Resistance; ErbB Receptors; Female; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Metastasis; Neoplasm Transplantation; Ovarian Neoplasms; Time Factors; Tumor Cells, Cultured; Vimentin

The most common carcinomas metastatic to the ovary that mimic ovarian primaries are colonic adenocarcinomas and endometrial carcinomas. Conventional histochemical staining procedures, even in combination with additional immunohistochemical assays, are of limited value in distinguishing between these metastases and primary ovarian carcinomas. In this study we investigated whether the application of monoclonal antibodies against keratins 7, 8, and 20 could help in differentiating between these categories. The reactivity patterns of 40 carcinomas metastatic to the ovary were compared with those of their primary carcinomas on the one hand and with various primary ovarian carcinomas and mesotheliomas on the other. Colon cancer metastatic to the ovary was keratin 7 negative and keratin 20 positive in 94% of the cases; in contrast, all primary ovarian carcinomas were keratin 7 positive and keratin 20 negative, with the exception of two cases of mucinous cystadenocarcinoma. Ovarian metastases of gastric cancer usually contained keratins 7 and 20. Metastases of endometrial cancer to the ovary and primary ovarian carcinomas usually showed similar keratin expression. We propose that keratin 7 and 20 antibodies may be of help to distinguish between primary ovarian carcinomas and carcinoma metastases in the ovary.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Mesothelioma; Ovarian Neoplasms

We reviewed 51 serous effusions (50 peritoneal/one pleural) from 38 patients with uterine (30 cases) and ovarian (eight cases) malignant mixed Müllerian tumors (MMMT). There were 16 patients (42%) with positive effusion cytology specimens; 13 cases (81%) were diagnosed as adenocarcinoma with three cases (19%) interpreted as having a sarcomatous component. Eight of 16 positive effusion specimens had cell block material available for immunoperoxidase (IP) study that included cytokeratin (AE1/3), vimentin, muscle specific actin (HHF) and S-100 protein to determine if unsuspected mesenchymal components were present in the cases originally diagnosed as carcinoma (six cases), or sarcomas (two cases). In the six cases originally interpreted as carcinoma, three were diagnosed as adenocarcinoma and three as poorly differentiated carcinoma. All three of the cases considered adenocarcinoma and two of those diagnosed as poorly differentiated carcinoma reacted only with AE1/3 and vimentin. The remaining case, considered a poorly differentiated carcinoma, stained only with vimentin. In the two cases having cell blocks interpreted as having a sarcomatous component, only vimentin was positive in one while AE1/3, vimentin, HHF, and S-100 were positive in the other. The case where all immunohistochemical stains were reactive contained both carcinomatous and sarcomatous components. In the three cases considered sarcomatous, the cytomorphologic features helpful in the recognition of a mesenchymal component included a dissociated smear pattern of pleomorphic round to oval cells and/or spindle cells. In retrospect, the IP stains did not alter any of the original diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ascitic Fluid; Female; Humans; Immunohistochemistry; Keratins; Mixed Tumor, Mullerian; Ovarian Neoplasms; Pleural Effusion, Malignant; Staining and Labeling; Uterine Neoplasms; Vimentin

We established an in vitro peritoneal dissemination model using six ovarian cancer cell lines and cultured mesothelial cells. Ovarian cancer cells were classified into two types, invasive or adhesive, on the basis of their interaction with the mesothelial cell monolayer. The ovarian cancer cell lines derived from mucinous cystadenocarcinoma, poorly differentiated adenocarcinoma and undifferentiated carcinoma, which belonged to the invasive type, began to invade beneath the mesothelial monolayer from several hours after seeding in vitro, expelling the mesothelial cells at the periphery and forming colonies directly on the dish surface. On the other hand, cancer cell lines of clear cell carcinoma, which belonged to the adhesive type, showed colony formation with adhesion on the mesothelial monolayer even 18 h after seeding. Invasive-type cell lines invaded into the mesothelial monolayer at various rates in vitro, and the degree of invasiveness showed good correlation with the degree of peritoneal dissemination in vivo after intraperitoneal injection of cancer cells into nude mice. Adhesive-type cells showed rather higher dissemination rates in vivo. Microscopic observation of in vivo peritoneal dissemination at one day after inoculation also revealed two patterns of peritoneal involvement similar to those in vitro. In the in vitro model, anti-integrin alpha 2- and beta 1-antibodies inhibited the infiltration of invasive-type cells into the mesothelial monolayer, but did not affect colony formation by adhesive-type cells on the monolayer, indicating that invasion by both cell types was mediated by different molecules. This in vitro model is thought to be useful for analysis of the molecular mechanisms of peritoneal dissemination.

Topics: Animals; Cell Adhesion; Cells, Cultured; Epithelial Cells; Epithelium; Factor VIII; Female; Humans; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; Omentum; Ovarian Neoplasms; Peritoneal Neoplasms; Tumor Cells, Cultured; Vimentin

Cytokeratin 7 (CK-7) is a simple epithelial keratin that may be used to investigate the site of origin of adenocarcinomas. In fact, CK-7 is present in ovarian epithelial neoplasms but is generally absent in colonic carcinomas. This pattern of CK-7 expression may aid in elucidating the genesis of mucinous tumors occurring simultaneously in the ovary and appendix, accompanied by psuedomyxoma peritonei. Five such cases were immunostained with anti-CK-7, and all showed a concordant staining pattern of the appendiceal, ovarian, and peritoneal lesions. Two cases showed a negative reaction for CK-7 and thus would appear to represent ovarian and peritoneal metastases from an appendiceal primary tumor. Three cases were CK-7 positive, and the nature of these mucinous lesions remains open to debate; they may either represent independent primary tumors or originate from the appendix. For comparison, five Stage I mucinous borderline tumors of the ovary and their normal appendices were also stained with anti-CK-7. These ovarian tumors were all CK-7 positive, whereas the appendices were negative. It is concluded that CK-7 is capable of distinguishing a group of tumors that can reliably be classified as primary appendiceal neoplasms metastatic to the ovaries and peritoneum.

Topics: Adult; Aged; Aged, 80 and over; Appendiceal Neoplasms; Cystadenocarcinoma, Mucinous; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Pseudomyxoma Peritonei

We measured serum cytokeratin fragment 21-1 (CYFRA 21-1) levels by a solid-phase immunoradiometric assay in 102 healthy Japanese women, and set the reference value at 1.9 ng/ml (mean +2 SD of the serum levels based on a linear distribution). Pretreatment serum CYFRA 21-1 levels were also analyzed in 235 women with benign (n = 94) or malignant (n = 141) gynecologic disease, and were compared with the serum levels of CA 125 and SCC. The respective positivity rates for CYFRA 21-1 and CA 125 were 64.0 and 77.2% in ovarian malignancy, while they were 4.2 and 30.8% in benign ovarian masses. CYFRA 21-1 had an accuracy of 61.3% in diagnosing ovarian malignancy, which was higher than that of CA 125 (53.4%). The positive predictive value of CYFRA 21-1 for ovarian malignancy reached 94.1%, which was significantly (p < 0.005) higher than that of CA 125 (68.8%). These findings indicate the potential usefulness of CYFRA 21-1 as a tumor marker for ovarian malignancy. In addition, the positivity rates fo CYFRA 21-1 in cervical cancer (51.2%) and endometrial cancer (52.2%) were also similar to the respective rates for SCC and CA 125, which suggests that CYFRA 21-1 seems to be a general tumor marker for gynecologic malignancy.

Topics: Adolescent; Adult; Biomarkers, Tumor; CA-125 Antigen; Cysts; Endometrial Neoplasms; Female; Genital Neoplasms, Female; Humans; Immunoradiometric Assay; Keratins; Middle Aged; Ovarian Diseases; Ovarian Neoplasms; Reference Values; Uterine Cervical Neoplasms; Uterine Diseases; Uterine Neoplasms

DNA is the primary target of cis-diamminedichloroplatinum (cisplatin), but the drug also interacts with the cellular cytoskeleton composed of microtubules and intermediate filaments. It was found that the cisplatin-resistant 2008/C13* cell line contained markedly lower levels (6-fold) of cytokeratin 18, when compared to the cisplatin-sensitive 2008 cell line. Northern blot analysis revealed a markedly decreased level of cytokeratin 18 mRNA in the resistant cell line. Southern blot analysis of the DNA extracted from the two cell lines and then digested with HpaII and its methylation-sensitive isoschizomer, MspI, revealed no detectable differences in the methylation status of the cytokeratin gene. Neither 5-azacytidine (5 microM) nor retinoic acid (1 microM) treatment enhanced the expression of cytokeratin 18 in the resistant cell line. However, transfection of full-length cytokeratin 18 cDNA into the cisplatin-resistant 2008/C13* cells resulted in clones with increased levels of cytokeratin 18, which was accompanied in the majority of clones by a marked increase in their sensitivity to cisplatin. These results demonstrate that modulating the expression of an intermediate filament protein results in sensitization of a drug-resistant human ovarian cell line to cisplatin.

Topics: Adenocarcinoma; Antineoplastic Agents; Azacitidine; Cisplatin; DNA Damage; Drug Resistance; Female; Humans; Keratins; Ovarian Neoplasms; Tumor Cells, Cultured

A rare case of carcinoma developed in struma ovary in 55 year-old woman. During surgical intervention, the carcinoma infiltration in ovary stroma was diagnosed. The metastases were not stated. In the immunohistochemical assay, thyroglobulin and cytokeratin in neoplastic cells were displayed. Clinical examination did not show any signs of hyperthyreosis.

Topics: Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Ovarian Neoplasms; Thyroglobulin

Two human ovarian (OV-MZ-10, OV-MZ-15) and two colon cancer cell lines (CO-MZ-5, CO-MZ-6) were newly established in permanent cell culture. These cell lines have been maintained in vitro for 5-6 years, the passage number varying from 25 to 228. They were established from ascites or solid tumours at the time of primary surgery. By clinical and histopathological judgement alone all four cell lines would have been interpreted as ovarian cancer cell lines. Morphological criteria or the expression of the tumour-associated antigens CA-125 and CEA allowed no differential diagnosis. Only the analysis of the expression of different cytokeratins and vimentin enabled us to verify the different origin of the cell lines. Ovarian cancer cell lines, in contrast to the colon cancer cell lines, are positive for the expression of cytokeratin (CK) 7 and for vimentin. CK 20 proved to be the marker with the best discrimination. CK 20 was found exclusively in the colon carcinoma cell lines, but not in the ovarian carcinoma cell lines. The evaluation of cytokeratin expression is a helpful diagnostic modality in differentiating between adenocarcinoma cell lines derived from ovarian and colon tumours.

Topics: Adult; Aged; Animals; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Cell Division; Cell Line; Colonic Neoplasms; Culture Techniques; Female; Humans; Keratins; Male; Mice; Mice, Nude; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Ovarian Neoplasms; Transplantation, Heterologous; Tumor Cells, Cultured

Epidermolytic palmoplantar keratosis (EPPK) cosegregates with breast and ovarian cancers in a large French pedigree, raising the possibility that a single genetic mutation might cause these conditions and offering a potential lead to the identification of a hereditary breast/ovarian cancer gene. We have performed linkage analysis and show that the EPPK locus lies on the long arm of chromosome 17 near the type I keratin gene cluster and the proposed breast cancer gene (BRCA1). The type I keratin 9 gene has been partially sequenced in four affected individuals. A single base mutation within the rod domain of the protein cosegregates with EPPK in all affected individuals tested. Although inheritance of this mutation is likely responsible for EPPK, it is unlikely to be the cause of the breast and ovarian cancer.

Topics: Adolescent; Adult; Amino Acid Sequence; Base Sequence; Breast Neoplasms; Chromosomes, Human, Pair 17; DNA Mutational Analysis; DNA Primers; Female; France; Genetic Linkage; Humans; Keratins; Keratoderma, Palmoplantar; Male; Middle Aged; Molecular Sequence Data; Ovarian Neoplasms; Pedigree; Point Mutation

In an attempt to assess and improve the histological classification of ovarian tumors the value of immunohistochemical techniques has been examined in 50 ovarian tumors. A panel of six immunohistochemical markers (two cytokeratins, EP4, EMA, CEA, and vimentin) seems to have no additional value in differential diagnosis and typing of ovarian tumors.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Brenner Tumor; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Cystadenocarcinoma, Mucinous; Cystadenocarcinoma, Serous; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Mucins; Ovarian Neoplasms; Vimentin

Three women, aged 19, 21, and 30 years, two with the Peutz-Jeghers syndrome (PJS), had unilateral ovarian tumors composed of Sertoli cells with abundant eosinophilic cytoplasm. Electron microscopical and immunohistochemical examinations in one case supported the diagnosis of a sex cord tumor. Two patients are well 3 and 20 months postoperatively; the third was well for 15 years when recurrent tumor involving multiple intraabdominal sites was discovered. The occurrence of two of these tumors in patients with PJS and the known increased frequency of sex cord tumors in patients with this syndrome indicate an association. Sertoli cell tumor should be included in the differential diagnosis of oxyphilic ovarian tumors, particularly if there is a tubular pattern.

Topics: Adult; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasms, Multiple Primary; Ovarian Neoplasms; Peutz-Jeghers Syndrome; Sertoli Cell Tumor; Sex Cord-Gonadal Stromal Tumors; Vimentin

To begin delineating the cellular and molecular events that are important in ovarian carcinogenesis, we have developed a simple and rapid method for the establishment of primary cultures derived from benign tumors, malignant tumors, and ascites of the ovary that are representative of the original clinical material from which they are derived. From 23 ovarian epithelial ascites collected, 13 were successfully established in culture and cells survived an average of 7 to 8 passages. From 65 solid epithelial ovarian tumors (benign and malignant) 36 were cultured for an average of 6 passages for cultures derived from benign tumors and 11 or 12 passages in the case of malignant tumors. Cells were scored as epithelial in nature by morphology and histochemical analysis using anti-cytokeratin antibodies. Cultures, especially those derived from solid tumors, sometimes displayed fibroblastic-like contamination which was quickly resolved. We include limited molecular analyses both to characterize the origin of the populations we have established as well as to demonstrate the usefulness of these cultures in molecular studies.

Topics: Ascites; Cell Division; Cells, Cultured; DNA; DNA, Neoplasm; Epithelial Cells; Epithelium; Female; Genes, p53; Humans; Immunohistochemistry; Keratins; Mutation; Ovarian Neoplasms; Ovary; Tumor Cells, Cultured

A total of 30 sex cord-stromal tumors including 9 adult type and 5 juvenile type granulosa cell tumors (GCTs), 4 Sertoli-Leydig cell tumors (SLTs), 1 gynandroblastoma, 5 thecomas, 2 fibromas and 3 sclerosing stromal tumors were immunohistochemically evaluated by means of cytokeratins of different molecular weight, vimentin and laminin with regard to the histogenesis of these tumors and to the embryogenesis of the sex cord and stroma of developing gonads. For comparison, 7 embryonic gonads, 9 fetal and 9 adult ovaries, 14 fetal and 5 postnatal testes, and 1 gonadoblastoma were also examined. The coelomic epithelium of all gonads were positive for both cytokeratins (CAM 5.2 and AE1) and vimentin. In fetal ovaries, the granulosa cells of primordial follicles express low molecular weight cytokeratins only and those cells of more maturing follicles did not express any cytokeratin or vimentin. In adult ovaries, the granulosa cells of primordial follicles coexpressed low molecular weight cytokeratins and vimentin, but those cells of more maturing follicles expressed vimentin only. In fetal testes before 20 weeks gestational age, the Sertoli and Leydig cells did not express any cytokeratins and vimentin. After that time, both cells expressed vimentin only throughout life. The rete ovarii and rete testis from fetal to adult life coexpressed both low molecular weight cytokeratins and vimentin. The rete ovarii in all ages and rete testis in prenatal and childhood ages were surrounded by the laminin-positive basement membrane, however, the rete testis in adult were not. In neoplasia, the GCTs, thecomas, fibromas, and sclerosing stromal tumors expressed vimentin only.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Basement Membrane; Child, Preschool; Female; Fetus; Fibroma; Gonadoblastoma; Humans; Immunohistochemistry; Infant; Keratins; Laminin; Male; Molecular Weight; Neoplasms, Gonadal Tissue; Ovarian Neoplasms; Ovary; Sertoli-Leydig Cell Tumor; Sex Cord-Gonadal Stromal Tumors; Testis; Thecoma; Vimentin

Tumor stroma contains much fibrin and monoclonal antifibrin antibody targeting is possible in tumors. In this study, nude mouse human ovarian carcinoma xenograft specimens were investigated after treatment with 90Y-labeled monoclonal antifibrin antibody Fab fragment or with 90Y-labeled OC125-monoclonal antibody F(ab')2 fragments. The mice received the radioimmunotherapy activity either intratumorally, intraperitoneally, or intravenously. Beta-camera imaging (BCI) is a novel device for studying activity distribution in tissue specimens and, together with immunohistochemistry (IHC) with OC125, antifibrin, anticarcinoembryonic antigen, anti-cytokeratin, and anti-placental alkaline phosphatase antibodies, was used for correlation of activity distribution of tissue specimens. These results were in concordance: Antigen distribution measured with IHC and radioactivity distribution were similar with the same antibodies, antifibrin, and OC125: However, these antigens demonstrated rather different distribution. Tissue studies revealed that activity was concentrated also in the necrotic tumor tissue, indicating that cell death was also caused by radiation. Differences in the tumor cell morphology were observed using different routes of administration. With BCI, it is possible to quantitate activities in frozen sections (microdosimetry), and these results were in concordance with absolute activities as measured by tissue sampling and well-counting. Three-dimensional reconstruction of tissue slices combined with radioactivity distribution measured with BCI allows estimation of total absorbed radiation dose in tumor after an appropriate dose planning.

Topics: Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Disease Models, Animal; Female; Fibrin; Immunohistochemistry; Keratins; Mice; Mice, Nude; Ovarian Neoplasms; Proteins; Radioimmunotherapy; Radionuclide Imaging; Statistics as Topic; Yttrium Radioisotopes

Mucinous adenocarcinomas of the ovary were studied immunohistochemically for cytokeratins 7 and 18, either to determine whether the ovarian tumor was primary or a metastasis or to establish the histogenetic origin of the tumor. Primary ovarian tumors were strongly positive for both cytokeratins, while ovarian metastases from colonic cancers were negative for cytokeratin 7, as were the colonic cancers. Three of four ovarian tumors complicated by pseudomyxoma peritonei were negative for cytokeratin 7, indicating appendiceal origin. Two of seven mucinous tumors associated with dermoid cysts were negative for cytokeratin 7, suggesting gastrointestinal origin.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Colonic Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Ovarian Neoplasms; Pseudomyxoma Peritonei

Ovarian serous lesions with severe cytological and architectural atypia without obvious destructive stromal invasion may be diagnosed as serous borderline malignant tumor or as serous cystadenocarcinoma, depending on the criteria that individual pathologists use. The recent introduction of the diagnosis "serous borderline tumors with stromal microinvasion" seems an important improvement for the accuracy of the diagnosis of serous ovarian tumors. The aim of this study was to determine if immunohistochemical epithelial markers could help to detect stromal microinvasion in serous ovarian tumors and to compare these findings with the occurrence of "eosinophilic metaplastic" cells. Therefore, we studied the presence of eosinophilic metaplastic cells. Three immunohistochemical epithelial markers were applied in a group of 42 borderline and invasive serous tumors. The histopathologic diagnosis of the tumors was established by a reference center for gynecologic pathology in the Netherlands. We found that "eosinophilic metaplastic" cells were a constant feature in the serous borderline tumor lesions both with and without microinvasion. The presence of these cells should therefore not be considered as pathognomonic for microinvasion. The three investigated antibodies against epithelial epitopes helped to detect microinvasion, with the monoclonal antikeratin (CAM5.2) the best of these antibodies. Serous tumors diagnosed as carcinoma with dubious invasion showed no evidence of microinvasion in 83% of cases. In 13% of serous borderline malignant tumors, microinvasion was detected by the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Cystadenocarcinoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasm Invasiveness; Ovarian Neoplasms; Retrospective Studies; Serous Membrane

The marker profile of 18 samples of normal human ovarian tissues and 138 samples of their derived tumors was established using 51 monoclonal antibodies directed against intermediate filaments, ovarian carcinoma-specific antigens, general tumor-associated antigens and MHC-I/II antigens. Our data show that vimentin and keratins 7, 8, 18, and 19 were found in both epithelial and some nonepithelial ovarian tumors. Several tumor samples contained additional keratins 4, 10, 13, and 14, as well as desmin. BW 495/36 and to a lesser extent HMFG-2 were usually found in all ovarian tumors that contained simple epithelial keratins, except the absence of HMFG-2 in gonadal tumors as well as in dysgerminomas. In contrast to the keratin antibodies, these two panepithelial antibodies were negative in normal mesothelial cells and granulosa cells of the ovarian follicles. In general, the marker TAG-72 appeared useful for its discrimination between positively stained mucinous adenomas, the ovarian carcinomas as well as germ cell tumors, and the negatively stained gonadal tumors, serous adenomas, and cystomas. OV632 appeared useful in the distinction between negatively stained serous adenomas and positively stained serous carcinomas. In contrast, the monoclonal antibodies OC 125, OV-TL 3, OV-TL 16, and MOv 18 can be considered as pan-ovarian carcinoma markers, however without the discriminative capability as seen for OV632. These ovarian carcinoma-associated antigens were hardly found expressed in gonadal and germ cell tumors, except in the group of endodermal sinus tumors. HLA-I was found to be expressed in almost all nucleated cells, although loss of HLA-I expression was seen in areas of tumor cells. HLA-DR was negative in normal ovarian tissue, but heterogeneous expression was noticed in most of the epithelial tumors.

Topics: Adenoma; Antibodies, Monoclonal; Antigens, Differentiation; Biomarkers, Tumor; Cell Transformation, Neoplastic; Diagnosis, Differential; Epithelium; Female; Humans; Keratins; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Ovary

In an attempt to clarify the histogenesis of carcinosarcoma (malignant mixed müllerian tumor) of the female genital tract, 20 uterine and eight ovarian tumors were studied by light microscopy, transmission electron microscopy, and immunohistochemistry. Cytokeratins (MAK-6 and AE1:AE3) and epithelial membrane antigen were detected in the epithelial component of all tumors and in the stromal component of 15 cases (55%). Vimentin was detected in the stromal component of all cases and was focally positive in the epithelial component of 18 cases (69%). Tumors showing rhabdomyosarcomatous or chondrosarcomatous differentiation were positive for myoglobin and S-100 protein, respectively. At the ultrastructural level epithelial cells were observed in tight clusters (usually surrounded by a basal lamina), in loose aggregates, and singly (sometimes spindle shaped), and were surrounded by cells displaying variable differentiation. The closest examples of "hybrid" epithelial/stromal cells were those with a prominent rough endoplasmic reticulum, cytoplasmic projections, poorly formed intercellular junctions, and an incomplete basal lamina. The observations support the view that carcinosarcomas of the female genital tract could represent examples of biphasic (metaplastic) carcinomas.

Topics: Aged; Antigens, Neoplasm; Carcinosarcoma; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Myoglobin; Ovarian Neoplasms; S100 Proteins; Uterine Neoplasms; Vimentin

A case of granulosa cell tumor of the ovary associated with hepatocytic differentiation is reported in a 45-year-old patient with a torsioned ovarian tumor. Serum alpha-fetoprotein (AFP) levels were normal 6 days postoperatively. Histopathologically, the granulosa cell tumor was typically trabecular. Its cells had nuclear grooves and were positive only for vimentin. Scattered diffusely throughout the tumor were small groups of regular polygonal cells, the cytoplasm of which secreted bile and was strongly positive for keratin, carcinoembryonic antigen (CEA), alpha-1-antitrypsin (A1AT), and ferritin and moderately positive for fibrinogen and ceruloplasmin. These results unequivocally identified them as hepatic cells. The AFP negativity of the hepatic cells was interpreted as a sign of terminal hepatocytic differentiation. The scattered arrangement of the hepatocytes simulated stromal luteinization. As neither a primary liver tumor nor any associated germ cell tumor was found, the histogenesis of the hepatic cells was thought to be metaplastic.

Topics: alpha 1-Antitrypsin; alpha-Fetoproteins; Carcinoembryonic Antigen; Cell Differentiation; Cell Nucleus; Female; Ferritins; Granulosa Cell Tumor; Humans; Immunohistochemistry; Keratins; Liver; Liver Diseases; Luteal Cells; Metaplasia; Middle Aged; Ovarian Neoplasms; Ovary; Vimentin

Ovarian myxomas recently have been reported as new, distinct pathologic entities that show a myxoid, moderately cellular proliferation of spindle and stellate cells interspersed with areas of fibrosis, hemorrhage, and delicate vascular spaces. These histologic features are frequently seen in the thecoma-fibroma group of ovarian stromal tumors. For this reason, we propose that ovarian myxomas are part of the spectrum of differentiation in thecomas-fibromas of the ovary. To provide histologic and immunohistochemical evidence for this proposal, four ovarian myxomas were compared with 48 primary ovarian stromal tumors in the thecoma-fibroma group from 46 patients. The thecoma-fibroma group of stromal tumors included 23 thecomas, 23 fibromas, and two sclerosing stromal tumors. We found significant (> 25% of histologic appearance) myxoid change in six thecomas and one sclerosing stromal tumor. This myxoid change resembled the histologic appearance of an ovarian myxoma. Immunohistochemical studies on paraffin-embedded material showed vimentin immunostaining in all tumors. Smooth-muscle actin was present in all of the myxomas, in two of the two sclerosing stromal tumors, and in 20 (90%) of the 23 thecomas, but it was present in only 11 (48%) of the 23 fibromas. Desmin staining was not present in any of the four ovarian myxomas or in the two sclerosing stromal tumors, and only three (13%) of the 23 thecomas showed focal staining for desmin. Nine (39%) of the 23 fibromas expressed desmin. S100 protein was expressed in one fibroma and one thecoma, weakly. None of the ovarian myxomas or the thecoma-fibroma group of stromal tumors expressed cytokeratins as detected by three different monoclonal antibody cocktails, ie, cytokeratin AE1/AE3, cytokeratin CAM 5.2, or cytokeratin MAK-6. The ovarian thecoma-fibroma group of stromal tumors form a histologic spectrum of lesions in which clear-cut distinguishing points between various entities are difficult to define. The myxoid change, present in the thecoma-fibroma group of tumors, was indistinguishable histologically and immunohistochemically from ovarian myxoma. For this reason, we propose that ovarian myxomas may be at one end of the spectrum of differentiation in the thecoma-fibroma group of tumors, in which no remaining stromal tumor is detectable.

Topics: Actins; Adult; Aged; Antibodies, Monoclonal; Desmin; Female; Fibroma; Humans; Immunohistochemistry; Keratins; Middle Aged; Myxoma; Ovarian Neoplasms; Thecoma; Vimentin

We developed a new and automated assay for the detection of lung cancer associated cytokeratin 19 fragments in patients' sera/plasma. This new tumour marker assay CYFRA 21-1 was evaluated in technical and clinical studies using the multibatch analysers ES 300 and ES 600 from Boehringer Mannheim GmbH. The analytical performance was shown to be excellent. The clinical data from 2,037 patients demonstrate that for non-small-cell lung carcinoma CYFRA 21-1 has a higher diagnostic sensitivity compared to the established markers. Mainly for squamous cell carcinoma CYFRA 21-1 was superior (60%) to CEA (18%) or SCC (31%).

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Lung Neoplasms; Male; Ovarian Neoplasms; Peptide Fragments; Sensitivity and Specificity; Stomach Neoplasms

The clinicopathological and immunohistochemical features of 7 cases of benign and malignant Brenner tumor of the ovary, including 5 benign and 2 malignant tumors are described. Microscopically, all of the benign cases were composed of both epithelial nest and fibrous stroma. Two cases of the malignant Brenner tumor showed that the histologic features resembled the structure of non-keratinized squamous carcinoma or transitional cell carcinoma. Immunohistochemistry showed that tumor cells of the epithelial nest were keratin and EMA positive in 7 cases; CEA-positive in 5 cases; and negative in 2 cases of benign Brenner tumor. The results indicated that Brenner tumor is an epithelial neoplasm in nature. The diagnostic criteria and histogenetic origin are discussed.

Topics: Aged; Brenner Tumor; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Ovarian Neoplasms

Interrelationships between neoplastic progression and the expression of intermediate filaments were examined in primary cultures, immortal lines, and Kirsten murine sarcoma virus (KiMSV) transformed lines of rat ovarian surface epithelial (ROSE) cells. Immunofluorescence microscopy revealed abundant keratin filaments in all cells of primary cultures. In immortal, nontumorigenic lines, keratin filaments were detected in fewer cells, in smaller numbers, and in microscopically altered forms. The percentage of keratin-positive cells ranged from 4 to 54%. Its expression was inversely proportional to cell density. Keratin expression was similar in the two immortal lines, although one had retained a monolayered epithelial growth pattern resembling primary cultures, while in the other the growth pattern of the cells was more atypical. The two KiMSV-transformed lines were previously shown to produce tumors in vivo that resemble human ovarian endometrioid stromal sarcomas. In spite of this histologic appearance, the proportion of keratin-positive cells in these cells was increased over the immortal lines. Keratin expression was unrelated to cell density, and keratin in most virally transformed cells was limited to few, fine filaments. In thymidine-labelled immortal and virus-transformed cultures stained for keratin, no correlation was found between keratin expression and proliferative activity. The keratin profiles of primary and immortal cultures were identical on Western blots, with subtypes ranging from 52 to 66 kDa. The two virally transformed lines lacked some of the subtypes. Vimentin networks were faint or absent in primary cultures. In the immortal and the virus-transformed lines, neoplastic progression was associated with increasing vimentin expression but with no changes in filament morphology and distribution. The results show that the abnormalities in intermediate filament expression that accompany immortalization do not preclude the retention of a normal epithelial morphology and growth pattern in this cell type. Furthermore, the number of intermediate filaments and their intracellular distribution appear to be altered at an earlier stage in neoplastic progression than those mechanisms that select for specific keratin subtypes, or those that respond to regulation by cell density. Finally, the presence of keratin in the KiMSV-transformed lines examined in this study supports the hypothesis that human ovarian stromal sarcomas can arise in the OSE.

Topics: Animals; Cell Division; Cell Transformation, Neoplastic; Cells, Cultured; Epithelium; Female; Immunohistochemistry; Intermediate Filaments; Keratins; Ovarian Neoplasms; Ovary; Rats; Vimentin

Primary tumors of the peritoneum are rare. Histological differentiation between papillary mesotheliomas, primary ovarian tumors, borderline tumors of the ovary with peritoneal deposits and primary peritoneal carcinoma may be difficult. The expression of vimentin, keratin, pankeratin, CEA, CA125, CA19-9, S100, B72.3 and BerEP4 was therefore investigated in twelve women with primary malignant peritoneal tumors, twelve women with pleural mesothelioma, eight women with serous ovarian carcinoma and four men with peritoneal mesothelioma. The marker pattern we used was no help in differentiating between metastatic ovarian carcinoma and primary peritoneal carcinomatosis. A combination of the markers S100, B72.3 and BerEP4 helped the distinction between mesotheliomas and the other malignancies. If two or all three markers are detectable, primary peritoneal carcinomatosis or metastatic ovarian carcinoma is the possible diagnosis. If none of the three markers are found, a diagnosis of mesothelioma is highly probable.

Topics: Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Ovarian Neoplasms; Peritoneal Neoplasms

One of the problems in histopathology of ovarian tumors is differential diagnosis between the poorly differentiated carcinomas and granulosa cell tumors of the sarcomatoid type. Hence we evaluated the expression of various cytokeratins (CK 1-19; CK 10, 13, 14, 15, 19; CK 8, 18, 19; CK HMW 1, 5, 10, 11; CK 8; CK 1-19 Stähli; CK AE1/AE3) immunohistochemically in 53 ovarian malignancies (11 of them poorly differentiated carcinomas and 12 granulosa cell tumors). CK HMW was not detected in granulosa cell tumors, and in only half of the carcinomas. AE1/AE3 was expressed by more than 90% of ovarian carcinomas but by one granulosa cell tumor only. The other keratins we investigated showed higher expression rates in granulosa cell tumors and/or lower expression rates in ovarian carcinomas. We think that cytokeratin immunohistochemistry is of value in differentiating between granulosa cell tumors and ovarian carcinomas.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Granulosa Cell Tumor; Humans; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms; Ovary

Eleven primary ovarian tumors that resembled small cell carcinoma of the lung are reported. They occurred in women 28-85 (mean 59) years of age, most of whom presented with abdominal swelling. Six of the tumors were unilateral and five bilateral; seven had spread beyond the ovary. The tumors ranged from 4.5 to 26 (mean 13.5) cm in greatest dimension and were mostly solid, with a variable minor cystic component. Microscopic examination showed small to medium-sized round to spindle-shaped cells with scanty cytoplasm, hyperchromatic nuclei, and inconspicuous nucleoli growing in sheets, closely packed nests, and occasionally islands and trabeculae. A component of endometrioid carcinoma was present in four tumors, another tumor showed squamous differentiation, another contained a cyst lined by atypical mucinous cells, and two others were associated with a Brenner tumor. Argyrophil granules were present focally in two of six tumors appropriately stained. Immunohistochemical staining was performed in nine cases: in six there was staining of the small cell component for keratin, in five for epithelial membrane antigen, in seven for neuron-specific enolase, in two for chromogranin, and in one for Leu-7. Vimentin staining was not observed. Flow cytometry was performed on eight tumors: five were aneuploid and three diploid. Five of seven patients with long-term follow-up died of, or with, disease at 1-13 (mean 8) months, one died after an unknown interval, and one was alive at 7.5 years. Two other patients had recurrent or residual disease at 6 and 8 months.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Small Cell; Chromogranins; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Ovarian Neoplasms; Phosphopyruvate Hydratase; Recurrence

Adult granulosa cell tumors (AGCTs) are classified as sex cord-stromal tumors of the ovary. However, they may be confused with other primary ovarian neoplasms. Intermediate filaments, specifically vimentin and cytokeratins, have been identified in AGCTs by immunohistochemistry performed on frozen and formalin-fixed, paraffin-embedded tissue and two-dimensional electrophoresis. Recently, however, immunohistochemical demonstration of cytokeratin has been used as supporting evidence of epithelial rather than sex cord-stromal differentiation in ovarian neoplasia. To investigate further intermediate filamentous proteins in AGCTs, 25 such tumors were studied by immunohistochemistry in formalin-fixed, paraffin-embedded sections. Cytoplasmic staining was observed, frequently in a distinct punctate, paranuclear pattern, in 14 of 25, 14 of 25, and seven of 17 tumors using monoclonal antibodies AE1/AE3, CAM 5.2, and 35BH11, respectively, which share the ability to detect low molecular weight cytokeratins. Staining for cytokeratin was not seen in any of the 17 tumors studied using the antibody 34BE12. Twenty-three of 25 tumors showed strong positivity for vimentin, characteristically seen as globoid paranuclear staining. Nine of 25 tumors contained desmin, which was restricted to the intermixed spindle cell, cortical type stromal component of the tumors. These patterns of immunoreactivity for intermediate filaments, particularly cytokeratins, are different than in common epithelial tumors of the ovary and may be useful in the differential diagnosis of ovarian neoplasia. Moreover, the immunohistochemical detection of cytokeratins should not be used as a criterion for excluding AGCT from the differential diagnosis of an ovarian neoplasm.

Topics: Electrophoresis, Gel, Two-Dimensional; Female; Granulosa Cell Tumor; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Ovarian Neoplasms; Vimentin

Primary tumours from 40 patients with epithelial ovarian cancer, treated at St Thomas's Hospital over a 10-year period, were studied for the immunocytochemical expression of the following tumour markers in formalin-fixed paraffin embedded material: carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CAM 5.2), and DD9. An indirect immunoperoxidase staining technique was used. All of the tumours were positive for EMA and CAM 5.2, and 30% of them were positive for both CEA and DD9. The absence of CEA and DD9 may be of value in differentiating between metastatic abdominal adenocarcinomas of ovarian origin and those of gastrointestinal origin, but no indication of prognosis was obtained using these epithelial markers. The strong and widespread staining of all the tumours for EMA suggests that this may be a useful marker for detecting metastatic or recurrent disease by immunoscintigraphy.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Cystadenocarcinoma; Endometriosis; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Ovarian Neoplasms

Three cases (two ovarian and one retroperitoneal) of mucinous tumors with solid nodules are reported. The predominant picture in the three cases was that of a mucinous cystic tumor, but small nodules of solid anaplastic carcinoma were found in all three cases. In addition, one case showed microscopic foci of microcyst rupture with histiocytic response reminiscent of sarcoma-like mural nodules, one case showed several sarcoma-like nodules, and one case showed apparent transition from anaplastic carcinoma to spindle cell sarcoma. Histologic and immunohistochemical characteristics of the lesions are given, as differentiation of these nodules is important.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; Cystadenocarcinoma; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Ovarian Neoplasms; Retroperitoneal Neoplasms; Sarcoma; Staining and Labeling; Vimentin

We examined the histologic, immunohistochemical, and clinical features of a series of 23 endometrial, five cervical, and one ovarian carcinosarcomas (malignant mixed müllerian [mesodermal] tumors) and nine associated distant peritoneal metastases. The primary tumors all showed epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) of the carcinomatous component, while sarcomatous areas showed epithelial differentiation in all but one case. The metastases showed uniform staining for cytokeratin (eight of eight cases) and epithelial membrane antigen (eight of eight cases), including the spindle cell component that was present in four of nine cases. Desmin significantly changed the interpretation of rhabdomyosarcoma differentiation by refuting putative rhabdomyoblasts in two cases and identifying rhabdomyoblasts in two other cases where they were unrecognized on hematoxylineosin staining. S100 protein was positive in all five cases with chondrosarcoma differentiation. Muscle-specific actin and vimentin were positive in the sarcomatous component of all cases and in the carcinomatous component of seven and 10 cases, respectively. After immunostaining, heterologous elements were present in 18 of 29 cases (11 cases of rhabdomyosarcoma, three cases of chondrosarcoma, three cases of mixed rhabdomyosarcoma and chondrosarcoma, and one case of liposarcoma). Only six of 27 patients with follow-up were disease free for 12 months or longer (associated with stage I or II disease, smaller size, no lymphatic invasion in the resection specimen, and no invasion of the outer two thirds of myometrium). Presence and type of heterologous elements, grade of sarcomatous or carcinomatous components, histologic type of carcinomatous component, gross appearance, presence of necrosis, or use of chemotherapy or radiotherapy did not affect outcome. Carcinosarcomas are clinically aggressive distinctive mixed epithelial-stromal neoplasms with histologic and immunohistochemical features that overlap with metaplastic carcinoma in many cases.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinosarcoma; Desmin; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasm Metastasis; Ovarian Neoplasms; S100 Proteins; Uterine Neoplasms

A higher prevalence of positive lymph node metastases can be found with immunohistological methods in comparison with conventional technique. We examined the lymph nodes from 20 patients with gynecological malignant tumors. We found in 304 lymph nodes with conventional technique 3.3% metastases. With immunohistological methods we showed in 9.9% of the lymph nodes metastases.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Female; Fluorescent Antibody Technique; Genital Neoplasms, Female; Humans; Keratins; Lymph Nodes; Mesonephroma; Neoplasm Staging; Ovarian Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms

The ovarian surface epithelium (OSE) is known to contribute to postovulatory repair of the ovarian cortex by proliferation and migration over the site of follicular rupture, and by deposition of a basement membrane. We examined the production of other extracellular matrix components in culture by OSE cells of the rat (ROSE), using immunofluorescence microscopy, electron microscopy, and proline incorporation. We compared recently explanted cells in low passage, the immortal line ROSE 239, whose growth pattern resembles low passage cultures, and the immortal line ROSE 199, which forms ridges and papillae. The epithelial nature of all three cell types was confirmed by the presence of keratin and laminin. All three cell types secreted collagen types I and III and at least one (ROSE 199) produced highly polymerized banded fibrils, which are characteristic for stromal or interstitial extracellular matrix. Simultaneous production of collagen types I and III, keratin, and laminin by cloned subpopulations ruled out an origin of the lines in mixed epithelial/fibroblast populations. The results demonstrate that OSE has the capacity to synthesize major components of connective tissue stroma. They suggest that this epithelium, in addition to its postulated proteolytic role, may also express synthetic activity in the remodelling of the ovarian cortical stroma. A capacity of OSE cells to produce stromal components autonomously might be an important factor in the formation of ovarian surface papillae and in neoplastic progression of OSE-derived ovarian carcinomas.

Topics: Animals; Cells, Cultured; Collagen; Connective Tissue; Epithelium; Extracellular Matrix; Female; Keratins; Ovarian Neoplasms; Ovary; Rats

We describe an ovarian mucinous cystadenocarcinoma with several sarcoma-like mural nodules (SLMN). The distinction between these lesions and foci of anaplastic carcinoma is important because of the poor prognosis of the latter. We have studied the potential value of immunohistochemistry in the differential diagnosis of these two lesions. In contrast to an anaplastic carcinoma, which was largely composed of keratin-positive cells, SLMN were negative or only focally positive. Therefore, in distinguishing SLMN from foci of anaplastic carcinoma, keratin strains may be added to other gross and microscopical differential features, such as size, demarcation, and presence or lack of obvious carcinomatous elements.

Topics: Adult; Carcinoembryonic Antigen; Cystadenocarcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Sarcoma

We report a case of extramammary Paget's disease in ovarian mature cystic teratoma. The patient was a 70-year-old Japanese woman who complained of lower abdominal pain. Examination showed elevation of carcinoembryonic antigen and CA 19-9. Ultrasonography and computer tomography revealed a cystic tumor of the left ovary. The gross appearance of the resected ovary was typical for mature cystic teratoma. Microscopic observation revealed a lesion of Paget's disease within the squamous epithelium. The tumor cells had intracytoplasmic mucin and positive immunoreactivity for carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin; but they were negative for S-100 protein and vimentin. On multiple and serial sections, underlying adenocarcinomas were not found either in the ovary or other primary sites. From these pathological findings, we concluded that the disease was an intraepithelial adenocarcinoma, possibly derived from multipotential cells in squamous epithelium of ovarian mature cystic teratoma. This is the first reported case, to our knowledge, of extramammary Paget's disease arising in mature cystic teratoma of the ovary.

Topics: Adenocarcinoma; Aged; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Dermoid Cyst; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; Paget Disease, Extramammary; S100 Proteins; Vimentin

A comparative immunocytochemical study was performed on endometriotic epithelial versus endometrial epithelial and normal mesothelial cells in order to obtain further evidence for either the endometrial implantation or mesothelial metaplasia theory. The three cell types could not be distinguished by keratin subtyping, using monoclonal antibodies (MAbs) to keratins 5, 7, 8, 14, 18, and 19. The epithelial markers HMFG-2 and BW 495/36, and a newly developed MAb NEND-3 (against endometrial cells) discriminated between generally negatively reacting mesothelial cells and positively reacting endometrial and endometriotic epithelial cells. The MAb NEND-3 appeared to be specific for endometrial (and endometriotic) epithelial cells since no reactivity with other epithelial cell types was found. Typing with MAbs against ovarian carcinoma related antigens (OV-TL 3, OV-TL 10 and OC 125) did not permit sufficient distinction. The marker profile of cultured endometrial, endometriotic and mesothelial cells confirmed the immunocytochemical findings on frozen sections. Although the data are consistent with the endometrial implantation theory, mesothelial metaplasia can not be excluded with regard to the histogenesis of endometriosis since metaplastic mesothelium may express different antigen markers.

Topics: Antibodies, Monoclonal; Biomarkers; Endometriosis; Endometrium; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms

A number of chemical agents have been found to influence the proliferation, morphology, enzymatic activity, and antigen expression of neoplastic cells toward a more differentiated phenotype. We studied the effects of differentiating agents retinoic acid, sodium butyrate, and dibutyryl cyclic AMP on the expression of the tumor-associated antigen CA 125 and several biochemical markers of differentiation in cultured OVCA 433 ovarian cancer cells. Treatment of OVCA 433 cells with these agents for 96 hr reduced cellular proliferation and altered cellular morphology. Quantitation of cell surface CA 125 using flow cytometry revealed that CA 125 expression was reduced by 35-50%. The amount of CA 125 antigen shed into the culture media was reduced to a similar degree. In addition, differentiation inducers markedly enhanced cellular alkaline phosphatase activity and induced the expression of a 65-67-kDa cytokeratin. These findings provide support for the induction of a more differentiated phenotype by these agents.

Topics: Adenocarcinoma; Alkaline Phosphatase; Antigens, Tumor-Associated, Carbohydrate; Bucladesine; Butyrates; Butyric Acid; Cell Differentiation; Dose-Response Relationship, Drug; Female; Humans; Keratins; Osmolar Concentration; Ovarian Neoplasms; Time Factors; Tretinoin; Tumor Cells, Cultured

The undifferentiated carcinoma cell line (HMG) was established from a nude mouse tumor which had been produced by transplantation of a intraperitoneal tumor of 27-year-old woman. The HMG cell line has the following biological properties. 1. The HMG cells are round to oval in shape and grow as floating cell aggregates like a rouleau or a cluster of grapes. 2. 100 passages have been carried out over a year, and the population doubling time is about 17 hrs. 3. In the original tumor, keratin and vimentin were expressed simultaneously, in HMG cells, however, only localization of vimentin was confirmed. 4. By chromosomal analysis, over 90% of the cells revealed 46, XX, with no karyological abnormalities, at passage 82. 5. When heterotransplanted into the subcutis of a nude mouse, HMG cells produced a undifferentiated carcinoma resembling the original tumor.

Topics: Adult; Animals; Biomarkers, Tumor; Carcinoma; Cell Division; Culture Media, Serum-Free; Female; Humans; Karyotyping; Keratins; Mice; Neoplasm Transplantation; Ovarian Neoplasms; Tumor Cells, Cultured; Vimentin

The patient described synchronous mucinous tumors of the cervix and ovary and concurrent annular tubules, but without the classical stigmata of Peutz-Jeghers syndrome. The cervical tumor was an invasive mucinous adenocarcinoma with mixed components of minimal deviation and less-well-differentiated endometrioid morphology. The ovarian tumor had the benign appearance of a mucinous adenoma but histologically revealed areas of invasive carcinoma. Immunohistochemical studies of the mucinous neoplasms of the cervix and ovary are discussed. Neither the staining properties of mucin, the pattern of immunostaining for carcinoembryonic antigen, nor any other common markers were helpful in distinguishing the mucinous neoplasms. Positive immunostaining for low-molecular-weight cytokeratin in the filament profile of sex cord tumors with annular tubules was of particular interest since it has not to our knowledge been previously described.

Topics: Adenocarcinoma, Mucinous; Adult; Antigens, Neoplasm; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Uterine Cervical Neoplasms

The paper describes an image analysis technique for automated selection of the epithelium-rich areas in standard paraffin tissue sections of ovarian and endometrial premalignancies and malignancies. Two staining procedures were evaluated, Feulgen (pararosanilin) and CAM 5.2, demonstrating the presence of cytokeratin 8 and 18; both were counterstained with naphthol yellow. The technique is based on the corresponding image processing method of automated estimation of the percentage of epithelium in interactively selected microscope fields. With the technique, one image is recorded with a filter to demonstrate where epithelium and stroma lie. This filter is chosen according to the type of staining: it is yellow (lambda = 552 nm) for Feulgen and blue (lambda = 470 nm) for anticytokeratin CAM 5.2. When stroma cannot be distinguished from lumina with the green filter or from epithelium with the blue filter, a second image is recorded from the same microscope field, with a blue filter (lambda = 420 nm) for Feulgen and a yellow filter (lambda = 576 nm) for anticytokeratin CAM 5.2. Discrimination between epithelium and stroma is based on the image contrast range and the packing of nuclei in the yellow image and on the automated classification of the gray value histogram peaks in the blue image. For Feulgen stain the method was evaluated on 30 ovarian tumors of the common epithelial types (8 borderline tumors and 22 carcinomas with various degrees of differentiation) and 30 endometrial carcinomas of different grades.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Endometrial Neoplasms; Epithelium; Female; Histocytological Preparation Techniques; Humans; Image Processing, Computer-Assisted; Keratins; Naphthalenesulfonates; Ovarian Neoplasms; Paraffin Embedding; Periodic Acid-Schiff Reaction; Receptors, Leukocyte-Adhesion

Formalin is hazardous for the environment and for the laboratory personnel and deleterious to cytoskeleton proteins. The pathology and anatomy laboratory can be formalin-free when Kryofix is used as a substitute fixative. In four years experience with Kryofix, we learned that immunostaining on paraffin sections is reproducible and of excellent quality. The current study concerns the comparison of interfilament staining on paraffin sections made from formalin or from Kryofix-treated tumors. For both keratin and vimentin there were false-negative findings in the formalin-fixed tumors. Of these two, vimentin was het most susceptible to formalin fixation. Three of the ten adenocarcinomas were positive for both keratin and vimentin, indicating that this double staining pattern is not uncommon. Postfixation of Kryofix-treated tissue with formalin results in false-negative immunostaining.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Ethanol; False Negative Reactions; Female; Fixatives; Formaldehyde; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Ovarian Neoplasms; Paraffin; Polyethylene Glycols; Vimentin

Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. In this study of 22 cases of SSC, it was found that the main clinical manifestations of SSC were abdominal pain and enlargement. In most cases, SSC evenly involved the entire mesothelial surface but rarely was predominant in or even limited to the pelvis. It frequently invaded the submesothelium, but deep invasion into abdominal and pelvic organs or local metastasis was rare, and distant metastasis was not seen at presentation. Microscopically, SSC was a high-grade tumor frequently showing high mitotic rate, psammomas bodies, and necrosis. The tumor was usually contiguous with hyperplastic mesothelium on either ovarian surface or other locations. Tumor cells in all cases except one showed cytoplasmic or surface neutral or acidic mucin or both. Tumor cells stained positive for keratin (100% of cases), epithelial membrane antigen (100%), Leu-M1 (45%), B72.3 (85%), vimentin (35%), and carcinoembryonic antigen (25%). Electron microscopic studies of six cases showed epithelial differentiation in each. Seven patients (32%) were alive with no clinical disease at 3 to 31 months, one patient (4%) was alive with extensive local disease at 24 months, 11 patients (50%) died almost exclusively of local recurrence at 1 to 70 months, and three patients (14%) died of operative complications. It is concluded that SSC arises from peritoneal mesothelium but has epithelial phenotype. It can be morphologically differentiated from other conditions with similar laparotomy findings, such as malignant mesothelioma, benign papillary mesothelioma, cystic mesothelioma, and benign or borderline peritoneal serous tumors. The prognosis of SSC is poor, and most patients die of uncontrollable local disease.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; Female; Humans; Keratins; Lymphatic Metastasis; Membrane Glycoproteins; Middle Aged; Mucin-1; Ovarian Neoplasms; Peritoneal Neoplasms

Monoclonal antibodies (MAbs) to specific keratin subtypes were prepared and characterized by immunoblotting and immunohistochemical assays on human cell cultures and normal and malignant human tissues. Chain-specific MAbs to keratin 7 (RCK 105, OV-TL 12/30) and keratin 18 (RGE 53, RCK 106, CK18-2), as well as broadly cross-reacting keratin MAbs (RCK 102, OV-TL 12/5) could be shown to react with different types of human epithelial tissues and were therefore tested for their usefulness in the differential diagnosis of carcinomas. The two broad-spectrum antibodies stained virtually all of the more than 350 carcinomas tested, especially when combined, and distinguished them from most nonepithelial tumors. The keratin 18 MAbs distinguished adenocarcinomas (which are keratin 18 positive) from most squamous cell carcinomas (which are generally keratin 18 negative). The MAbs to keratin 7 could be shown to recognize specific subtypes of adenocarcinoma and could, for example, distinguish between ovarian carcinomas (keratin 7 positive) and carcinomas of the gastrointestinal tract (keratin 7 negative), or between transitional cell carcinomas (keratin 7 positive) and prostate cancer (keratin 7 negative). In general, malignancies showed the expected keratin reactivity pattern as concluded from the keratin pattern of its cell of origin or its type of differentiation. The use of an extended series of malignancies did, however, also illustrate that exceptions to this rule exist. For example, certain antibodies to keratin 18 stained tumor areas in squamous cell carcinomas of the lung. Also a certain percentage of tumors, which generally showed no keratin 7 expression, were positive with RCK 105 or OV-TL 12/30. On the other hand, a certain percentage of tumors, which were generally positive for keratin 7, did not show a staining reaction with these MAbs. Furthermore subtle differences between reactivity patterns of different MAbs recognizing the same keratin protein were observed, both in the normal and malignant human tissues, indicating that specific keratin epitopes may be masked in certain tissues and that unmasking of such epitopes can occur with malignant progression. This phenomenon may be of some use in a further subtyping of carcinomas, especially those of the gastrointestinal tract. Despite these exceptional staining patterns, the keratin MAbs described above have proved to be useful tools in the characterization of epithelial tumors in routine histopathology and

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunoblotting; Keratins; Lung Neoplasms; Male; Middle Aged; Ovarian Neoplasms; Prostatic Neoplasms

The distinction between serous neoplasms of the peritoneum in women and conventional mesothelioma can be difficult. In order to determine any significant immunohistochemical differences, formalin-fixed, paraffin-embedded sections of 10 peritoneal serous tumors (PST), 10 ovarian serous tumors (OST), and 10 epithelial mesotheliomas were evaluated with a panel of 10 antibodies directed against carcinoembryonic antigen (CEA: polyclonal, monoclonal), high molecular weight keratin (34 beta E12), low molecular weight keratin (35 beta H11), Leu-M1, TAG-72 (monoclonal antibody B72.3), human milk fat globulin (HMFG-2), vimentin, placental alkaline phosphatase (PLAP), and S-100 protein. The antibodies CEA, Leu-M1, and B72.3 had the most discriminatory value in differentiating serous tumors from mesothelioma. Eighty-five percent of PSTs and OSTs (17 of 20) were positive with CEA, Leu-M1, and/or B72.3. None of the mesotheliomas stained for CEA or Leu-M1; three mesotheliomas had very focal positivity with B72.3 (1% or less). Vimentin, PLAP, HMGF-2, keratin, and S-100 had no significant discriminatory value. Epithelial mucin was present in 80% of serous tumors, while the mesotheliomas lacked epithelial mucin. Leu-M1, CEA, and/or B72.3 positivity in a peritoneal tumor supports a diagnosis of serous tumor. However, since some PST do not stain for any of the three antibodies and the focal nature of positive reactions in some cases may be difficult to interpret, exclusion of mesotheliomas is enhanced by the use of mucin stains.

Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antibodies; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Diagnosis, Differential; Female; Gene Expression; Glycoproteins; GPI-Linked Proteins; Humans; Isoenzymes; Keratins; Membrane Glycoproteins; Mesothelioma; Middle Aged; Mucin-1; Mucins; Ovarian Neoplasms; Peritoneal Neoplasms; Pleural Neoplasms; S100 Proteins; Vimentin

Filed formalin-fixed paraffin blocks of 128 cases of epithelial neoplasms were selected for immunohistochemical study of keratin and vimentin expression. The results showed that 35.1% (45/128) of different carcinomas expressed vimentin. The immuno-positivity of vimentin in thyroid carcinomas, ovarian carcinomas, prostatic adenocarcinomas, pulmonary carcinomas and malignant mesotheliomas were 81.8%, 42.8%, 66.7%, 30.5% and 53.4%, respectively. Carcinomas of breast, kidneys, salivary glands, adrenal glands and nasopharyngeal carcinomas also showed various degrees of positive reaction. The results suggest that an immunohistochemical positive vimentin reaction does not exclude histopathological diagnosis of carcinomas. The significance and noticeable aspects of immunohistochemical methods in histopathological diagnosis are also discussed.

Topics: Carcinoma, Squamous Cell; Female; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Male; Mesothelioma; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prostatic Neoplasms; Thyroid Neoplasms; Vimentin

Twenty-two cases of keratin granulomas of the peritoneum associated with endometrioid adenocarcinoma with squamous differentiation of the endometrium, the ovary, or both, and with an atypical polypoid adenomyoma of the endometrium were reviewed. Follow-up data were available in 18 cases. Twelve patients were well and disease free 13 months to 15.2 years postoperatively; one patient died of unrelated disease 21 years postoperatively; three patients were tumor free with a short duration of follow-up; one patient, who had a stage Ic ovarian tumor, died of pulmonary embolism during the treatment of recurrent tumor 1 year after operation; and a final patient, who had been followed for 3 months after operation for stage IV disease, was alive with residual tumor. At least six patients with stage I carcinomas were treated with postoperative irradiation because the granulomas had raised a suspicion of advanced disease. Follow-up data on the patients in this series suggest that peritoneal keratin granulomas have no prognostic significance and should be distinguished from viable tumor implants on microscopic examination.

Topics: Adenocarcinoma; Adult; Aged; Endometriosis; Female; Follow-Up Studies; Granuloma; Humans; Keratins; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Peritoneal Diseases; Uterine Neoplasms

A monoclonal enzyme-linked immunosorbent assay (ELISA) was developed for the determination in biological fluids of cytokeratin 8, a potential marker for malignant diseases. Two monoclonal antibodies (MAbs), TS 3 and TS 4, with different epitope specificity, were selected from 4 cytokeratin-8 reactive antibodies. TS 3 was used for coating and TS 4 as HRP-conjugate, respectively. Antibodies were selected with the aim of optimizing the discriminatory capacity between cytokeratin 8 levels in sera from healthy persons and from patients with malignant diseases. In sera from healthy individuals the mean value was determined to be 3.1 +/- 2.3 ng/ml with an upper cut-off level of 7.8 ng/ml (+ 2 SD) using purified cytokeratin 8 as standard. Sera from patients with colon cancer and pancreatic cancer were found to have significantly elevated levels, showing a 4- to more than 10-fold increase compared with the normal level. In patients with ovarian cancer no significant elevation was seen. Cytokeratin 8 monitoring may be of value for patients with colon and pancreatic cancer.

Topics: Antibodies, Monoclonal; Colonic Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Male; Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms

A case of malignant mixed müllerian tumor of the ovary in a 57-year-old woman is reported along with the results of an immunohistochemical study. The tumor, measuring 16 x 10 x 9 cm, was composed predominantly of adenocarcinoma with a smaller amount of anaplastic carcinoma as an epithelial component and chondrosarcoma, liposarcoma, fibrosarcoma and rhabdomyoblasts as mesenchymal elements. Immunohistochemistry using paraffin sections demonstrated cytokeratin (CK) and epithelial membrane antigen (EMA), generally regarded as epithelial markers, not only in the epithelial component but also in chondrosarcoma cells. Vimentin and desmin, generally regarded as mesenchymal markers, were exhibited partly in carcinoma cells as well as in mesenchymal elements. Positive staining for S-100 protein was obtained not only in chondrosarcoma and liposarcoma cells, but also partly in adenocarcinoma cells. This intricate immunohistochemical picture reflected the histologic findings. It is noteworthy that both carcinoma cells and chondrosarcoma cells demonstrated simultaneous expression of CK, EMA, vimentin, desmin and S-100 protein. This somewhat unusual antigen expression by tumor cells may indicate a change in the nature of tumor cells due to microenvironmental factors.

Topics: Adenocarcinoma; alpha-Fetoproteins; Chondrosarcoma; Chorionic Gonadotropin; Desmin; Female; Fibrosarcoma; Humans; Immunohistochemistry; Keratins; Liposarcoma; Membrane Glycoproteins; Middle Aged; Mucin-1; Myoglobin; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Rhabdomyoma; S100 Proteins; Vimentin

The paper describes an image analysis technique for automated estimation of the epithelial percentage in standard paraffin tissue sections of invasive ductal breast cancers. Two staining procedures are evaluated: Feulgen (pararosanilin) and CAM 5.2-demonstrating the presence of cytokeratin 8 and 18-, both counterstained with naphthol yellow. In the technique, one image is recorded with a filter to visualize where the epithelium lies. This filter is chosen corresponding to the type of staining: it is yellow for Feulgen and blue for anti-cytokeratin CAM 5.2. To visualize where the stroma lies, the same image can be used for anti-cytokeratin CAM 5.2, whereas for Feulgen, a second image has to be recorded from the same microscope field with a blue filter. The image processing steps to determine the total tissue area comprise correction for shading, segmentation of the tissue area, and restoration of the segmented image by removal of small artefacts and closure of small tears in the tissue. The method for determination of the epithelial area consists of the following steps: correction for shading, gaussian blurring, segmentation of nuclei or epithelial cells, and editing of the segmented image by removal of small objects and closure of small spaces between the epithelial nuclei or cells. These image processing steps are compared to those for quantification of the epithelial percentage in gynecologic tumors of epithelial origin. For the Feulgen stain, the method is evaluated on 30 breast cancers of the ductal type (4 grade I, 12 grade II, and 14 grade III).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antibodies, Monoclonal; Breast Neoplasms; Coloring Agents; Epithelium; Female; Genital Neoplasms, Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Ovarian Neoplasms; Rosaniline Dyes; Uterine Neoplasms

An ovarian carcinoma cell line (OTN 11) was produced from the ascitic fluid of a patient with a moderately to well differentiated papilliferous cystadenocarcinoma of the ovary. The cell line was characterized using electron microscopy karyotyping, immunohistochemical techniques with monoclonal antibodies against keratins as epithelial markers, and the monoclonal antibodies OV-TL 3 and OC 125 as ovarian carcinoma markers. These techniques revealed the epithelial and adenocarcinomatous nature of the cell line and the presence of ovarian carcinoma-related surface markers. The adenocarcinomatous nature of the cell line also became apparent after heterotransplantation of cell suspensions into nude mice and nude rats, in which adenomatous tumor structures were formed. These xenografts had the same ultrastructural and immunohistochemical properties as the cell line. Despite the adenocarcinomatous character of the tumor the cultured cells release estradiol into the culture medium. We may conclude that OTN 11 is an ovarian carcinoma cell line which has retained highly differentiated functions, such as the production of an ovarian hormone.

Topics: Adult; Animals; Chromosome Aberrations; Cystadenoma; Estradiol; Female; Humans; Immunohistochemistry; Keratins; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Ovarian Neoplasms; Transplantation, Heterologous; Tumor Cells, Cultured

Using a battery of monoclonal antibodies, we investigated the cytokeratin pattern in the epidermides of 12 human ovarian mature cystic teratomas (MCTs) and compared them with those of infant, adult, and fetal skin. Histologically, two types of epidermal layers were identified in the MCTs, a mature layer and an immature layer. The mature layer was similar to the epidermis of infants and adults, while the immature layer resembled stratified nonkeratinizing and metaplastic squamous epithelium. The cytokeratin pattern of the histologically mature epidermis in MCT was either similar to that in infants and adults or was of the fetal type. The cytokeratin expression of the histologically immature epidermis in MCT also showed many similarities to the fetal cytokeratin pattern. We conclude that histologic maturity of the epidermis in MCT is not necessarily expressed by the cytokeratin pattern, which reflects the state of molecular rather than histologic differentiation. Since prognosis in germ cell tumors is usually related to the degree of tissue maturation, our observations raise the possibility that the cytokeratin profile may eventually prove to be a valuable prognostic tool in some of the neoplasms that contain epithelial elements.

Topics: Adult; Dermoid Cyst; Epidermis; Female; Fetus; Gestational Age; Humans; Immunochemistry; Keratins; Ovarian Neoplasms

An improved immunohistochemical determination of the cytokeratin profiles of epithelia and their neoplasms is possible using monoclonal antibodies that will either identify all 19 cytokeratins (AE1/3) or delineate specific subsets (35 beta H11, 34 beta E12, 34 beta B4 and Cam 5.2). Ovarian common "epithelial" tumors (CET) contain cytokeratin filaments. To determine the nature and differences in the cytokeratin profiles of ovarian CET, eight benign Brenner tumors, four serous cystadenofibromas, 28 mucinous tumors, 27 serous tumors and six endometrioid, five clear cell and five undifferentiated carcinomas, as well as nine normal ovaries were immunostained with the above five antibodies. AE1/3 staining was predominant, while Cam 5.2 and 35 beta H11 displayed the most frequent staining thereafter. Statistically significant staining differences were found between a number of tumor groups using the antibodies 35 beta H11, 34 beta E12 and Cam 5.2. In this study, all ovarian CET, except the benign Brenner tumors, displayed a predominantly low molecular weight cytokeratin profile. The same profile in the normal surface epithelium lends credence to the belief that these tumors are derived from this epithelium. A significant staining difference between some of the tumor types using some of the antibodies suggests a possible ancillary, diagnostic role of cytokeratin profiling in situations where exact tumor typing is difficult.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenofibroma; Adenoma; Antibodies, Monoclonal; Brenner Tumor; Carcinoma; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms

Paraffin-embedded material of 47 ovarian tumours primarily diagnosed as granulosa cell tumours, including 2 cases of juvenile granulosa cell tumour, were studied immunohistochemically for the presence of intermediate filament proteins, epithelial membrane antigen and tumour markers. Forty-one lesions, including the 2 juvenile granulosa cell tumours, were vimentin positive, while keratin and epithelial membrane antigen expression could not be detected. Six tumours primarily diagnosed as poorly differentiated malignant granulosa cell tumours were vimentin negative, showed a mild to moderate positivity for keratin and intense positivity with the anti-epithelial membrane antigen antibody. These latter tumours were therefore classified as undifferentiated ovarian carcinomas, corresponding to their significantly poorer prognosis and shorter survival when compared with the granulosa cell tumours. Two of these six tumours were positive for carcino-embryonic antigen. Two small cell carcinomas of the ovary studied in addition expressed keratin in a proportion of tumour cells while no epithelial membrane antigen or vimentin was detectable. None of the tumours tested for alpha-fetoprotein, human chorionic gonadotrophin, human placental alkaline phosphatase and human placental lactogen, were positive. The data indicate the value of antibodies directed against intermediate filament proteins and epithelial membrane antigen to distinguish granulosa cell tumours from poorly differentiated carcinomas, a worthwhile distinction considering the much better prognosis of granulosa cell tumours.

Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Granulosa Cell Tumor; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Neoplasm Proteins; Ovarian Neoplasms; Vimentin

Small cell carcinoma of the ovary is a rare, poorly understood aggressive tumor of young women, associated with paraendocrine hypercalcemia in two-thirds of the cases. Immunohistochemical staining of 15 small cell carcinomas, one-third of which were associated with hypercalcemia, 15 adult granulosa cell tumors, 15 juvenile granulosa cell tumors, and 5 Sertoli cell tumors, was performed with the use of antibodies against cytokeratins (AE-1/AE-3, CAM 5.2, 902), epithelial tumor-associated antigens (B72.3, epithelial membrane antigen [EMA]), vimentin, S-100, neuron-specific enolase (NSE), lysozyme, parathyroid hormone, and chromogranin-A in an attempt to define histogenetically this tumor type. One-third of the small cell carcinomas were positive for EMA, whereas all of them were negative for B72.3 and S-100. In contrast, one-third of the granulosa cell tumors were positive for S-100 and all of them were negative for EMA and B72.3. One of five Sertoli cell tumors were positive for EMA and two were positive for B72.3, but all were negative for S-100. Differences existed in the frequency, intensity, and/or pattern of staining for cytokeratin, vimentin, lysozyme, and NSE among the various tumor types. A single small cell carcinoma from a patient with hypercalcemia stained focally for parathyroid hormone, whereas all 30 granulosa cell tumors and 4 of 5 Sertoli cell tumors were nonreactive. Chromogranin-A staining was noted in four of five small cell carcinomas, none of ten granulosa cell tumors, and two of five Sertoli cell tumors. These immunohistochemical findings, as well as previous light and electron microscopic data, do not clearly indicate any specific cell as the cell of origin of the ovarian small cell carcinoma.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Small Cell; Chromogranin A; Chromogranins; Female; Granulosa Cell Tumor; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; S100 Proteins; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Primary papillary serous carcinoma arising from the peritoneal surface (serous surface papillary carcinoma; SSPC) is a distinctive neoplasm with a histomorphologic resemblance to serous ovarian papillary carcinoma (SOPC). To determine if these tumors are similar antigenically, we studied 13 examples of SSPC and 31 of SOPC immunohistochemically. Antibodies to several determinants known to occur in the Müllerian epithelium were employed. Both neoplasms were uniformly positive for cytokeratin and epithelial membrane antigen (EMA); in addition, SSPC and SOPC were similar in quantitative and qualitative reactivity for B72.3 antigen, carcinoembryonic antigen, Leu M1, CA-125 antigen, LN1, LN2, MB2, S100 protein, placental alkaline phosphatase, and amylase. Residual nonneoplastic mesothelium failed to express any of these antigens except for cytokeratin, EMA, and CA-125. The clinical behavior of SSPC was similar to that of high-stage SOPC; all patients with adequate follow-up died of their tumors. These results suggest that SSPC and SOPC are analogous lesions, with respect to their cellular differentiation. Moreover, it would appear that both neoplasms display only a limited immunophenotypic homology to the mesothelium.

Topics: Adult; Aged; Aged, 80 and over; Amylases; Antigens, Neoplasm; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Ovarian Neoplasms; Peritoneal Neoplasms; Proteins

Germ cell neoplasms were reviewed for the investigation of a mesenchyme-like component of yolk sac tumor (YST) characterized by spindle cells with few mitoses in a myxoid, vascular background. Nineteen YSTs with this pattern were identified. The mesenchyme-like component of these YSTs appeared to derive from the epithelial elements of YST, since cytokeratin as well as vimentin positivity occurred in the spindle cells of the mesenchyme-like areas and foci of epithelial-spindle cell transition were present. In some cases the mesenchyme-like component showed differentiated mesenchymal elements (usually skeletal muscle). Similar features were identified in 13 chemotherapy-treated cases of YST that consisted only of this mesenchyme-like component. The mesenchyme-like component of YST appears to represent a chemoresistant, pluripotential cell population arising from metaplasia of YST epithelium; it may give rise to sarcomas occurring in some patients with treated germ cell tumors.

Topics: alpha-Fetoproteins; Female; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Neoplasms; Mesonephroma; Ovarian Neoplasms; Testicular Neoplasms; Vimentin

An epithelial ovarian carcinoma from a patient with progressive disease who had received combination chemotherapy was established as a cell line and characterized. The doubling time of the cell line was seven days. The subcutaneous inoculation with 10(6) cells into an athymic nude mouse produced a 5 X 5-mm nodule with a histology similar to that of the original tumor. The malignant epithelial cells were aneuploid and varied in chromosome numbers from 50 to 115; double minutes were present in 25% of the cells. Antibodies specific for keratin showed a dense filamentous keratin network within the cells. No estrogen receptors were identified by immunocytochemistry. A heterogeneous tumor population in the sixth passage was suggested by flow cytometric analysis. This cell line may be a useful in vitro model for studying the biology and mechanisms of radiation and/or chemotherapy resistance of ovarian carcinomas.

Topics: Animals; Cell Line; Cystadenocarcinoma; Female; Humans; Keratins; Mice; Mice, Nude; Middle Aged; Neoplasm Transplantation; Ovarian Neoplasms; Receptors, Estrogen; Transplantation, Heterologous; Tumor Cells, Cultured

Ovarian endometrioid carcinomas resembling sex cord-stromal tumors (ECSCSs) may simulate Sertoli cell tumors, Sertoli-Leydig cell tumors (SLCTs), and adult granulosa cell tumors (AGCTs), both clinically and pathologically. Differing clinical features and histologic findings are almost always successful in distinguishing these tumor types, although in some cases the differential diagnosis is difficult. Immunohistochemical staining of 17 ECSCSs, 14 Sertoli cell tumors or SLCTs, and 15 AGCTs was performed with the use of antibodies against cytokeratins (AE1/AE3, 902, and CAM 5.2), epithelial tumor-associated antigens (EMA, OM-1, B72.3, and carcinoembryonic antigen B1.1), vimentin, S-100, neuron-specific enolase, and lysozyme to determine the immunohistochemical profile of each tumor type and to define further the nature of the sex cord-like components in ECSCSs. All 17 ECSCSs, none of the 15 AGCTs, and one of 14 Sertoli cell tumors or SLCTs stained with EMA. Staining for OM-1 was almost as helpful diagnostically, with positive results for 15 of 17 ECSCSs, 0/15 AGCTs, and 1/14 Sertoli cell or SLCTs. Antikeratins were immunoreactive with all the ECSCSs as well as some of the AGCTs and Sertoli cell tumors or SLCTs. The B72.3 and B1.1 were immunoreactive with some ECSCSs and Sertoli cell tumors, but were nonreactive with AGCTs. Neuron-specific enolase was demonstrated in 11 of 17 ECSCSs, two of 14 Sertoli cell tumors or SLCTs, and 0 of 15 AGCTs. Vimentin, S-100, and lysozyme were least helpful in the differential diagnosis. These studies suggest that an immunohistochemical approach may be useful in the differentiation of ECSCSs and sex cord-stromal tumors. Furthermore, it supports the conclusion that the sex cord-like cells in ECSCSs are not Sertoli or granulosa cells, but cells of surface epithelial type growing in architectural patterns similar to those of sex cord-stromal tumors.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Diagnosis, Differential; Endometriosis; Female; Granulosa Cell Tumor; Humans; Immunohistochemistry; Keratins; Leydig Cell Tumor; Lysosomes; Male; Ovarian Neoplasms; Phosphopyruvate Hydratase; S100 Proteins; Sertoli Cell Tumor; Testicular Neoplasms; Vimentin

Eighty five ovarian epithelial and non-epithelial tumours were studied by peroxidase histochemical staining for their reactivity with six monoclonal human milk fat globule (HMFG) antibodies, peanut agglutinin (PNA) lectin, and a monoclonal cytokeratin antibody. HMFG IIIC12 and cytokeratin antibodies distinguished epithelial from non-epithelial tumours. The staining patterns of mucinous and serous tumours were essentially different from each other; poorly differentiated anaplastic carcinomas showed similar antigenic content to that of the serous cystadenocarcinomas. Furthermore, staining with PNA lectin and HMFG antibodies was useful in distinguishing clear cell carcinomas from other malignant epithelial tumours of the ovary.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Cystadenocarcinoma; Epitopes; Female; Granulosa Cell Tumor; Humans; Immunoenzyme Techniques; Keratins; Lectins; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; Peanut Agglutinin

A primary culture of serous cystadenocarcinoma of the ovary was used to study the expression of intermediate filament proteins and the deposition of basal lamina proteins. It was found that cells grown on type I and IV collagens or in collagen gels failed to express vimentin, which was readily demonstrable in cultures of the same cells grown on plastic or glass. Furthermore cells grown in collagen gels formed colonies demonstrating a cystic architecture. Unlike what is commonly observed on glass or plastic, where laminin and fibronectin are deposited as disorganized fibrils in the extracellular space, in or on collagen these proteins appear solely at the interface between the epithelial cells and matrix. The results suggest that the extracellular matrix influences the cytoskeletal organization of the intermediate filaments and determines cell polarity. They confirm that collagen substrates permit epithelial cell cultures to progress toward a more differentiated state.

Topics: Basement Membrane; Cell Count; Cell Division; Collagen; Cystadenocarcinoma; Cytoskeleton; Epithelium; Extracellular Matrix; Female; Fibronectins; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Laminin; Membrane Proteins; Middle Aged; Ovarian Neoplasms; Tumor Cells, Cultured; Vimentin

A human ovarian Brenner tumor presenting a wide spectrum of benign and malignant histologic features was studied for its patterns of intermediate filament expression. All epithelial elements of the tumor, regardless of their morphologic type, contained cytokeratins as their only intermediate filament component. Differences were detected, however, between tumor nests that displayed transitional epithelium and those with squamoid features. These differences were manifested by the presence of cytokeratin 18, in the former type only, and by the abundance of cytokeratins 10/11 in the latter. We also detected mixed epithelial nests in which both features were present, suggesting that the transitional epithelium transforms in polar fashion into squamous epithelium. Examination of cytokeratin patterns found in urothelium and in the surface epithelium of the ovary pointed to certain differences from the Brenner tumor epithelia. The significance of these latter findings with regard to cellular transformation and histogenesis of the Brenner tumor are discussed.

Topics: Antibodies, Monoclonal; Brenner Tumor; Cytoskeletal Proteins; Desmin; Desmoplakins; Desmosomes; Epithelium; Female; Fluorescent Antibody Technique; Humans; Keratins; Membrane Glycoproteins; Middle Aged; Ovarian Neoplasms; Ovary; Urinary Bladder Neoplasms; Vimentin

The authors studied 79 common epithelial ovarian tumors in order to ascertain the intermediate filament profiles in formalin-fixed and methacarn-fixed, paraffin-embedded surgical pathology materials. Ultra-structural correlations were attempted with several tumors. All categories of common benign and malignant epithelial tumors were examined. Antibodies used in the study included antikeratins (AE1/AE3, 35BH11, 34BE12), carcinoembryonic antigen (CEA), and vimentin. All ovarian epithelial tumors expressed keratin in uniform fashion, except high molecular weight keratin (34BE12) which was focal. Vimentin was coexpressed with cytokeratins in 42% of serous carcinomas, 71% of endometrioid carcinomas, and 7% of clear cell carcinomas. Vimentin decoration in serous carcinoma was very focal, whereas endometrioid decoration tended to involve larger areas, similar to uterine-based endometrial adenocarcinoma. Mucinous, Brenner, and solid (not otherwise specified) ovarian tumors were positive only for cytokeratin. Carcinoembryonic antigen luminal staining was present in 52% of serous carcinomas and 87% of mucinous carcinomas. Whereas there are distinct differences in intermediate filament expression among ovarian carcinomas, these differences do not allow for specific categorization of ovarian neoplasms because there is some overlap of intermediate filament expression. In order to differentiate ovarian carcinoma from other carcinomas and mesothelioma, other methods of study would be necessary in addition to intermediate filament profiles, such as CEA immunohistochemistry, mucin histochemistry, and ultrastructural study.

Topics: Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Ovarian Neoplasms; Vimentin

An immunocytochemical investigation has been performed on 83 common epithelial tumours of the ovary, to ascertain their capability of expressing vimentin in addition to cytokeratins. Our results demonstrate that vimentin coexpression is related to the tumour histotype and -to a lesser extent- to the degree of differentiation of malignant variants. Indeed, most serous tumours (80%), some endometrioid adenocarcinomas, and all the clear cell carcinomas investigated exhibited a variable number of neoplastic cells co-synthesizing the two distinct intermediate filament (IF) proteins, whereas only one of 29 mucinous tumours and none of the Brenner tumours displayed vimentin-immunoreactive cells. Moreover, in serous and endometrioid carcinomas, the expression of vimentin was related to the degree of tumour differentiation, being consistently identifiable in the better differentiated cases. The immunocytochemical findings of a parallel investigation on IF expression in the ovarian coelomic epithelium and in the müllerian-derived epithelia of the female genital tract allowed us to ascertain that ovarian epithelial tumours (with the possible exception of poorly differentiated carcinomas) maintain the pattern of IF expression typical of the normal epithelia. This investigation emphasizes the usefulness of IF typing as a tool for the more precise characterization of the origin and differentiation of human neoplasms.

Topics: Adenocarcinoma; Brenner Tumor; Carcinoma; Cystadenocarcinoma; Cystadenoma; Endometriosis; Epithelium; Female; Genitalia, Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Ovary; Vimentin

The immunoprofiles of 121 germ cell and trophoblastic neoplasms were defined, using a battery of antibodies against cytokeratin (CK), vimentin (VIM), epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), S-100 protein, leukocyte common antigen (LCA), UCHL-1, LN-2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), chromogranin A, Leu-7, alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), and the beta subunit of human chorionic gonadotropin (BHCG). In addition to 85 neoplasms of testicular origin, the cases included eight ovarian germ cell tumors and 28 extragonadal neoplasms. All tissues had been subjected to formalin fixation and paraffin embedding. Similar immunoreactivity patterns were seen in gonadal and extragonadal neoplasms, gestational and nongestational choriocarcinomas, components of mixed germ cell tumors and their pure counterparts, and metastatic and primary lesions. Placental alkaline phosphatase was a sensitive marker of germ cell differentiation, and expression of this marker in the absence of EMA appeared to be a staining pattern unique to germ cell tumors. Both LCA and S100 were absent in neoplastic germ cells, and thus were useful in differentiating these tumors from malignant lymphoma and malignant melanoma, respectively. Cytokeratin was helpful in distinguishing seminomas/dysgerminomas from nonseminomatous germ cell tumors, although 10% of seminomas showed focal or diffuse cytokeratin reactivity. Finally, 75% of all germ cell neoplasms displayed NSE, calling the specificity of this determinant into question.

Topics: Alkaline Phosphatase; alpha 1-Antitrypsin; alpha-Fetoproteins; Antibodies, Monoclonal; Antigens, Differentiation; Carcinoembryonic Antigen; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Histocompatibility Antigens; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Male; Membrane Glycoproteins; Mucin-1; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Peptide Fragments; Phenotype; Placenta; Pregnancy; Testicular Neoplasms; Trophoblastic Neoplasms; Vimentin

Twenty-six intracranial germ cell tumours (11 germinomas, 10 teratomas, 2 endodermal sinus tumours, 1 teratocarcinoma, and 2 undifferentiated embryonal carcinomas) and 26 gonadal germ cell tumours (13 testicular seminomas, 2 ovarian dysgerminomas, 9 ovarian teratomas, and 2 myometrial choriocarcinomas) were studied by immunoperoxidase with monoclonal antibodies (MAbs) against epithelial membrane antigen (EMA), cytokeratin, and vimentin. Typical tumour cells in three of the 11 germinomas (two of the latter being situated in the posterior fossa) expressed both EMA and cytokeratin, whereas those in the seminomas and dysgerminomas did not. In one seminoma, a few multinucleated giant cells expressed cytokeratin. In three of seven germinomas, vimentin-positive tumour cells were found, but all seminomas and dysgerminomas were negative. In the other forms of intracranial and gonadal germ cell tumours, epithelial and mesenchymal elements displayed the expected patterns of immunoreactivity to the respective determinants. The immunoperoxidase differences between the intracranial germinomas and their gonadal equivalents indicate that, in the former, early epithelial or mesenchymal differentiation of the primordial germ cells may be present. The findings draw attention to the heterogeneous cellular composition of these otherwise morphologically homogeneous-appearing tumours and, especially in the posterior fossa, to their transitional links to the immature teratomas.

Topics: Adolescent; Adult; Antigens, Neoplasm; Brain Neoplasms; Child; Child, Preschool; Choriocarcinoma; Dysgerminoma; Epitopes; Female; Humans; Immunoenzyme Techniques; Infant; Keratins; Male; Membrane Glycoproteins; Mesonephroma; Middle Aged; Mucin-1; Ovarian Neoplasms; Teratoma; Testicular Neoplasms; Uterine Neoplasms; Vimentin

Eighteen examples of serous carcinoma arising in a background of a serous tumor of low malignant potential (SLMP with microinvasion) are reported. Nine of the 18 patients were less than 35 yr of age, and 5 were pregnant. In one patient, the microinvasive tumor was bilateral. The contralateral ovary had a serous tumor of low malignant potential (SLMP) in 9 additional women. Twelve patients presented with Stage I tumors, while 6 (33%) had tumors in Stages II and III. The tumors in all patients below the age of 30 were Stage I, and all three patients with Stage III tumors were older than 50. Two cell types were identified in all 18 tumors. The more dominant cell type was similar to those found in the typical SLMP tumors. The second cell type was larger with abundant eosinophilic cytoplasm, round nuclei, and prominent nucleoli; these were the cells that invaded the stroma of the papillary stalks in every case. Only one patient died of her disease, and she had Stage III tumor with massive ascites at presentation. All other patients are alive and well without evidence of disease from 2.5 to 5.5 yr after the diagnosis.

Topics: Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Cystadenoma; Female; Follow-Up Studies; Humans; Hysterectomy; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasm Invasiveness; Ovarian Neoplasms; Ovariectomy; Pelvic Neoplasms; Peritoneal Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic

Ten cases of extrauterine malignant mixed mesodermal tumors (MMMTs), nine ovarian, and one pelvic, are presented. One patient had a purely epithelial primary ovarian tumor and MMMT in her recurrent tumors. All the other patients had MMMT in their primary and recurrent tumors. Eight patients had heterologous MMMT including cartilage, striated muscle, and adipose tissue in one case. Two patients had homologous MMMT. All cases presented with metastases involving abdominal organs that were either MMMT or epithelial neoplasms and MMMT. Five patients had recurrent tumors, one extensively involving the spleen. In all recurrent tumors, the mesenchymal components were considerably more abundant than in the primary tumors. Immunohistologic studies of intermediate filaments were performed in seven cases, revealing cytokeratin-positive epithelial structures, vimentin-positive mesenchymal (including cartilaginous) structures, as well as coexpression of cytokeratin and vimentin in anaplastic and giant tumor cells in some cases. Some anaplastic spindle cells, which on routine stains were suggestive of stromal cells, stained positive for cytokeratin, thus identifying their epithelial nature. Desmin staining performed in five cases showed positive staining of rhabdomyoblasts in only one case. Myoglobin staining performed in seven cases was positive in four. The histogenesis from primitive müllerian structures and the natural history of these uncommon neoplasms are discussed in light of the pathological and immunohistochemical data presented.

Topics: Aged; Aged, 80 and over; Carcinoma, Papillary; Desmin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Myoglobin; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Pelvic Neoplasms; Vimentin

The expression of the intermediate filaments cytokeratin and vimentin were studied immunohistochemically in a series of ovarian sex cord-stromal tumours (26 adult and juvenile granulosa cell tumours, 11 thecomas, six fibromas, three Sertoli-Leydig cell tumours and 1 sex cord tumour with annular tubules). Contrary to previous reports, granulosa cell tumours expressed cytokeratins as well as vimentin. Thecomas and fibromas expressed vimentin only. In Sertoli-Leydig cell tumours and the sex cord tumour with annular tubules, both cytokeratins and vimentin were detected. Correlative studies in adult ovaries showed that patterns of expression in non-neoplastic granulosa, thecal and stromal cells correspond to their neoplastic counterparts. Investigation of fetal ovaries demonstrated that these patterns of intermediate filament expression exist from relatively early stages of development. Ovarian surface epithelium and rete ovarii, like granulosa cells, co-expressed cytokeratin and vimentin. The demonstration of cytokeratins in granulosa cells and the reported presence of desmosomes and tonofilaments, suggests the epithelial nature of these cells although not clarifying their histogenesis. The presence of both these intermediate filaments in granulosa and Sertoli-Leydig cell tumours as well as in some ovarian carcinomas which may mimic them, limits their value in differential diagnosis between these tumour groups.

Topics: Adult; Cytoskeleton; Female; Fibroma; Granulosa Cell Tumor; Humans; Intermediate Filaments; Keratins; Leydig Cell Tumor; Ovarian Neoplasms; Ovary; Thecoma; Vimentin

Four clonal cell lines of two types were established from a heterotransplantable mixed mesodermal tumor of the human ovary. Biologic properties of these cell lines (designated CS-C1, CS-S1, CS-S2, and CS-S3) were examined. Cells of one line (CS-C1) had an epithelioid shape and grew in monolayers (C-type). The cells showed alkaline phosphatase activity, stained positively with antikeratin antiserum, and had an ultrastructure with carcinomatous characteristics. Cells of the other three cell lines (CS-S1, CS-S2, and CS-S3) had an irregular shape and grew in multilayers (S-type). Most of the cells did not show alkaline phosphatase activity. They stained, not with antikeratin antiserum, but in fibrillar array with antifibronectin antiserum. Their ultrastructure had sarcomatous characteristics. By low cell density cultures, S-type sublines arose from CS-C1 cell line, but no C-type sublines arose from CS-S1 cell line. These findings may support the theory of the combination tumor as the cytogenesis of mixed mesodermal tumor of the ovary; they also suggest the conversion of carcinomatous cells to sarcomatous cells.

Topics: Carcinoma; Cell Line; Female; Humans; Karyotyping; Keratins; Microscopy, Electron; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Sarcoma; Tumor Cells, Cultured

170 germ cell tumours of childhood and adolescence were studied by light microscopy and immunohistochemistry. The male-to-female ratio was 1:1.3. 52 (30.6%) tumours were benign (mature teratoma), 30 (17.6%) potentially malignant (immature teratoma), and 88 (51.8%) unequivocally malignant. The main locations were ovary, testis and sacrococcygeal region. 92 tumours were located in a gonad, 78 tumours in extragonadal sites (ratio: 1.2:1). Of the frankly malignant tumours 40 were yolk-sac tumours (YST) and an additional 19 tumours of more than one histological type contained a YST component. Therefore, 67% of the malignant tumours had a YST component. Children with immature teratoma and pure YST showed the lowest median age (5 and 24 months, respectively), while children with germinomas of various locations had the highest median age (153 months). A festoon pattern was the predominant histological feature in all YST and in the YST component of mixed germ cell tumours. Hyaline globules were found in 33/37 YST and in 16/17 YST components. Immunohistochemically, alpha 1-fetoprotein (AFP) was demonstrated in 18/22 YST and in 6/7 YST components of mixed germ cell tumours. Hyaline globules were mostly AFP-negative (only 5 cases with AFP-positive globules in addition to many AFP-negative globules). In 3 cases beta-HCG-positive giant cells were seen. In most YST prekeratin intermediate filaments could be demonstrated in the epithelial cells. Follow-up data, available from 51 cases of YST and tumours with YST components showed disease-free survival in 37 cases (72.5%). 10 patients (19.6%) died of disease, and 4 patients (7.8%) are living with disease. The comparably high rate of survivors reflects the effectiveness of modern therapy, particularly polychemotherapy, in addition to surgery.

Topics: Adolescent; alpha-Fetoproteins; Child; Child, Preschool; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Dysgerminoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Infant; Keratins; Male; Mesonephroma; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Peptide Fragments; Protein Precursors; Sacrococcygeal Region; Teratoma; Testicular Neoplasms

Topics: Antigens, Neoplasm; Carcinoma; Cytoskeletal Proteins; Desmoplakins; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Membrane Proteins; Ovarian Neoplasms; Vimentin

In the present study we describe the establishment and characteristics of a new human tumor cell line (OV-1063) positive for carcinoembryonic antigen (CEA) originating from ovarian metastatic tumor cells. Analysis of the cultured cells during their in vitro adaptation period revealed while the primary culture exhibited a low proportion of CEA-positive cells, this proportion increased with culture passages and eventually more than 90% of the cells in the established line were CEA-positive. Thus, during the period of adaptation to in vitro growth, a selection for CEA-positive cells took place but the amount of CEA secreted per each positive cell seemed to be constant. Several tumor-associated characteristics were found positive on the established OV-1063 cell line. The in vitro growing cell line exhibited an abnormal chromosome pattern with a near-trisomy karyotype for some chromosomes, colony formation in soft agar as well as positive staining with a monoclonal antibody B38.1. Culture supernatants of the OV-1063 cells contained significant amounts of CEA as well as CA-125 antigen which is an ovarian-carcinoma-associated antigen.

Topics: Agar; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Ascitic Fluid; Carcinoembryonic Antigen; Cell Line; Culture Media; Cystadenocarcinoma; Female; Humans; Karyotyping; Keratins; Microscopy, Phase-Contrast; Middle Aged; Ovarian Neoplasms

Topics: Female; Humans; Immunoenzyme Techniques; Keratins; Leydig Cell Tumor; Ovarian Neoplasms; Sertoli Cell Tumor

The authors investigated the expression of keratin, carcinoembryonic antigen (CEA), and an epithelial marker derived from milk fat globule membranes in 12 mesotheliomas and 100 diverse adenocarcinomas with immunohistochemical methods. The authors employed a monoclonal antibody to keratin designated as AE1, as well as the following commercially available antisera: rabbit anti-whole human keratin, rabbit anti-CEA, and a monoclonal antibody to an epithelial factor designated as MFG-2. Expression of keratin was found in all the mesotheliomas and adenocarcinomas with antibody AE1 as well as with the rabbit antiserum; CEA was detectable in 65% of the adenocarcinomas but two mesotheliomas also reacted weakly. With antibody MFG-2, positive results were obtained in 85% of the adenocarcinomas and in none of the mesotheliomas. All of 64 (100%) breast-, lung- and ovary-derived adenocarcinomas immunostained positively with antibody MFG-2. This is of particular significance because pulmonary and ovarian adenocarcinoma frequently may be indistinguishable clinically and histologically from epithelial mesothelioma. The authors conclude that antikeratin antibodies are not useful in the distinction of adenocarcinoma from mesothelioma. Because of its greater sensitivity and specificity, MFG-2 is superior to CEA in this differential diagnosis.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Breast Neoplasms; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Male; Mesothelioma; Ovarian Neoplasms; Staining and Labeling

Topics: Adult; Aged; Carcinoembryonic Antigen; Carcinoma, Papillary; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Middle Aged; Ovarian Neoplasms; Ovary

The authors investigated the presence and distribution of keratin in germ cell tumors using a rabbit-anti-keratin antiserum and a monoclonal antikeratin antibody--which is specific for keratin classes of 40, 50, and 56.5 kdaltons--by various immunohistochemical methods on frozen sections, alcohol-fixed, and formalin-fixed paraffin-embedded tissues. Thirty-four germ cell tumors were studied. These were the following: 18 seminomas, 10 embryonal carcinomas, 2 teratocarcinomas, 3 yolk sac tumors and 1 choriocarcinoma. All seminomas, including four poorly differentiated (so-called anaplastic seminomas), gave negative results, regardless of the method employed. Embryonal carcinoma, the epithelial component of the teratocarcinoma, the yolk sac tumors, and choriocarcinoma were at least focally positive for keratin. The monoclonal antibody provided a cleaner background and stronger staining than the rabbit-anti-total-human-epidermal-keratin antibody. Best results were obtained from fresh-frozen sections or alcohol-fixed, paraffin-embedded materials. Formalin-fixed, nonseminomatous tumors, when predigested with trypsin and incubated overnight with primary antibody, gave no false-negative results but staining was often focal. The authors' results agree with the reported absence of detectable keratin in primordial germ cells of the normal testis, and with prevailing concepts of the histogenesis of germ cell tumors. These results indicate that the presence or absence of keratin by immunocytochemical methods can be helpful in distinguishing seminoma from embryonal carcinoma.

Topics: Antibodies, Monoclonal; Choriocarcinoma; Diagnosis, Differential; Dysgerminoma; Female; Frozen Sections; Humans; Immunologic Techniques; Keratins; Male; Mesonephroma; Ovarian Neoplasms; Pregnancy; Teratoma; Testicular Neoplasms; Uterine Neoplasms

A comparison of five immunohistochemical methods for the demonstration of keratins in human ovarian neoplasms using affinity-purified polyclonal rabbit antibody was made. The use of indirect immunofluorescence on frozen sections briefly fixed in acetone was found to be the most sensitive method and demonstrated keratin in all 14 primary and 1 metastatic ovarian epithelial neoplasms studied. Protein A-peroxidase, peroxidase--antiperoxidase (PAP), indirect peroxidase, or the avidin--biotinylated peroxidase complex (ABC) methods applied to formalin-fixed tissues were less sensitive and led to false negative results in 9 of 15, 1 of 15, 8 of 15, and 6 of 15 cases, respectively. A single case of dysgerminoma failed to reveal keratin by any method.

Topics: Female; Fluorescent Antibody Technique; Formaldehyde; Freezing; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms

In an attempt to further characterize benign, proliferating, and malignant Brenner tumors, immunoperoxidase staining for prekeratin was undertaken in a group of these neoplasms as well as in a variety of histologically different tumors of the ovary. All Brenner tumors reacted positively for prekeratin, whereas none of the other epithelial or sex cord-stromal tumors of the ovary stained. On the basis of these findings, we conclude that prekeratin might be a useful marker for differentiating malignant Brenner tumors from histologically similar, poorly differentiated ovarian neoplasms.

Topics: Brenner Tumor; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Ovarian Neoplasms; Protein Precursors

We studied the expression of cytoskeletal intermediate filaments in different types of ovarian and uterine sarcomas and carcinomas. In both uterine and ovarian leiomyosarcomas, in endometrial stromal sarcomas, and also in ovarian sarcomas, most tumor cells appeared to be positive for desmin, the muscle type of intermediate filament protein. In most of the tumors, vimentin was present only in some neoplastic cells and in the vascular endothelia. Interestingly, both uterine and ovarian malignant mixed mesodermal tumors appeared to express several types of intermediate filaments, most of the stromal cells being positive for vimentin or desmin, and the epithelial component expressing keratin. The results show that most of the sarcomatous tumors of the ovary and uterus express mainly muscle type of intermediate filament protein. The results also demonstrate the ability of cells of mesodermal origin to express epithelial cytoskeleton markers--cytokeratins.

Topics: Adenocarcinoma; Cystadenocarcinoma; Desmin; Female; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Leiomyosarcoma; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Sarcoma; Uterine Neoplasms; Vimentin

Cytokeratins are one of the intermediate cytoplasmic filaments which contribute to the cytoskeleton. Keratins have recently been demonstrated in normal and neoplastic tissues as well as in human cell lines. It has been suggested that the cellular location of keratin may reflect tissue-specific or epithelial type differentiation. Twenty-three examples of human ovaries containing the full spectrum of epithelial proliferations from inflammatory reactive processes to malignant neoplasia were studied for the cellular distribution of cytokeratin using antisera to human keratin. Nineteen cases contained immunoreactive keratin which was limited to the epithelial cells: 2/2 inflammatory, 8/10 benign tumors, 5/7 borderline tumors, 4/4 carcinomas. There was marked regional heterogeneity in keratin expression such that adjacent morphologically-identical cells could be functionally distinguished by the immunoreactive staining. The predominant cellular localization of keratin varied between histological tumor types in the benign neoplasms: serous = apical, subciliary; endometrioid = apical; mucinous = basal. This pattern was lost in the cytological progression to borderline and malignant tumors. In borderline tumors, the most intense reactivity was noted in areas of cellular atypia and proliferation. In borderline and malignant tumors, keratin was usually present in basal cytoplasmic regions contiguous with stroma.

Topics: Carcinoma; Cell Division; Epithelium; Female; Humans; Keratins; Ovarian Neoplasms; Tissue Distribution

In this study the surface ultrastructure of 28 cystic ovarian teratomas was examined to determine their morphological appearance and the relation to biological behavior. The squamous epithelium of cystic tumors showed abnormal maturation and keratinization of surface cells with keratinous flakes occasionally in polypoid configurations. The respiratory epithelium showed an abundance of microvillous and ciliated cells, areas with disorganized surface structures were also seen. Piling up of squamous cells in heaps, piles, cauliflower- or onion-like arrangements were seen in lesions histologically regular. This study showed a distinct difference in surface ultrastructure as compared to ovarian cystadenomas emphasizing the difference in development. Surface ultrastructural studies also were useful in deciding the nature of histologically indeterminable lesions as well as in revealing areas of malignant potential.

Topics: Cilia; Dermoid Cyst; Epithelium; Female; Humans; Keratins; Microscopy, Electron; Microscopy, Electron, Scanning; Microvilli; Ovarian Neoplasms

The cytoskeletal proteins of cultured normal human mesothelial cells were found to consist of six major components, including actin, vimentin, the 40 kd keratin and the 44, 52 and 55 kd proteins, plus a minor 46 kd protein. Two-dimensional gel electrophoresis, peptide mapping and immunoprecipitation tests showed that the 40-55 kd mesothelial proteins are a family of keratins distinct in size, charge or peptide map from the "epidermal keratins" synthesized by cultured keratinocytes. Unique combinations of keratins from the epidermal and mesothelial keratin families were found to be synthesized by cultured bladder, esophageal, conjunctival, mammary, exocervical and ovarian surface epithelial cells. Mesothelial cells were the only epithelial cell type that synthesized vimentin at more than trace levels. We have also found that many carcinoma cell lines express keratins different from those of their cell type of origin.

Topics: Actins; Cell Line; Electrophoresis, Polyacrylamide Gel; Epithelium; Female; Humans; Intermediate Filament Proteins; Keratins; Molecular Weight; Ovarian Neoplasms; Peptide Fragments; Vimentin

Topics: Carcinoma, Squamous Cell; Cell Nucleolus; Cell Nucleus; Collagen; Dermoid Cyst; Epithelial Cells; Epithelium; Female; Fibroma; Humans; Keratins; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms

Topics: Dermoid Cyst; Female; Granuloma; Humans; Keratins; Laparoscopy; Medical Records; Neoplasms; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Peritoneum; Teratoma