bromochloroacetic-acid and Endometrial-Neoplasms

A collision tumor is defined by the presence of two separate masses in one organ, which are pathologically distinct. We described a 70-yr-old patient who complained of abnormal vaginal bleeding with a collision tumor of the uterine corpus. The patient received total hysterectomy, bilateral salphingo-oophorectomy, bilateral pelvic-paraaortic lymphadenectomy, omentectomy, and intraperitoneal chemotherapy. The uterine corpus revealed three separate masses, which were located at the fundus, anterior and posterior wall. Each tumor revealed three pathologically different components, which were malignant mixed müllerian tumor, papillary serous carcinoma, and endometrioid adenocarcinoma. Among these components, only the papillary serous carcinoma component invaded the underlying myometrium and metastasized to the regional lymph node. Adjuvant chemotherapy and radiation therapy were performed. The patient is still alive and has been healthy for the last 8 yr. We have reviewed previously reported cases of collision tumors which have occurred in the uterine corpus.

Topics: Aged; Aromatase Inhibitors; Carcinoma, Endometrioid; Chemotherapy, Adjuvant; Cystadenocarcinoma, Papillary; Endometrial Neoplasms; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Letrozole; Lymphatic Metastasis; Mixed Tumor, Mullerian; Nitriles; Triazoles; Tumor Suppressor Protein p53

Endometrial polyps are rare sites for metastatic breast carcinoma. Such cases have mostly been reported in tamoxifen-related polyps. We report a case of lobular carcinoma with metastasis to an endometrial polyp in a patient with no history of tamoxifen therapy. The histological features of the polyp in our case closely mimicked those of tamoxifen-related polyps, emphasizing the fact that although characteristic-these features are not specific for tamoxifen. This case also reiterates the need for careful evaluation of endometrial polyps, since inconspicuous deposits of lobular carcinoma can easily be missed.

Topics: Aged; Antineoplastic Agents, Hormonal; Biomarkers; Breast Neoplasms; Carcinoma, Lobular; Endometrial Neoplasms; Female; Humans; Keratins; Polyps; Tamoxifen

Sixteen cases of small-cell carcinoma of the endometrium were encountered in patients who ranged in age from 30 to 78 (mean, 57.4) years. Of the 12 patients whose presenting features are known, eight had abnormal vaginal bleeding, three had pain related to metastatic tumor, and one patient had both symptoms. On pelvic examination, adnexal masses were palpable in three patients, and vaginal involvement was evident in two; one patient had a large palpable periumbilical mass. Thirteen patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Extrauterine spread was documented intraoperatively in eight cases, including widespread intraabdominal and ovarian metastases in four cases, vaginal involvement in the two cases noted previously, paraaortic lymph node involvement in one case, and tubal involvement in one case. Three tumors were International Federation of Gynecology and Obstetrics (FIGO) stage I, four were stage II, two were stage III, and six were stage IV; in one case, there was insufficient information to allow staging. On gross examination, the tumors were usually described as bulky, ill-defined, and invasive of the myometrium; four were polypoid. Microscopic examination revealed sheets, cords, and nests of small or intermediate-sized cells with scanty cytoplasm, hyperchromatic nuclei, and a high mitotic rate. Single-cell and zonal necrosis and vascular invasion were typically present. Synchronous grade 1 or grade 2 endometrial endometrioid adenocarcinoma was present in eight cases, and complex atypical endometrial hyperplasia, in two others. In three cases, the adenocarcinoma merged almost imperceptibly with the small-cell component. None of the tumors contained argyrophil or argentaffin cells, although nine of 11 tumors were immunoreactive for neuron-specific enolase (one of these was also Leu-7 positive), and another was chromogranin positive. Of the 11 cases with follow-up information, seven patients died of disease (at least four with distant metastases) with a median survival of 12 months, and another patient was alive with distant metastases at 18 months. The remaining patients were clinically free of disease at postoperative intervals of < or = 1 year (two cases) and 4.5 years (one case). This study confirms that small-cell carcinomas of the endometrium are a histologically distinctive subtype of endometrial carcinoma, which, like their counterparts in the uterine cervix, are aggressive tumors with a propensity for

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Small Cell; Endometrial Neoplasms; Female; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Neoplasms, Multiple Primary; Phosphopyruvate Hydratase

Sentinel lymph nodes are widely accepted in the treatment of endometrial carcinoma. Whereas surgical aspects are well studied, the pathological work-up in terms of grossing, frozen section, and the so-called ultra-staging is still a matter of debate. This results in conflicting national or center-based recommendations. In a series of consecutive 833 sentinel lymph nodes from 206 patients in endometrial carcinomas, we compared three different grossing techniques and the use of frozen section in terms of anatomy, detection rates, and survival. In total, 42 macro-metastases, 6 micro-metastases, and 25 nodes with isolated tumor cells were found. Lymph nodes affected at least with micro-metastasis were about 0.5cm enlarged. Detection rates in lamellation technique increased with a step of 5.9% to 8.3% in comparison to bi-valved or complete embedding. The lamellation technique presented with a slight beneficial prognosis in pN0 subgroup (OS, p=0.05), which besides size effects might be attributed to trimming loss. In frozen section, this effect was less pronounced than expected (OS, p=0.56). Ultra-staging only revealed additional micro-metastases and isolated tumor cells. Exclusively, macro-metastases showed poor survival (p<0.001). In multivariate analysis, T-stage, subtype, and lympho-vascular invasion status outperformed this staging parameter significantly. Grossing of sentinel lymph nodes is the most essential step with evidence to prefer lamellation in 2 mm steps. Step sectioning should consider widely spaced protocols to exclude macro-metastases. Frozen sections might add value to the intra-operative assessment of endometrial carcinoma in selected cases. The excellent biological behavior of cases with isolated tumor cells might question the routine application of pan-cytokeratin as ultra-staging method.

Topics: Carcinoma; Endometrial Neoplasms; Female; Frozen Sections; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Staging; Sentinel Lymph Node; Sentinel Lymph Node Biopsy

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

Sentinel lymph node biopsy is gaining increasing acceptance as a less morbid way to assess lymph node status in patients with endometrial carcinoma, compared with full pelvic node dissection. The sentinel nodes are usually subjected to ultrastaging, with sections taken at multiple levels from each block and immunstaining for keratin performed, in order to detect micrometastses. We report a case of an 80-yr-old woman who underwent a right sentinel lymph node biopsy at the time of surgery for clinically and radiologically apparent stage I endometrial endometrioid adenocarcinoma. The immunostains for AE1/AE3 performed on the 2 right pelvic sentinel lymph nodes were positive, corresponding to subcapsular acellular keratin on hematoxylin and eosin; however, carcinoma cells could not be identified on the hematoxylin and eosin-stained slides. Immunomarkers for Ber-EP4 and EMA, both of which were strongly expressed in the endometrial carcinoma cells, were negative on the nodal tissue, and we concluded that the sentinel lymph nodes were negative for metastatic carcinoma, despite the positive keratin immunostains. To our knowledge, this unusual finding is not described in the literature; recognition of this phenomenon and study of additional cases is warranted.

Topics: Aged, 80 and over; Carcinoma, Endometrioid; Carcinoma, Squamous Cell; Cell Differentiation; Endometrial Neoplasms; Endometrium; Female; Humans; Hysterectomy, Vaginal; Keratins; Salpingo-oophorectomy; Sentinel Lymph Node; Sentinel Lymph Node Biopsy

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear β-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for β-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the β-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation.

Topics: beta Catenin; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Cell Differentiation; Craniopharyngioma; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Odontogenesis; Pilomatrixoma; Pituitary Neoplasms

The microcystic, elongated, and fragmented (MELF) pattern of myoinvasion in endometrial carcinoma (EC) is associated with an increased risk of lymph node metastasis. Our aim is to assess the role of cytokeratin immunohistochemical (IHC) stains in detecting sentinel nodal metastasis in MELF pattern tumors.. We recovered 19 MELF pattern EC hysterectomies with lymphadenectomy from our files. Negative nodes were subjected to cytokeratin AE1/AE3 IHC. Ten additional cases with sentinel lymph node (SLN) biopsies primarily assessed by IHC were also analyzed.. Of the 19 cases of EC, 6 had positive lymph nodes based on H&E-stained sections at the time of their initial diagnosis. With the addition of IHC stains, 8 previously negative cases were found to have node metastases, and 3 of these were SLNs. Among the 10 cases primarily assessed by IHC, 5 had malignant cells in their SLNs.. Cytokeratin IHC staining detected malignant cells in 9 of 16 cases with SLNs in our sample of women with MELF pattern of myoinvasion. Immunohistochemical stains should be routinely performed on SLNs from all MELF-positive cases to detect occult lymph node metastases and isolated tumor cells.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Retrospective Studies; Sentinel Lymph Node; Sentinel Lymph Node Biopsy

Dedifferentiated endometrioid carcinoma or dedifferentiated endometrioid adenocarcinoma (DEAC) is defined by the presence of undifferentiated carcinoma with endometrioid carcinoma. Undifferentiated component can be misinterpreted as solid component of high-grade endometrioid carcinoma or sarcomatous component of malignant mixed mullerian tumor. We present two cases of DEAC. Two postmenopausal women underwent hysterectomy for vaginal bleeding. Microscopically, sections from the endometrial tumors showed a biphasic growth consisting of an undifferentiated component and a glandular component with sharp transition between the two components. The undifferentiated component showed focal positivity for cytokeratin and vimentin, while glandular component was diffusely positive for cytokeratin and negative for vimentin expression.

Topics: Biomarkers, Tumor; Carcinoma, Endometrioid; Cell Dedifferentiation; Endometrial Neoplasms; Endometrium; Female; Humans; Keratins; Middle Aged; Postmenopause; Prognosis; Ultrasonography; Uterine Hemorrhage

Endometrial stromal sarcomas (ESS) are rare and understudied gynecologic mesenchymal neoplasms. These tumors can be confused with many other gynecologic and nongynecologic tumors due to their variegated morphologic appearance and nonspecific immunohistochemical profile. ESS can express cytokeratin (CK) and, therefore, may be misdiagnosed as carcinoma especially in extrauterine locations and when recurrence/metastasis is present. In this study, we investigated the expression of a wide spectrum of CKs consisting of AE1/3, CAM 5.2, HMCK, MNF116, CK5, CK6, CK7, CK8/18, CK14, CK17, CK19, and CK20 in 6 low-grade and 5 high-grade ESS. In addition, staining for estrogen receptor, progesterone receptor, CD10, and cyclin D1 was performed. Our results showed that CKs AE1/3, CAM 5.2, MNF116, and CK8/18 are more expressed in low-grade ESS, whereas high-grade ESS express more AE1/3 and CAM 5.2. In problematic cases, especially in recurrences or metastases, the immunohistochemical panel of antibodies AE1/3, MNF116, CAM 5.2, and CK8/18, together with other classic immunohistochemical markers CD10, cyclin D1, estrogen receptor, and progesterone receptor, may be helpful in the differential diagnosis between ESS and other gynecologic and nongynecologic malignancies.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cyclin D1; Diagnosis, Differential; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Middle Aged; Neprilysin; Receptors, Estrogen; Receptors, Progesterone; Sarcoma, Endometrial Stromal

Peritoneal keratin granulomatosis is a rare tumor-like lesion caused by deposition of tumor-produced keratin. It may be associated with endometrial or ovarian endometrioid adenocarcinoma, atypical polypoid adenomyoma of the endometrium, or ruptured mature teratomas of the ovary. We present 2 cases of peritoneal keratin granulomatosis associated with FIGO (International Federation of Gynecology and Obstetrics) stage 1 endometrial adenocarcinoma. This entity can mimic advanced-stage disease clinically and radiologically, as it did in those cases, and constitutes a diagnostic pitfall that pathologists and surgeons must be aware.

Topics: Aged; Biopsy; Carcinoma, Endometrioid; Diagnosis, Differential; Endometrial Neoplasms; Endometrium; Female; Granuloma; Humans; Hysterectomy; Keratins; Peritoneal Diseases; Peritoneum; Salpingo-oophorectomy

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

Topics: Biomarkers, Tumor; Endometrial Neoplasms; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Middle Aged; Pain; Positron-Emission Tomography; Radiography, Abdominal; Receptors, Estrogen; Receptors, Progesterone; Tomography, X-Ray Computed; Ultrasonography; Vimentin

Endometrial cancer (EC) is one of the most frequent causes of cancer death among women in developed countries. Histopathological diagnosis and imaging techniques for EC are limited, thus new prognostic markers are needed to offer patients the best treatment and follow-up.In the present paper we showed that the level of mitochondrial ribosomal protein MRPS18-2 (S18-2) increased in EC compared with the normal endometrium and hyperplasia, based on a study of 42 patient biopsies. Importantly, high expression of free E2F1 in EC correlates well with high S18-2 expression. The EC cell line HEC-1-A, which overexpresses S18-2 constitutively, showed an increased proliferation capacity in vitro and in vivo (in SCID mice). Moreover, pan-keratin, beta-catenin and E-cadherin signals are diminished in these cells, compared to the parental HEC-1-A line, in contrast to vimentin signal that is increased. This may be associated with epithelial-mesenchymal cell transition (EMT).We conclude that high expression of S18-2 and free E2F1, and low pan-keratin, beta-catenin, and E-cadherin signals might be a good set of prognostic markers for EC.

Topics: Adenocarcinoma; Animals; Antigens, CD; beta Catenin; Biomarkers, Tumor; Cadherins; E2F1 Transcription Factor; Endometrial Neoplasms; Female; Heterografts; Humans; Keratins; Mice; Mice, SCID; Ribosomal Proteins

Epithelial-mesenchymal transition (EMT) is a critical process for cancer metastasis and recurrence. Metformin, an effective oral antidiabetic drug, has been associated with decreased cancer risk and mortality. In this pilot study, we started to evaluate the effect of metformin on EMT in vivo and in vitro in endometrial cancer (EC).. Endometrial cancer cell lines and freshly isolated EC tumor specimens were used to assess EMT after metformin treatment. Cell lines were subjected to wound healing and AlamarBlue assays to determine cell migration and cell proliferation; messenger RNA levels were measured by real-time reverse transcriptase (RT) quantitative polymerase chain reaction (PCR), and protein levels were measured by Western blots to detect EMT marker expression.. Protein expression and messenger RNA of E-cadherin was found to be increased (P = 0.02 and 0.04, respectively) in 30 EC tumor specimens of diabetic patients treated with metformin compared with 20 EC tumor specimens of diabetic patients treated with other antidiabetic agents. In vitro, metformin reduced cell migration at 5 mM for 48 hours, as determined by the wound healing assay in EC cell lines (Ishikawa, 45% reduction; HEC50, 40% reduction), whereas more than 90% of the cells remained viable on the AlamarBlue assay. Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.. Tumors of patients on metformin have increased E-cadherin expression, and metformin decreases EMT in EC cell lines in vitro, suggesting clinical biological relevance of metformin in women with EC.

Topics: Adult; Aged; Aged, 80 and over; Cadherins; Carcinoma; Cell Line, Tumor; Cell Movement; Diabetes Mellitus, Type 2; Drug Screening Assays, Antitumor; Endometrial Neoplasms; Epithelial-Mesenchymal Transition; Female; Humans; Hypoglycemic Agents; Keratins; Metformin; Middle Aged; Pilot Projects; Retrospective Studies

Topics: Biomarkers, Tumor; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mismatch Repair Endonuclease PMS2; MutL Protein Homolog 1

Well-characterized, low-passage, primary cell cultures established directly from patient tumors are an important tool for drug screening because these cultures faithfully recapitulate the genomic features of primary tumors. Here, we aimed to establish these cell cultures from primary endometrial carcinomas (ECs) and to develop subcutaneous and orthotopic xenograft models as a model to validate promising treatment options for EC in the in vivo setting.. Primary cell cultures of EC tumors were established and validated by analysing histologic and genetic characteristics, telomerase activity, and in vitro and in vivo growth characteristics. Using these primary cell cultures, subcutaneous and orthotopic mouse models were subsequently established.. We established and characterized 7 primary EC cell cultures and corresponding xenograft models of different types of endometrioid tumors. Interestingly, we observed that the chance to successfully establish a primary cell culture seems higher for microsatellite instable than microsatellite stable tumors. For the first time, we also established an orthotopic murine model for EC derived from a primary cell culture. In contrast to EC cell lines, grafted tumor cultures preserved the original tumor structure and mimicked all histologic features. They also established abdominal and distant metastases, reflecting the tumorigenic behavior in the clinical setting. Remarkably, the established cell cultures and xenograft tumors also preserved the genetic characteristics of the primary tumor.. The established EC cultures reflect the epithelial genetic characteristics of the primary tumor. Therefore, they provide an appropriate model to investigate EC biology and apply high-throughput drug screening experiments. In addition, the established murine xenograft models, in particular the orthotopic model, will be useful to validate promising therapeutic strategies in vivo, as the grafted tumors closely resemble the primary tumors from which they were derived. Microsatellite instable status seems to determine the success rate of establishing primary cell cultures.

Topics: Adult; Aged; Animals; Carcinoma; Cell Proliferation; Disease Models, Animal; Endometrial Neoplasms; Female; Humans; Keratins; Mice; Mice, Nude; Microsatellite Instability; Microsatellite Repeats; Middle Aged; Neoplasm Transplantation; Primary Cell Culture; Receptors, Estrogen; Receptors, Progesterone; Tumor Cells, Cultured; Vimentin

Proper evaluation of lung nodules is a difficult issue for clinical management of patients. Discriminating metastatic endometrial stromal sarcoma (ESS) from other primary spindle cell neoplasms of the lung using histological analysis can be challenging. This is particularly true when an adequate clinical history is lacking, because ESS metastasis can be delayed by a couple of decades. To emphasize the importance of the correlation of pathological findings with clinical history and imaging studies, we investigated 11 cases of ESS (seven low grade and four high grade) metastatic to the lung. All cases presented with one to multiple unilateral or bilateral lung nodules that were detected by chest computed tomography. Primary ESS was diagnosed from hysterectomy specimens except for one by endometrial biopsy, 0.5 to 23 years prior to metastasis. Immunohistochemical studies showed that all ESS cases were moderately to strongly positive for Bcl-2 and CD10 with >50% of tumor cells stained, except for one high grade ESS that was negative for CD10. Eight (72.7%) and seven (63.6) of the 11 cases showed positive estrogen and progesterone receptors, respectively, with a majority of positive cases showing diffuse and moderate to strong staining. Strong but patchy staining for CD34 was detected in one (9.1%) case with smooth muscle differentiation. CK7 and TTF-1 were negative in all cases. Two (18.2%) cases exhibited patchy and strong positivity for caldesmon. Two (18.2%) low grade ESS cases showed moderate to strong AE1/AE3 positivity in >50% of tumor cells, one of which also showed moderate CK19 and Cam 5.2 staining in >30% of tumor cells. One should be cautious when assessing spindle cell neoplasms of the lung in women with a history of hysterectomy. Correlation of clinical history and imaging studies with histological and immunohistochemical findings is essential to diagnosis of metastatic ESS to the lung.

Topics: Aged; Biomarkers, Tumor; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Middle Aged; Neprilysin; Proto-Oncogene Proteins c-bcl-2; Radiography; Sarcoma, Endometrial Stromal; Staining and Labeling

We present a 69-year-old woman with a chief complaint of postmenopausal bleeding. She was diagnosed as having an endometrioid adenocarcinoma by biopsy, and underwent a total abdominal hysterectomy. At the time of surgery, granulation tissue-like nodules were found on the peritoneal serosa of the uterus. In the intraoperative cytology of peritoneal washing, atypical cells were noted. The intraoperative frozen section of the peritoneal nodule revealed granulation tissue with proliferating mesothelial cells. Microscopic examination of the permanent section showed keratin granulomas without viable adenocarcinoma cells on the serosal surface of the ovaries, fallopian tubes and broad ligaments. Postoperative chemotherapy was administered. She has been alive with no evidence of recurrence for 6 months postoperatively. It should be noted that the prognosis of cases in peritoneal keratin granuloma without viable cancer cells is favorable, and that the histological examination is essential for its diagnosis.

Topics: Aged; Antineoplastic Agents; Carcinoma, Endometrioid; Chemotherapy, Adjuvant; Endometrial Neoplasms; Female; Granuloma; Humans; Hysterectomy; Immunohistochemistry; Keratins; Peritoneal Diseases

Canine endometrial carcinomas are rare, and mostly occur in geriatric bitches. In this work, the uterus of a 10-year-old female Boxer evidencing an endometrial carcinoma on the body of the uterus was used to describe the histopathological features of the tumour and to study its immunophenotype. In this work, a panel of immunomarkers (cytokeratins AE1/AE3 and 14, vimentin, CD10 and Ki-67) was applied to the endometrial carcinoma to establish the staining patterns indicative of the tumour agressiveness and cellular differentiation. Additionally DNA ploidy was also performed. In this case, the tumour showed papillar pattern, with large pleomorphic, anaplastic cells and also some aberrant multinucleated and giant cells. In some areas of the tumour, it was also observed cytotrophoblastic-like cells outlining the papillae. Cytokeratin AE1/AE3 expression was detected in the luminal neoplasic cells. Cytokeratin 14 positivity was sporadic and irregular, and was observed mainly in the luminal epithelium. Only stromal and aberrant cells showed a positive staining to vimentin. Positive membranous staining to CD10 was evidenced by clear epithelial, cytotrophoblastic-like cells at the tumour surface but not by the stromal cells. The mitotic and Ki-67 indices were low, suggestive of a weak aggressiveness of the tumour. The multinucleated and giant cells evidenced a positive immunostaining to CK AE1/AE3, and CD 10; its positivity to vimentin was sporadic. This study aims to contribute to the advancement of the knowledge in canine endometrial carcinoma immunophenotype.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; Dog Diseases; Dogs; Endometrial Neoplasms; Female; Immunohistochemistry; Keratins; Ki-67 Antigen; Neprilysin; Vimentin

Endometrial stromal sarcomas can be confused with several neoplasms because of their inconsistent and widely varied morphologic appearance and frequent immunohistochemical expression of a variety of antigens including cytokeratin. The resulting diagnostic challenge becomes problematic particularly in the diagnosis of metastases resulting from such tumors. Because of the sometime epithelioid appearance of the tumor cells and their expression of cytokeratin, the metastases may be misdiagnosed as poorly differentiated carcinoma. We therefore studied the profile of cytokeratin proteins expression in 17 cases of endometrial stromal sarcomas using a panel of antibodies including cytokeratin cocktail antibody (AE1/AE 3), CK5/6, CK7, CK14, CK16, Cam5.2 (CK8), CK19, CK20, and 34Ebeta12 (CK1, 5, 10, and 14). Of the 17 cases, 8 (47%) stained positive with the cytokeratin cocktail antibody (AE1/AE 3). Of the 8 cases with cytokeratin expression, 5 (63%) stained positive with CK19, and 3 of them stained positive with Cam5.2. The 3 cases that stained positive with Cam5.2 also expressed CK19. Of the 5 cases with CK19, 1 was focally positive for CK5/6, CK7, and 34Ebeta12. None of the cases expressed CK14, CK16, or CK20. These results show that CK19 is most commonly expressed cytokeratin in endometrial stromal tumors. Hence, the inclusion of CK19 in the panel of immunostains may help resolve the diagnostic confusion created by keratin expression in endometrial stromal sarcoma and may also help in the correct diagnosis of endometrial stromal sarcoma at extrauterine sites.

Topics: Adenocarcinoma; Biomarkers, Tumor; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratin-19; Keratins; Neoplasm Metastasis; Sarcoma, Endometrial Stromal; Tissue Array Analysis

p63 and cytokeratin (CK) 5/6 are markers of basal and squamous differentiation in several normal epithelia and human tumors and are also suggested to be markers of progenitor or stem cells in certain stratified epithelia. In endometrial carcinoma, there is very limited information about the expression pattern of p63 or CK5/6 and no prognostic information. The aim of our study was to examine whether the expression of these markers was associated with a certain tumor phenotype in terms of other biomarkers, clinicopathologic characteristics and patient prognosis. Immunohistochemical expression of p63 and CK5/6 was examined using tissue microarrays (TMAs) in a large population-based series of 276 endometrial carcinomas with long and complete follow-up. Selected cases of normal and hyperplastic endometrium were examined for comparison (n = 15). Absence of p63 expression (70%) was significantly associated with nonendometrioid carcinomas, high histologic grade (FIGO), higher mitotic count and tumor cell proliferation by Ki-67, microsatellite instability (MSI) and loss of hMSH6 expression. A tendency toward reduced patient survival was also seen (p = 0.098). Presence of CK5/6 expression was more frequent in endometrioid tumors with squamous differentiation, while loss of CK5/6 expression (54%) was significantly associated with high FIGO stage, reduced beta-catenin expression, MSI and reduced patient survival (p = 0.0001); the latter was also found within the endometrioid subgroup (p = 0.0004). Multivariate survival analysis revealed that loss of CK5/6 expression had an independent prognostic impact in addition to well-known prognostic variables. Expression of both markers was increased in simple hyperplasia compared with normal endometrium. In complex hyperplasia, p63 expression was also increased, whereas CK5/6 was positive in areas with squamous differentiation only. Thus, loss of p63 or CK5/6 was associated with features of aggressive tumors, and lack of CK5/6 was significantly associated with reduced survival in multivariate analysis.

Topics: Biomarkers, Tumor; DNA-Binding Proteins; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Keratins; Phosphoproteins; Survival Rate; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Some endometrial cancer patients without clinical evidence of extrauterine spread die as a result of recurrence even after curative operation. These recurrences may arise from occult tumor cells that are not detected by conventional methods. The goal of this study was to develop a quantitative method for the detection of disseminated tumor cells (DTCs) in the peripheral blood (PB) and lymph nodes (LNs) of patients with endometrial cancer.. Ninety-eight PB samples from 30 patients and 218 LNs from 14 patients were studied. Real-time quantitative analysis was performed using a LightCycler instrument and a TaqMan probe for cytokeratin 19 (CK19) as a marker gene.. This method resulted in the reproducible quantitation of 10 to 10(6) MCF-7 cells (CK19-expressing breast cancer cell line) per 10(6) peripheral blood nucleated cells. CK19 mRNA expression was detected in 28 PB samples and in 62 LNs. Only three preoperative PB samples and one postoperative PB sample (from four patients) and 33 LNs (from six patients) were PCR-positive. The PCR-positive rate of LNs was higher in patients with pathologically metastatic (path-positive) LNs than in patients with path-negative but PCR-positive LNs. Furthermore, the CK19 mRNA background expression rate was higher in the LNs of path-negative but PCR-positive patients than in LNs of path-negative and PCR-negative patients.. Real-time qRT-PCR with TaqMan probes is a sensitive, specific and rapid method for the detection of DTCs in PB and LNs. Additional studies with larger numbers of patients and adequate follow-up would be of benefit.

Topics: Aged; Cell Line, Tumor; Endometrial Neoplasms; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Ribosomal, 18S

To study alterations within the p53 pathway in relation to the development of recurrent stage I endometrioid endometrial carcinoma.. Paraffin-embedded tumor tissue of both primary and recurrent tumors from 44 patients with and 44 without recurrence was used for immunohistochemical analysis of TP53, hMdm2, P21(Waf1/Cip1) and M30. DNA was extracted, and mutation analysis of p53 (exon 5-8, 11) was performed by direct sequencing.. TP53 overexpression was significantly associated with recurrent disease: Odds Ratio 3.8 (95% CI: 1.5-9.8). Overexpression of TP53 was associated with lower staining indices (SI:0-9) of both hMdm2 and P21 in tumors of patients with recurrence, compared to controls: 2.0 +/- 0.4 vs. 4.0 +/- 0.8 and 1.9 +/- 0.8 vs. 3.6 +/- 0.8, respectively. Eight p53 missense mutations were identified in six patients with recurrence and two controls. One nonsense mutation was found in a patient with recurrence and one deletion in a control patient. Only a minority of TP53 overexpression cases could be explained by the presence of these p53 mutations.. TP53 overexpression was significantly predictive for recurrent endometrial carcinoma, and mostly not correlated with p53 mutations. Concomitant low hMdm2 and P21(Waf1/Cip1) expression in tumors with overexpressed TP53 suggests a dysfunctional TP53-P21(Waf1/Cip1) pathway.

Topics: Aged; Aged, 80 and over; Apoptosis; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mutation; Neoplasm Recurrence, Local; Paraffin Embedding; Proto-Oncogene Proteins c-mdm2; Tumor Suppressor Protein p53

This is the first report of breast carcinoma metastatic to the endometrium in a patient on adjuvant anastrozole therapy. We report a case of metastatic lobular carcinoma of the breast in a 63-year-old patient on adjuvant anastrozole therapy for 8 months. She was asymptomatic and metastatic endometrium was diagnosed after transvaginal ultrasound revealed suspicious findings along with elevated Ca 15-3 levels. As further work up showed no other metastatic sites her uterus was taken out along with her ovaries and pelvic lymph nodes. Uterine metastases should be kept in mind in asymptomatic patients on anastrozole therapy.

Topics: Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chemotherapy, Adjuvant; Endometrial Neoplasms; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Mastectomy, Modified Radical; Middle Aged; Mucin-1; Nitriles; Ovariectomy; Triazoles; Ultrasonography; Vagina

Endometrial cancer cell lines have provided a valuable model to study endometrial epithelial cells in vitro. Since the first development of HEC1B over 35 yr ago, many different cell lines have been isolated and described. One valuable cell line that maintains hormone responsiveness and unique stability over time is the ECC-1 cell line, developed originally by the late P.G. Satyaswaroop. In this study, we investigated some of the properties of these cells and present their salient characteristics. Like Ishikawa cells, ECC-1 cells maintain both estrogen receptors (ESR1 [ER alpha] and ESR2 [ER beta]), progesterone receptors (PR A and B; PGRs), and androgen receptors (ARs), along with the p160 steroid receptor coactivators NCOA1 (formerly SRC1), NCOA2 (formerly TIF2), and NCOA3 (formerly AIB1). The karyotype of these cells is abnormal, with multiple structural rearrangements in all cells analyzed. Unlike Ishikawa cells that express glandular epithelial antigens, ECC-1 cells maintain a luminal phenotype, with expression of KRT13 (cytokeratin 13) and KRT18 (cytokeratin 18). Apparent differences in the regulation of ESR2 also were evident in ECC-1 cells compared to Ishikawa cells. Like other endometrial cell lines, ECC-1 cells express the steroid receptor coactivators and exhibit epidermal growth factor-stimulated expression of known luminal proteins thought to be involved in implantation, including the hyaluronate receptor CD44 and SPP1 (formerly osteopontin) and CD55 (decay-accelerating factor). These characteristics appear to be stable and persistent over multiple cell passages, making this well-differentiated cell line an excellent choice to study endocrine and paracrine regulation of endometrial epithelium in vitro.

Topics: Binding, Competitive; Blotting, Western; Cell Line, Tumor; Endometrial Neoplasms; Endometrium; Epithelial Cells; Epithelium; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Humans; Immunohistochemistry; Karyotyping; Keratins; Phenotype; Protein Binding; Receptors, Androgen; Receptors, Progesterone; Reverse Transcriptase Polymerase Chain Reaction; Steroids

We report a case of monostotic low-grade stromal sarcoma (ESS) with sex cord-like elements metastatic to the thoracic spines, which to the best of our knowledge has not previously been documented. A 48-year-old female who had undergone total abdominal hysterectomy for low-grade endometrial stromal sarcoma 7 years previously presented with insidious onset of severe back pain of 2 months' duration. Magnetic resonance image (MRI) showed involvement of the eleventh and twelfth thoracic vertebral bodies. Decompression at the level of T10-12 was performed. Histologically, the laminae of thoracic vertebrae 11 and 12 were replaced by sheets of ovoid cells with plump nuclei intermixed with anastomosing trabeculae, cords and small nests, reminiscent of a sex-cord stromal tumor pattern. The tumor cells showed diffuse nuclear immunostaining for estrogen receptors (ER) and progesterone receptors (PR), as well as membranous immunostaining for CD10. The immunostaining for smooth muscle actin was focal and sparse. These findings confirmed the diagnosis of metastatic low-grade ESS with sex cord-like differentiation. Low-grade ESS with sex cord-like differentiation is an uncommon tumor which rarely metastasizes to the bone, and use of a panel of ER, PR, CD10, actin, cytokeratin and inhibin immunostains is essential to establish the diagnosis.

Topics: Actins; Endometrial Neoplasms; Female; Humans; Hysterectomy; Keratins; Magnetic Resonance Imaging; Middle Aged; Neprilysin; Receptors, Estrogen; Receptors, Progesterone; Sarcoma, Endometrial Stromal; Sex Cord-Gonadal Stromal Tumors; Spinal Neoplasms; Thoracic Vertebrae

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Carcinoma, Signet Ring Cell; Diagnosis, Differential; Diagnostic Errors; Endometrial Neoplasms; Endometrium; Female; Humans; Keratins

Endometrial stromal sarcomas are low-grade malignant tumors that may pose a diagnostic challenge, especially when they are present in an extrauterine site. Owing to the presence of an arborizing vasculature and cells with an undifferentiated appearance, endometrial stromal sarcomas can be confused with several soft-tissue neoplasms. We studied 17 endometrial stromal sarcomas, eight hemangiopericytomas, 14 solitary fibrous tumors, and 16 synovial sarcomas immunohistochemically, detecting the following antigens: CD10, estrogen receptor, progesterone receptor, bcl-2, CD34, smooth muscle antigen, epithelial membrane antigen and cytokeratin (AE1/AE3). Most endometrial stromal sarcomas stained positively for CD10 (16/17), estrogen receptor (17/17), progesterone receptor (15/17), and bcl-2 (17/17). Staining with antismooth muscle antigen was seen in 11 of 17 cases of endometrial stromal sarcoma, with more intense staining seen in areas showing smooth muscle differentiation. Staining with AE1/3 was seen in four of 17 endometrial stromal sarcomas, with two of the positive cases containing epithelioid cells. None of the endometrial stromal sarcomas expressed epithelial membrane antigen or CD34. More than half of the hemangiopericytomas (4/8) and solitary fibrous tumors (9/14) cases demonstrated CD10 expression either focally or in a patchy cytoplasmic and membranous pattern. Hemangiopericytomas, solitary fibrous tumors, and synovial sarcomas did not express estrogen receptor. Four of eight hemangiopericytomas and seven of 14 solitary fibrous tumors also showed patchy progesterone receptor expression. CD34 expression was identified in six of eight hemangiopericytomas and 13 of 14 solitary fibrous tumors, but we did not find expression of CD34 in synovial sarcoma. Differences between endometrial stromal sarcoma and other soft-tissue tumors were detected for all of the immunohistochemical markers (P<0.05), except anti-bcl-2 and AE1/3. Antibodies against CD10 mark a substantial number of hemangiopericytomas and solitary fibrous tumors (albeit not diffusely) and should always be combined with antiestrogen receptor and CD34 when the differential diagnosis includes endometrial stromal sarcoma. Unlike estrogen receptor antibodies, progesterone receptor antibodies show at least focal nuclear staining in most hemangiopericytomas, solitary fibrous tumors and rare synovial sarcomas, and are not useful for this differential diagnosis. All endometrial stromal sarcomas expressed

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD34; Biomarkers, Tumor; Chi-Square Distribution; Diagnosis, Differential; Endometrial Neoplasms; Female; Hemangiopericytoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Neprilysin; Proto-Oncogene Proteins c-bcl-2; Receptors, Progesterone; Sarcoma, Endometrial Stromal

Lymph-vascular space invasion has been established as an independent prognostic factor in endometrial adenocarcinoma. Despite the importance of its recognition, the histologic patterns of lymph-vascular space involvement have not been well addressed in the surgical pathology literature. We report three cases of endometrioid adenocarcinoma of the uterine corpus associated with a subtle pattern of lymph-vascular space invasion closely mimicking intravascular histiocytes. Two cases had regional lymph node metastases composed of morphologically similar cells.

Topics: Aged; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Histiocytes; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Treatment Outcome

Squamous metaplasia of endometrium is mostly manifested by morules or nodules of benign nonkeratinizing squamous cells intimately mixed with benign or malignant endometrial glands. It has been described with low-grade adenocarcinoma of the endometrium, as well as with various benign conditions, including hyperplasia, chronic endometritis, and endometrial polyps. However, extensive plaquelike, keratinizing squamous change is distinctly uncommon. To our knowledge, we describe the first case of extensive benign squamous keratinization with underlying endometrial adenocarcinoma.

Topics: Adenocarcinoma; Aged; Endometrial Neoplasms; Female; Gynecologic Surgical Procedures; Humans; Ichthyosis; Keratins; Uterus

Lymphovascular Invasion (LVSI) of tumour cells is marked as an important step in the process of tumour metastases and is an important prognostic factor in Endometrial Cancer (EC). Currently, the standard method for assessing LVSI is light microscopic examination of H&E stained sections. Tumour cells within lymphovascular spaces can evade detection on H&E staining if they are present in very small numbers or surrounded by a greater number of circulating cells. Dual immunostaining for epithelial and endothelial cell markers cell markers has been shown to increase detection rate of LVSI significantly.. To investigate the clinical significance of LVSI as detected by H&E (LVSI-H&E) and immunohistochemically (LVSI-IHC) in clinically stage I endometrioid EC patients. Methods. Single representative section of 90 patients with stage I endometriod EC were immunostained in accordance with established streptavidin-biotin peroxidase method using a mouse monoclonal pancytokeratin (PCK), clone AE1/AE3 and CD31 endothelial cell marker. The H&E sections and their corresponding immunostained sections were re-examined to identify LVSI. Clinical records were available on 72 patients. The following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes and hypertension), use of Tamoxifen or HRT, menopausal state, recurrence and survival.. Overall, LVSI was present in 45 (50%) cases and absent in 45 (50%) cases on IHC, as compared with 17 (19%) and 73 (81%) cases, respectively, on H&E. Statistical analysis revealed significant association between LVSI-H&E and depth of myometrial invasion (P < 0.0001). The median follow-up period was 161 months (range 5-207 months). During the follow-up period, six of 14 cases with evidence of LVSI-H&E presented with recurrence as opposed to six of 58 patients with no evidence (OR = 6.26, 95%: CI = 1.3-30.6). There was a significant association between tumour recurrence rate and LVSI-H&E (P = 0.01). The 5-year recurrence-free survival was 54% for the group with H&E evidence of LVSI (95%: CI = 44-64%) compared with 89% for the group without (95%: CI = 82-97%). There was a significant difference in the recurrence-free survival between the two groups (Chi-square = 6.96, P = 0.008). In contrast, LVSI-IHC was found to be significantly associated only with high-grade tumours (P = 0.01) and survival analysis revealed no statistically significant association with recurrence or survival.. LVSI-H&E in stage I EC remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event, associated with tumour grade and appears to be of no statistically significant clinical value.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Endometrioid; Endometrial Neoplasms; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymphatic Vessels; Middle Aged; Neoplasm Staging

Tamoxifen is the primary hormonal therapy for breast cancer and is also used as a breast cancer chemopreventative agent. A major problem with tamoxifen therapy is undesirable endometrial proliferation. To identify proteins associated with the growth stimulatory effects of tamoxifen in an ER-positive model, the present study profiled total cellular and secreted proteins regulated by estradiol and selective estrogen receptor modifiers (SERMs) in the Ishikawa endometrial adenocarcinoma cell line using two-dimensional gel electrophoresis. Following 24 h incubation with 10(-8) M estradiol, 10(-7) M 4-hydroxytamoxifen, or 10(-7) M EM-652 (Acolbifene), nine proteins exhibited significant increase in expression. The proteins identified were heat shock protein 90-alpha, and -beta, heterogeneous nuclear ribonucleoprotein F, RNA polymerase II-mediating protein, cytoskeletal keratin 8, cytoskeletal keratin 18, ubiquitin-conjugating enzyme E2-18 kDa and nucleoside diphosphate kinase B. These protein profiles may serve as novel indices of SERM response and may also provide insight into novel mechanisms of SERM-mediated growth.

Topics: Biomarkers; Carrier Proteins; Cell Line, Tumor; Cell Proliferation; Endometrial Neoplasms; Estradiol; Female; Heterogeneous-Nuclear Ribonucleoprotein Group F-H; HSP90 Heat-Shock Proteins; Humans; Keratins; Lactoferrin; Neoplasm Proteins; Phosphoproteins; Piperidines; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Tamoxifen; Ubiquitin-Conjugating Enzymes

To study the roles of cytokeratin (CK) and CA(125) in diagnosing lymph node micrometastasis in endometrial cancer.. The expressions of CK and CA(125) in 50 primary tumors and 298 lymph nodes from 50 patients with endometrial cancers were analysed by immunohistochemical methods.. (1) The positive expression rates of CK and CA(125) in primary tumors of cases with endometrial cancer were respectively 100%, and 78%. (2) The expressions of CK and CA(125) in metastatic lymph nodes were both strong with 100% positive rate. In lymph nodes without metastasis, the expressions of CK and CA(125) were both weak, with positive rates of 15% and 12% respectively. (3) Among patients with stage I, II diseases, tumor recurrence rate was significantly higher in patients with positive CK or CA(125) expression in lymph nodes than in patients without CK or CA(125) expression (P < 0.05). (4) Multiple regression analysis revealed that in stages I, II endometrial cancer, CK expression in lymph nodes, and CA(125) expression in lymph nodes together with depth of myometrial invasion were relevant factors with tumor recurrence.. CK expression in lymph nodes without metastasis can predict lymph node micrometastasis and is an independent risk factor for recurrence of disease in stages I, II endometrial cancers. CA(125) expression in lymph nodes without metastasis can also suggest lymph node micrometastasis, but it is not an independent predictive factor for tumor recurrence in stages I, II endometrial cancers.

Topics: Adult; Aged; Antigens, Neoplasm; CA-125 Antigen; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Pregnancy; Regression Analysis; Risk Factors

Adenocarcinomas of the uterine cervix show a wide range of morphological features, and can be confused with endometrial adenocarcinoma in biopsy or curetting specimens. The objective of this study was to use tissue microarray technology to evaluate the immunoprofile of a large set of uterine adenocarcinomas with an extended panel of antibodies, comparing the profile of primary cervical and endometrial adenocarcinomas. A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 141 hysterectomy specimens. Duplicate 0.6-mm cores were obtained from 57 cervical adenocarcinomas (16 in situ and 41 invasive) and 84 endometrial adenocarcinomas. Tissue array sections were immunostained with 21 commercially available antibodies [B72.3, CD 99, carcinoembryonic antigen (CEA), c-kit, pancytokeratin, CK 5/6, CK 7, CK8/18, CK19, CK 20, CK 22, EMA, estrogen receptor (ER), KP-1, melan-A, p53, PLAP, S-100, synaptophysin, TTF-1, and vimentin] utilizing the avidin-biotin (ABC) technique. Hierarchical clustering analysis of the tumors was done based on the immunostaining results. Only ER ( P<0.001), CEA ( P=0.04), vimentin ( P<0.001), and CK 8/18 ( P=0.002) showed a significantly different frequency of positivity in endometrial relative to cervical adenocarcinomas. ER, vimentin, and CK 8/18 were more likely to be expressed in endometrial adenocarcinomas, while cervical adenocarcinomas more frequently expressed CEA. We were able to identify immunoprofiles that were highly specific for endocervical adenocarcinoma (ER(-), vimentin(-), CK 8/18(-), CEA(+)) or endometrial adenocarcinoma (ER(+), vimentin(+), CK 8/18(+), CEA(-)), but most tumors showed an intermediate, non-specific immunophenotype. Hierarchical clustering analysis was useful in the interpretation of these intermediate immunophenotypes. Papillary serous adenocarcinoma of the endometrium was less likely to express vimentin ( P=0.002) than endometrioid carcinoma of the endometrium.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Receptors, Estrogen; Uterine Cervical Neoplasms; Vimentin

Two cases of lobular breast carcinoma metastatic to an endometrial polyp are described. Both patients had been treated with tamoxifen and presented with abnormal uterine bleeding. Histology of endometrial biopsy in both cases showed typical tamoxifen-associated endometrial polyps with focal subtle stromal infiltration by metastatic lobular breast carcinoma. This was confirmed by positive immunohistochemical staining with cytokeratin epithelial markers. Metastatic breast carcinoma may rarely involve tamoxifen-associated endometrial polyps. Because primary endometrial carcinomas may also arise within tamoxifen polyps, these should be extensively sampled. We briefly review polypoid uterine lesions that may occur secondary to tamoxifen therapy.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma, Lobular; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Polyps; Tamoxifen

Carcinomas with micropapillary features have been described in the breast, urinary bladder, lung, and ovary. They are characterized by the presence of micropapillary tufts in clear spaces. Unequivocal vascular invasion is usually present at the periphery of the tumor. Consequently, these tumors have a high propensity for lymph node metastases and high-stage disease. The metastatic carcinoma can consist exclusively of the micropapillary component, which may elicit an erroneous diagnosis if located in the bladder or lung, as in the patient presented herein. We present a case of a 59-year-old woman with a history of bilateral breast carcinoma status post-bilateral mastectomy, chemotherapy, and tamoxifen therapy. She presented with urinary frequency, and a pelvic mass was noted. A biopsy of the endometrium revealed a poorly differentiated carcinoma. Urinary bladder biopsies showed a carcinoma with micropapillary features diagnosed as micropapillary transitional cell carcinoma. She presented to M.D. Anderson Cancer Center (Houston, TX) for further treatment recommendations. The urinary bladder and endometrial biopsies both contained carcinomas with micropapillary features. The mastectomy specimen showed an invasive ductal carcinoma with a significant micropapillary component. The tumor cells from the breast, endometrium, and urinary bladder were positive for cytokeratin (CK) 7 and estrogen receptor and negative for CK20. In view of the morphologic and immunohistochemical profile, the carcinoma in the endometrium and urinary bladder were interpreted as metastatic lesions from the breast primary. Carcinomas with a micropapillary component are morphologically identical in the breast, urinary bladder, and lung. However, micropapillary serous carcinoma has a different appearance more akin to borderline tumors of the ovary. Immunohistochemical stains are useful in distinguishing these lesions in that thyroid transcription factor-1 positivity suggests a lung primary, CK7 and estrogen receptor suggest a breast primary, and both CK7 and CK20 positivity suggest a urinary bladder primary. It is important to exclude metastatic carcinomas with micropapillary features before making a definite diagnosis of a primary tumor. Carcinomas with micropapillary features have a propensity for lymph node metastases and advanced stage disease. This article discusses the differential diagnosis of carcinomas with micropapillary features in different organs.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Papillary; Carcinoma, Transitional Cell; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lung Neoplasms; Middle Aged; Receptors, Estrogen; Urinary Bladder Neoplasms

A three-dimensional (3-D) endometrium culture was established, in which human endometrial stromal cells embedded in a mixture of collagen I, a major component of extracellular matrix, and matrigel, a basement membrane material, supports the epithelial cells seeded on top of the collagen/matrigel matrix. The biological growth and differentiation of the epithelial cells were studied microscopically and immunohistochemically. Transmission electron microscopy showed a polarized columnar epithelium in monolayer with basally positioned nuclei. Scanning electron microscopy revealed a confluent epithelium with an abundance of microvilli and cilia as well as pinopodes on the apical surface. An immunohistochemical staining showed that integrin alpha1, alpha4, and beta3 were co-localized with cytokeratin, confirming the epithelial origin of the cells. In contrast, immunoreactivity against cyclooxygenase-1 or -2 was positive in both epithelial and stromal cells. When epithelial cells were replaced by KLE cells, an endometrial cancer cell of epithelial origin, invasion of KLE cells into the stromal fraction was observed. The invasion was closely correlated to expression of matrix metalloproteinases and their tissue inhibitors of metalloproteinases in a manner consistent with paracrine fashion. The present 3-D culture imitates the normal endometrium physiologically as well as morphologically, thus provides an excellent in vitro tissue suitable for reproducing in vivo physiological processes, including endometrial cancer invasion.

Topics: Cell Communication; Cell Differentiation; Cells, Cultured; Collagen; Collagen Type I; Culture Media; Culture Techniques; Cyclooxygenase 1; Cyclooxygenase 2; Drug Combinations; Endometrial Neoplasms; Endometrium; Epithelial Cells; Female; Humans; Integrin alpha1; Integrin alpha4; Integrin beta3; Isoenzymes; Keratins; Laminin; Matrix Metalloproteinases; Membrane Proteins; Microscopy, Electron; Microscopy, Electron, Scanning; Neoplasm Invasiveness; Neoplasm Proteins; Prostaglandin-Endoperoxide Synthases; Proteoglycans; Stromal Cells; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

Angiogenesis is critical for the growth and metastasis of endometrial cancer and is therefore an important therapeutic target. Vascular endothelial growth factor-A (VEGF-A) is a key molecule in angiogenesis, but the identification of related molecules and the angiopoietins suggests a more complex picture. We investigated the presence of transcripts for VEGF-A, VEGF-B, VEGF-C, VEGF-D, Angiopoietin-1 and Angiopoietin-2 in benign endometrium, atypical complex hyperplasia (ACH) and endometrioid endometrial carcinoma using in situ hybridisation. We confirmed the presence of VEGF-A mRNA in the epithelial cells of cancers examined (13 out of 13), but not in benign endometrium or ACH. We also demonstrate, using quantitative polymerase chain reaction, that levels of VEGF-B mRNA are significantly lower in endometrial cancer than benign endometrium. We conclude that loss of VEGF-B may contribute to the development of endometrial carcinoma by modulating availability of receptors for VEGF-A.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inducing Agents; Angiopoietin-1; Angiopoietin-2; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Endometrial Hyperplasia; Endometrial Neoplasms; Endothelial Growth Factors; Epithelium; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Intercellular Signaling Peptides and Proteins; Keratins; Lymphokines; Membrane Glycoproteins; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transcription, Genetic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

To assess the correlation between expression of proliferation antigen Ki-67, early apoptotic protein M30 (M30CytoDEATH, CK18) and biologic characteristics in endometrial carcinoma.. SP immunohistochemical technique was used to detect the expression of Ki-67 and M30 in 79 cases of endometrial carcinoma respectively.. The mean Ki-67 indices varied with histological grading and clinical stage of the tumor, being 20.48 +/- 14.86 in grade 1, 24.12 +/- 14.42 in grade 2 and 38.84 +/- 11.88 in grade 3; 20.65 +/- 13.56 in stage I; 26.92 +/- 14.71 in stage II; and: 35.14 +/- 14.70 in stage III. The mean M30 indices varied with the grading and stage of the tumor, being 1.03 +/- 1.42 in grade 1, 1.03 +/- 1.64 in grade 2 and 1.94 +/- 1.20 in grade 3; 0.30 +/- 0.58 in stage I; 1.66 +/- 1.74 in stage II; and 2.07 +/- 1.62 in stage III.. Ki-67 and M30 indexes are significantly correlated with biologic behavior and prognosis in endometrial carcinoma. There is a positive relationship between Ki-67 and M30 indexes.

Topics: Apoptosis; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Neoplasm Staging; Prognosis

Lymphovascular space invasion (LVSI) is an important step in the complex process of tumour metastasis. Various methods have been used in the past to improve the histological detection of LVSI.. To develop a sensitive immunohistochemical method for the detection of LVSI.. Paraffin wax blocks from 108 patients who had undergone hysterectomy for stage I endometrial cancer were retrieved. Dual immunostaining for pancytokeratin and the CD31 endothelial cell marker was carried out on 4 micro m sections cut from these bocks and compared with conventional haematoxylin and eosin staining.. The detection rate for LVSI increased threefold compared with conventional haematoxylin and eosin staining in the test group.. This finding suggests that LVSI is a much more common phenomenon than previously thought and questions current understanding of tumour metastasis.

Topics: Biomarkers, Tumor; Endometrial Neoplasms; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymphatic System; Neoplasm Invasiveness; Platelet Endothelial Cell Adhesion Molecule-1; Predictive Value of Tests; Sensitivity and Specificity; Staining and Labeling

The presence of metastases to regional lymph nodes (LN) is the single most important risk factor in endometrial cancer. Advances in molecular biology have provided more sensitive methods for detecting micrometastasis. This was a pilot study to determine whether cytokeratin staining of LN from endometrial cancer patients is more sensitive than traditional histopathologic evaluation for the detection of micrometastasis.. The inclusion criteria included patients with surgical stage I-II endometrial cancer having >50% myometrial invasion, lesions >2 cm, and negative LN together with one of the following: FIGO grade 3 or cervical or lymph-vascular involvement. A matched control group included patients with LN metastasis. The evaluation of the LN at the time of initial surgery consisted of a frozen section and a reevaluation on permanent sections with H&E. In the study, lymphadenectomy specimens were cut, stained again with H&E and with cytokeratin, and examined. Cytokeratin staining was performed with AE1/AE3 antibodies. There were 16 LN-negative cases and 9 LN-positive controls.. There was complete agreement between the LN assessment at time of surgery and the study H&E review prior to the staining for cytokeratin. However, 2 LN-negative cases (12.5%) had micrometastasis by cytokeratin staining. One of these patients developed recurrent disease in the para-aortic LN and died of disease at 2.8 years.. Cytokeratin staining may improve the sensitivity for detection of metastasis compared to traditional evaluation. This study strongly suggests that these micrometastasis are clinically significant. An approach incorporating cytokeratin analysis could improve the risk assessment of specific patients.

Topics: Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Pilot Projects; Risk Factors; Staining and Labeling

Minimal deviation endometrioid adenocarcinoma is a rare pathological variant of endometrioid adenocarcinoma. We describe a case representing another rare variant of endometrioid adenocarcinoma composed of both typical and minimal deviation endometrioid adenocarcinoma in a 45-year-old woman. Macroscopically, the cervix was of normal size but it had an indurated consistency. The myometrium was unremarkable. Microscopically, in addition to the typical endometrioid adenocarcinoma that involved 75% of the endometrium, there was a proliferation of mildly atypical endometrial type glands sparsely distributed in the fibrovascular tissue, typical of minimal deviation endometrioid adenocarcinoma. The latter component extended downward from the endomyometrial junction and involved focal areas of the uterine body and isthmus, diffusely invaded the entire cervix and focally the cervical resection margins. Focal transitional areas between typical and minimal deviation endometrioid adenocarcinoma were identified. Due to a relatively normal gross appearance and the microscopic deceptively benign looking appearance, minimal deviation endometrioid adenocarcinoma may pose problems of obtaining adequate sampling and evaluating the thickness of invasion of the endometrial carcinoma on gross, as well as microscopic, examination. HUM PATHOL 33:856-858.

Topics: Carcinoembryonic Antigen; Carcinoma, Endometrioid; Cervix Uteri; Endometrial Neoplasms; Female; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasm Invasiveness; Receptors, Estrogen; Receptors, Progesterone; Uterus; Vimentin

Primary squamous cell carcinoma of the endometrium (PSCCE) is an exceedingly rare tumor. Rarely are cytological criteria discussed. We report our experience in the cytological diagnosis of a case. A postmenopausal, 64-yr-old woman suffered from pyometria. An endometrial Pap smear displayed some malignant squamous cells. Curettage of the cervix and the uterine cavity only recovered some fragments of atypical squamous epithelium whose origin could not be precisely identified. A hysterectomy with bilateral adnexectomy was decided upon. Pathological study evidenced a primary squamous cell carcinoma in the uterine cavity while the cervix was tumor-free and the lymph nodes were devoid of metastases (pT1, pN0, pM0). The patient died 46 mo PO with multiple pulmonary and renal metastases. The histological feature of PSCCE is identical to that of any tumor of a similar nature, whatever the site, especially the cervix. Confirmation of the primary endometrial nature is only possible on the hysterectomy specimen.

Topics: Carcinoma, Squamous Cell; Dilatation and Curettage; Endometrial Neoplasms; Fatal Outcome; Female; Humans; Hysterectomy; Immunohistochemistry; Keratins; Kidney Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Mucin-1; Papanicolaou Test; Vaginal Smears

In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S-phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC-conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17) prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA-ploidy nor S-phase fraction were relevant prognostic parameters. But CV of the G(0)G(1)-peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA-aneuploidy (DNA-index > 1.3) and a high percentage of proliferating cells (>75th percentile) were univariate and multivariate highly significant prognostic factors for recurrence-free survival. Especially DNA-aneuploidy (DI>1.3) is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA-ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA-ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA-parameters was found.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; DNA, Neoplasm; Endometrial Neoplasms; Evaluation Studies as Topic; Female; Flow Cytometry; G1 Phase; G2 Phase; Humans; Keratins; Middle Aged; Mitosis; Multivariate Analysis; Neoplasm Recurrence, Local; Ploidies; Predictive Value of Tests; Prognosis; Resting Phase, Cell Cycle; S Phase; Survival Analysis; Uterine Cervical Neoplasms

The histological distinction between a primary endometrial and a primary endocervical adenocarcinoma is often difficult, especially in small biopsy specimens. A preoperative distinction is important because primary surgical management differs between the two tumors. Cases of primary endometrioid endometrial (n=30) and primary endocervical (n=26) adenocarcinoma of endocervical type were stained immunohistochemically with the monoclonal antibodies against carcinoembryonic antigen (CEA), vimentin, estrogen receptor (ER), and 34 beta E12. In all cases the origin of the adenocarcinoma was confirmed by examination of the definitive pathology specimen. There was diffuse positive nuclear staining for ER in 28 of 30 (93%) endometrial adenocarcinomas. ER was negative in 16 of 26 endocervical adenocarcinomas, and there was focal weak nuclear staining in the other cases. Vimentin was positive in 29 of 30 (97%) endometrial adenocarcinomas but in only 2 of 26 (8%) endocervical adenocarcinomas. CEA was positive in 25 of 26 (96%) endocervical adenocarcinomas, mostly with diffuse membranous and cytoplasmic staining. Positivity with CEA was present in 21 of 30 (70%) endometrial adenocarcinomas but was largely confined to squamoid areas with only 12 tumors exhibiting focal membranous staining of the glandular component. 34 beta E12 was diffusely positive in all except one cervical adenocarcinoma. In endometrial carcinomas, positivity was strongest in squamoid areas but there was positive staining, either focally or diffusely, of the glandular component in 27 cases. In summary, primary endometrioid endometrial adenocarcinomas are characterized by diffuse, strong, positive staining for vimentin and ER and negative or very focal, positive staining of the glandular component for CEA. In contrast, primary endocervical adenocarcinomas are characterized by CEA positivity, which is usually but not always diffuse, negativity for vimentin, and negativity or focal weak positivity for ER. 34 beta E12 is of no value in the distinction between endometrial and endocervical adenocarcinomas. A panel of immunohistochemical stains, comprising CEA, vimentin, and ER, generally allows confident preoperative distinction between a primary endometrial and endocervical adenocarcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Receptors, Estrogen; Uterine Cervical Neoplasms; Vimentin

We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Mucin-1; Uterine Cervical Neoplasms; Vimentin

Pulmonary metastases of endometrial stromal sarcoma (ESS) are uncommon and can pose diagnostic problems. We reviewed lung specimens from 16 patients with metastatic ESS. Patients were 31-77 years of age at the time of lung biopsy. Uterine ESSs were diagnosed an average of 9.8 years before lung biopsy in 11 patients. Uterine ESSs were originally called smooth muscle tumors in three additional patients. Thirteen patients were evaluated for new pulmonary nodules, seven of whom were asymptomatic. Nodules were multiple in 14 and solitary in four, ranging from 1.0 to 8.0 cm in greatest dimension. One patient died of metastatic disease; 14 were alive and seven of these were without disease (mean follow-up 4.1 years). Diagnostic considerations in 12 consultation cases included ESS, sclerosing hemangioma, carcinoid tumor, lymphangioleiomyomatosis, endometriosis, hemangiopericytoma, and lymphoma. Tumors were well circumscribed and usually solid, composed of plump spindle cells arranged in short fascicles. Two tumors were predominantly cystic. Sex cord-like stromal differentiation was identified in three. Neoplastic cells stained for vimentin (93%), estrogen and progesterone receptor (100%), smooth muscle actin (57%), desmin (50%), and keratin (46%). Metastatic ESS should be included in the differential diagnosis of nonepithelial neoplasms in women.

Topics: Actins; Adult; Aged; Desmin; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Sarcoma, Endometrial Stromal; Vimentin

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

Metaplastic differentiation, including squamous, mucinous, and tubal (ciliated), is common in both benign and neoplastic endometrium, and the cell of origin for this pathway is poorly understood. In this study, expression of a marker for basal and reserve cells in cervical squamous mucosa, designated p63, was investigated in a spectrum of endometrial alterations.. One hundred ninety different endometria from 132 patients were examined, including fetal (6), premenarchal (3), benign cyclic (29) and noncyclic (54), hyperplastic (14), and neoplastic (93) endometrial glandular epithelia. The latter included conventional endometrioid carcinomas with and without mucinous, ciliated, and squamous metaplasia, and uterine papillary serous carcinoma (UPSC).. p63 expression was identified in basal/subcolumnar cells in the fetal endometrium in a distribution similar to that in basal/reserve cells of the cervix. Staining was confined to individual scattered basal and suprabasal cells in cycling endometrium. In polyps and postmenopausal endometria, focal clusters of p63-positive cells were identified in inactive glands or surface epithelium. Metaplastic (squamous or mucinous) epithelia, either alone or in conjunction with hyperplasias or carcinomas, exhibited the most intense staining, primarily in basal or subcolumnar cells. In some cases, immediately adjacent nonmetaplastic columnar epithelium also stained positive. UPSCs contained only rare scattered p63-positive cells.. Cells with a basal or reserve cell phenotype exist in the endometrium during fetal life, are not conspicuous during the reproductive years, but may emerge during shifts in differentiation. Whether these cells signify specialized multipotential endometrial cells is not clear, but the similarity of these cells to basal/reserve cells of the cervix and their association with neoplasia merit further study.

Topics: Animals; Biomarkers, Tumor; Cell Differentiation; DNA-Binding Proteins; Endometrial Neoplasms; Endometrium; Epithelial Cells; Female; Genes, Tumor Suppressor; Humans; Immunophenotyping; Keratin-14; Keratins; Membrane Proteins; Menstrual Cycle; Metaplasia; Mice; Phosphoproteins; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins

Even after curative resection of early endometrial cancer, some patients die as a result of recurrence. We believe that these patients likely had occult lymph node metastases at the time of diagnosis. In an attempt to identify the responsible occult metastases, the clinicopathological significance of cytokeratin expression in lymph nodes with unconfirmed metastasis was evaluated retrospectively in patients with endometrial carcinoma.. We examined 304 pelvic lymph nodes and 46 primary tumors excised from 46 patients with endometrial cancer, including 36 with Stage I disease and 10 with Stage IIIc disease. Formalin-fixed paraffin-embedded tissue sections were stained immunohistochemically using antibodies against cytokeratin, CA125, and macrophage-related antigen. Sections were also stained with hematoxylin and eosin.. In 10 patients with Stage IIIc disease, cytokeratin expression was detected in cells other than the tumor cells in all 13 lymph nodes with metastasis and also in 20 (30.3%) of 66 lymph nodes without metastasis. Cytokeratin expression was observed in 37 (16.4%) of 225 lymph nodes with unconfirmed metastasis, which were obtained from 14 of 36 patients with Stage I disease. Five of fourteen patients with lymph nodes expressing cytokeratin had recurrent disease in the pelvic cavity, while all 22 patients with unconfirmed cytokeratin expression in their lymph nodes showed no recurrence. Cytokeratin and CA125 were detected simultaneously on macrophages in lymph nodes. Cytokeratin expression in lymph nodes was closely related to lymph-vascular space involvement of the primary tumor, but was not related to either histological grade or depth of myometrial invasion. Multivariate analysis identified cytokeratin expression as an independent risk factor for recurrence in Stage I endometrial cancer.. The immunohistochemical expression of cytokeratin in lymph nodes with undetected metastases predicts occult metastasis to these nodes and is a risk factor for recurrence in early-stage endometrial cancer.

Topics: CA-125 Antigen; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Macrophage-1 Antigen; Neoplasm Recurrence, Local; Neoplasm Staging; Predictive Value of Tests

Noncancerous cells simulating adenocarcinoma cells may interfere with the analysis of peritoneal cytology (PC) in patients with endometrial carcinoma. Immunocytochemistry (ICC) may improve the diagnosis of PC.. PC slides from 115 patients with endometrial carcinoma were reviewed. Suspicious or positive cell clusters were recovered with a cell transfer method and were subjected to ICC for MOC-31, cytokeratin 5/6, and p53. Conventional Papanicolaou staining and ICC results were compared directly on the same cells.. By combined conventional and immunocytochemical PC (CONV-ICC-PC), cytodiagnosis was positive in 18 of 115 patients (15.7%) and suspicious in 3 of 115 patients (2.6%). According to a multivariate Cox regression analysis of patients with tumors confined to the uterus that included grade, myometrial invasion, cervical involvement, and CONV-ICC-PC, only CONV-ICC-PC was an independent prognostic factor (P < 0.05). A multivariate analysis for all of the patients studied that compared CONV-ICC-PC with staging variables revealed that only peritoneal metastasis (P < 0.0001) and lymph node metastasis (P < 0.01) were independent prognostic factors. When peritoneal metastases were excluded, CONV-ICC-PC (P < 0.01) and lymph node metastasis (P < 0.0025) were the independent prognostic factors. By cell transfer and p53 immunostaining in samples from 14 patients with malignant cells in their peritoneal washings, no deaths occurred among 5 patients with negative p53, whereas 5 of 9 patients with positive p53 died of disease at the time of data analysis.. MOC-31 immunostaining improves the diagnosis of PC in endometrial carcinoma. Positive PC is an important prognostic factor for patients with endometrial carcinoma confined to the uterus. The p53 positive cells in PC have possible prognostic significance.

Topics: Adult; Aged; Aged, 80 and over; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Peritoneum; Prognosis; Tumor Suppressor Protein p53

Disturbances in the regulation of cell proliferation and differentiation play an important role in the formation of neoplastic lesions. Consequently, abnormalities in apoptosis regulation may contribute to this process. Expression of a neoepitope on cytokeratin 18, unmasked by an early caspase cleavage event and recognized by the novel monoclonal antibody M30, is an indicator of early epithelial cell apoptosis. The purpose of this study was to evaluate the quantitative relation among apoptosis (M30), cell persistence (bcl-2), and proliferation (S-phase fraction; SPF) in malignant and benign endometrium.. Using multiparameter DNA flow cytometry on 54 formalin-fixed paraffin-embedded samples from benign (proliferative, secretory, inactive, and hyperplastic endometrium) and malignant (grades 1-3 endometrial adenocarcinoma) endometrial tissue, bcl-2 expression and M30 reactivity were assessed together with the SPF in the cytokeratin-positive epithelial cells.. Benign cyclic endometrium showed a relatively high bcl-2 expression and low M30 reactivity in the proliferative phase whereas in the secretory phase this relation was inverse. In endometrial hyperplasia the expression of bcl-2 was increased compared to that in secretory and postmenopausal endometrium, but still below the level of proliferative samples. The expression of M30 also increased compared to normal proliferative endometrium but did not reach the level of endometrium in the secretory phase of the menstrual cycle. In cancer the expression of bcl-2 decreased with the progression of differentiation grade. For M30 expression this relation was inverse. Overall there was a significant increase of M30 reactivity in cancerous compared to hyperplasia and normal cyclic endometrium.. Transition of endometrial epithelium from hyperplasia to cancer seems to involve both increased apoptosis and decreased bcl-2 expression. Flow cytometric evaluation of M30 and bcl-2 expression levels, with the SPF, in currettage specimens from postmenopausal patients complaining of bleeding provides a quantitative assessment of endometrial apoptosis, anti-apoptosis, and proliferation. Further studies are needed to determine the relationship among these three processes as indicators of the biological behavior of gynecological tumors.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Biomarkers, Tumor; Cell Transformation, Neoplastic; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Flow Cytometry; Humans; Keratins; Middle Aged; Precancerous Conditions; Proto-Oncogene Proteins c-bcl-2; S Phase

Expression of a neoepitope on cytokeratin 18, recognized by the monoclonal antibody M30, is an early indicator of apoptosis in epithelial cells. The aim of this study was to determine the equilibrium between apoptosis (M30), anti-apoptosis (bcl-2), and proliferation (Ki-67) in different endometrial conditions. Paraffin-embedded samples (n = 107), representing proliferative endometrium (18), secretory endometrium (19), postmenopausal endometrium (15), disordered proliferative endometrium (6), simple hyperplasia (12), complex hyperplasia (8), and endometrial adenocarcinoma (29), were evaluated immunohistochemically. The indirect streptavidin-biotin-horseradish peroxidase technique, with 3-amino-9-ethylcarbazole as the chromogen, was used to visualize the reactions. Proliferative endometrium showed high bcl-2 and Ki-67 expression levels with no M30. In the secretory phase, the balance was tipped in favor of M30 with a decrease of bcl-2 and Ki-67. Postmenopausal endometrium revealed high Ki-67 and bcl-2 expression levels and no M30. In complex hyperplasia, M30, bcl-2, and Ki-67 showed increased expression. In endometrial carcinoma, an increasing reactivity for M30 and Ki-67 was seen as the grade progressed. bcl-2 reacted weakly and only in grade 1 cancer. Immunohistochemistry facilitates the study of the expression of proteins related to cyclic endometrial activity. Interruption of these cyclic events is associated with specific disturbances in the expression patterns of these proteins.

Topics: Apoptosis; Endometrial Neoplasms; Endometrium; Epithelium; Female; Humans; Keratins; Ki-67 Antigen; Postmenopause; Proto-Oncogene Mas; Proto-Oncogene Proteins c-bcl-2

Topics: Adenocarcinoma; Aged; Endometrial Neoplasms; Female; Granuloma, Foreign-Body; Histiocytes; Humans; Keratins; Peritoneal Diseases

To clarify the correlation between multidirectional differentiation and aggressiveness of endometrial adenocarcinomas, we assessed both proliferative activities (PA) using Ki-67 expression and squamous and/or endocrine differentiation. We divided 51 adenocarcinomas into 22 adenocarcinomas with typical squamous differentiation (>/=10% of tumor cells, typical SQ) classified into 10 adenoacanthomas (AA) and 12 adenosquamous carcinomas (AS), 17 adenocarcinomas with focal squamous differentiation (<10% of tumor cells), and 12 typical adenocarcinomas without morphological squamous differentiation (pure AC), according to the new WHO classification. Paraffin-embedded sections were stained using monoclonal antibodies against high-molecular-weight keratins (HMWK) to recognize squamous cells, chromogranin A to recognize endocrine cells, and Ki-67 antigen to recognize proliferating cells. Both AA and AS exhibited lower PA than pure AC. Typical SQ exhibited lower PA than pure AC. This difference was also significant after selecting only grade 1 or stage I/II cases. AA exhibited lower PA than AS and also after selecting only grade 1 or stage I/II cases. PA of adenocarcinoma with the expression of HMWK in >/=30% of tumor cells was lower than those without HMWK. PA of adenocarcinoma with the expression of chromogranin A in >/=10% of tumor cells was lower than those without chromogranin A. These differences were also significant after selecting only grade 1 or stage I/II cases. Squamous and/or endocrine differentiation is a good marker for a reduction of PA. Endometrial adenocarcinomas with multidirectional differentiation exhibited lower PA and were likely to be more mature than those with monodirectional differentiation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Adenosquamous; Cell Transformation, Neoplastic; Chromogranin A; Chromogranins; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Metaplasia; Middle Aged; Neoplasm Invasiveness

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

To examine the relationship between the morphology and the motility of cancer cells, we studied the difference between human endometrial undifferentiated cancer cell lines with different motilities, using light and electron microscopy, immunocytochemistry and RT-PCR. In a transplanted tumor of a cell line with high motility, many connective tissues and microvessels were observed and there were few intercellular spaces, which were ultrastructurally full of extracellular matrix. In the high-motility cell line only cytokeratin 19 was observed, and the level of cytokeratin 19 mRNA was elevated. Thus, motility is suggested to be related to the induction of connective tissues and cytoskeleton.

Topics: Animals; Cell Movement; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Confocal; Microscopy, Electron; Neoplasm Transplantation; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

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

Topics: Carcinoma, Transitional Cell; Diploidy; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged

To report a case of metastasis to the iris from endometrial carcinoma.. Case report. A 67-year-old woman with a history of endometrial carcinoma and local recurrence after surgery presented 11 months later with two yellow-pink nodules on the iris of the right eye.. Systemic medical evaluation demonstrated no other metastases. The iris tumors were removed surgically, and histology demonstrated adenocarcinoma consistent with endometrial carcinoma.. Endometrial carcinoma can metastasize to the iris. This possibility should be considered because the frequency of endometrial carcinoma is increasing.

Topics: Adenocarcinoma; Aged; Anterior Chamber; Endometrial Neoplasms; Female; Humans; Immunoenzyme Techniques; Iris Neoplasms; Keratins; Ultrasonography

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

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

Cytokeratins are constituents of the intermediate filaments of epithelial cells which are expressed in various combinations depending on the epithelial type and the degree of differentiation. The recently identified cytokeratin-20 (CK-20) was found with immunohistochemical methods to be expressed in gastrointestinal epithelium, uroepithelial cells, and Merkel cells. Clues were also found for low expression of CK-20 in endometrial carcinoma cells. The aim of this study was to examine whether CK-20 expression can be measured in endometrial carcinoma with the more sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) methods and therefore used as a potential diagnostic tumor biomarker for endometrial carcinoma.. In the present study we have used RT-PCR methods to determine expression of CK-20 in endometrial epithelial cells. Endometrial specimens were collected from 18 patients with endometrial carcinoma and 22 patients that underwent hysterectomy due to benign diseases. The specimens were prepared for both RT-PCR and immunohistochemical analysis. RNA, of the various cell pellets, was extracted and RT-PCR was performed with CK-20 and CK-19 primers (CK-19 was used as a marker for normal epithelial cells). Immunohistochemistry was carried out with the avidin-biotin-peroxidase complex method on formalin-fixed paraffin sections using CK-20 antibody.. CK-20 amplification band (370 bp) was obtained with mRNA extracted from endometrial carcinoma cells of 17 of the patients with endometrial carcinoma (sensitivity, 94.4%). CK-20 was negative in 21 patients with benign endometrial disease (specificity, 91.3%). No positive results were obtained with the immunohistochemical methods.. These results indicate that RT-PCR of CK-20, because of its high sensitivity, is a potential biomarker for detecting endometrial carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; DNA Primers; Endometrial Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Polymerase Chain Reaction; RNA-Directed DNA Polymerase; Sensitivity and Specificity

Small-cell carcinoma of the endometrium is a rare neoplasm, and its aggressive behavior has been reported. We report a case of small-cell carcinoma occurring primarily in the endometrium of a 62-year-old woman with postmenopausal vaginal bleeding and lower abdominal pain. The excised uterus showed a necrotic polypoid mass and histologically displayed an endometrial small-cell carcinoma. Immuno-histochemically, the tumor cells were positive for cytokeratin, the epithelial membrane antigen, neuron-specific enolase, and chromogranin, but were negative for the leukocyte common antigen and Grimelius stain. Ultrastructural analysis revealed the presence of dense core granules in the cytoplasm of tumor cells. The patient died 2 months after surgery because of aggressive behavior of the tumor. We wish to distinguish small-cell carcinoma of the endometrium from conventional epithelial tumors of the endometrium, because of the former's distinctive histopathologic, immunohistochemical, and ultrastructural characteristics.

Topics: Carcinoma, Small Cell; Chromogranin A; Chromogranins; Cytoplasmic Granules; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Magnetic Resonance Imaging; Microscopy, Electron; Middle Aged; Mucin-1; Phosphopyruvate Hydratase; Tomography, X-Ray Computed; Urography

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

In The Netherlands an external quality control study of immunocytochemical (IC) staining of effusions was initiated, consisting of three test rounds. The 12 participating laboratories received samples of malignant effusions (runs 1, 2 and 3), and five unstained control specimens prepared from the same material in runs 2 and 3. The laboratories used their own protocols to prepare and stain the samples ('in-house' specimens). Two persons viewed and scored the slides following preset criteria concerning number and morphology of diagnostic cells, background staining and staining specificity. Better scoring results were found for control specimens, compared with 'in-house' specimens, primarily caused by cell loss in the latter. This finding underlines the view that high quality IC needs well organized processing and staining procedures, and warrants external quality control systems.

Topics: Breast Neoplasms; Carcinoembryonic Antigen; Endometrial Neoplasms; Exudates and Transudates; Female; Humans; Immunohistochemistry; Keratins; Netherlands; Quality Control; Vimentin

Keratins 8 (K8) and 18 (K18) are major components of intermediate filaments (IFs) of simple epithelial cells and tumors derived from such cells. Structural cell changes during apoptosis are mediated by proteases of the caspase family. During apoptosis, K18 IFs reorganize into granular structures enriched for K18 phosphorylated on serine 53. K18, but not K8, generates a proteolytic fragment during drug- and UV light-induced apoptosis; this fragment comigrates with K18 cleaved in vitro by caspase-6, -3, and -7. K18 is cleaved by caspase-6 into NH2-terminal, 26-kD and COOH-terminal, 22-kD fragments; caspase-3 and -7 additionally cleave the 22-kD fragment into a 19-kD fragment. The cleavage site common for the three caspases was the sequence VEVD/A, located in the conserved L1-2 linker region of K18. The additional site for caspases-3 and -7 that is not cleaved efficiently by caspase-6 is located in the COOH-terminal tail domain of K18. Expression of K18 with alanine instead of serine at position 53 demonstrated that cleavage during apoptosis does not require phosphorylation of serine 53. However, K18 with a glutamate instead of aspartate at position 238 was resistant to proteolysis during apoptosis. Furthermore, this cleavage site mutant appears to cause keratin filament reorganization in stably transfected clones. The identification of the L1-2 caspase cleavage site, and the conservation of the same or very similar sites in multiple other intermediate filament proteins, suggests that the processing of IFs during apoptosis may be initiated by a similar caspase cleavage.

Topics: Adenocarcinoma; Animals; Apoptosis; Caspase 3; Caspase 6; Caspase 7; Caspases; Cysteine Endopeptidases; Endometrial Neoplasms; Enzyme Precursors; Epithelium; Female; Gene Expression; Humans; Intermediate Filaments; Keratins; Mice; Molecular Sequence Data; Mutagenesis; Peptide Mapping; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Tumor Cells, Cultured

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 compare histologically and stereologically the endometriotic nodule of the rectovaginal septum to peritoneal endometriosis.. Morphometric investigation, cytokeratin and vimentin content, and steroid receptor evaluation were performed on endometriotic tissue from the peritoneum (n = 52) and rectovaginal nodules (n = 68).. An academic teaching hospital.. Biopsies were taken from 120 patients undergoing a laparoscopy for infertility and/ or pelvic pain (52 from typical black peritoneal endometriotic implants and 68 from endometriotic nodule of the rectovaginal septum). None of the patients were treated.. Mitotic activity was found to be significantly different in peritoneal and rectovaginal endometriosis. The evaluation suggested that the stroma is not mandatory for the invasion of glandular epithelium in the rectovaginal nodule, which is, like a adenomyoma, a circumscribed nodular aggregate of smooth muscle and glandular elements. Cytokeratin and vimentin content as well as the estrogen receptor (ER) and P receptor (PR) content were significantly lower in both types of lesion when compared with eutopic endometrium. But vimentin immunoreactivity in epithelium, as well as the ER and PR content, were significantly lower in nodules when compared with black peritoneal lesions.. It is suggested that the rectovaginal endometriotic nodule is a different disease from peritoneal endometriosis and must be called rectovaginal adenomyosis or rectovaginal adenomyoma. Its histopathogenesis probably is not related to the implantation of regurgitated endometrial cells but to the metaplasia of Müllerian rests.

Topics: Adenomyoma; Biopsy; Diagnosis, Differential; Endometrial Neoplasms; Endometriosis; Endometrium; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Mitosis; Peritoneal Diseases; Receptors, Estrogen; Receptors, Progesterone; Rectal Diseases; Vaginal Diseases; Vimentin

The female genital tract is an infrequent site of metastasis, particularly for extragenital primaries. The ovary and vagina are the sites within the female genital tract that are the most frequently affected. The uterine corpus, especially the endometrium, is a distinctly unusual site of involvement. Primary lung cancer is the source of metastatic tumor to the female genital tract in less than 5% of patients. In the reported instances of endometrial involvement by a primary lung cancer, adenocarcinoma has been the reported subtype. Here, we report a case of well-differentiated neuroendocrine carcinoma of the lung metastatic to the endometrium in a 68-year-old woman with postmenopausal bleeding. Immunohistochemical studies were performed to confirm the neuroendocrine nature of the neoplasm.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Endometrial Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Nerve Tissue Proteins

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

We report on six patients with tumours of visceral organs (three patients with endometrial adenocarcinoma with squamous cell differentiation, one patient with atypical hyperplasia of endometrium, and two patients with adenocarcinoma of the colon with squamous cell differentiation), where unquestionable differentiation into shadow cells was observed. In all six cases the shadow cells were found mostly in the morules of immature squamous cells. The shadow cells were morphologically identical, on the light microscopical and ultrastructural level, to similar cells found in pilomatricomas. They were often accompanied by granulomatous giant cell reaction and calcification.

Topics: Adenocarcinoma; Adult; Carcinoma, Squamous Cell; Cell Differentiation; Colonic Neoplasms; Endometrial Neoplasms; Endometrium; Female; Humans; Hyperplasia; Keratins; Male; Microscopy, Electron; Middle Aged; Uterine Neoplasms; Uterus

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

The expression of epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) was compared with the presence of "squamous differentiation" (SD) visualized in various histotypes of endometrial carcinoma by using a panel of monoclonal antibodies. The results of the current study demonstrate that EGFr and TGF-alpha are present in routinely processed endometrial carcinoma. The highest positive EGFr and TGF-alpha expression was seen in the group of adenocarcinomas with SD. The more intense EGFr and TGF-alpha immunoreactivity was observed in "squamous" foci both in adenoacanthomas (AA) and in adenosquamous carcinomas (AS). These EGFr- and TGF-alpha-positive squamous areas prevalently displayed a "stratification-related" cytokeratin (CK) immunoprofile characterized by the expression of CKs 1, 4, 5, 10, 13, 14, and 16. No correlation was found between EGFr- and TGF-alpha-positive status and depth of myometrial invasion or surgical stage. These results clearly demonstrate that EGFr and TGF-alpha expression is related remarkably to endometrial carcinoma with "squamous" areas both morphologically and immunophenotypically. This specific association leads us to suggest that EGFr and TGF-alpha expression in endometrial carcinoma may be prevalently involved in the equilibrium of cell differentiation of the "squamous" foci commonly observed in this group of neoplasias.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Carcinoma, Adenosquamous; Cell Differentiation; Endometrial Neoplasms; ErbB Receptors; Female; Humans; Immunohistochemistry; Keratins; Metaplasia; Middle Aged; Transforming Growth Factor alpha

Primary squamous cell carcinomas of the endometrium are rare tumours. We have studied 7 primary and 2 secondary squamous cell carcinomas immunohistochemically with anti-all-cytokeratin (KL 1), anti-CEA and anti-vimentin. The non-keratinizing carcinomas and the non-keratinizing component of the keratinizing carcinomas showed a strong expression of vimentin. Contrary to this, the keratinizing parts were strongly positive with anti-CEA. Additionally, some cases showed a direct transformation of the (dysplastic) glandular endometrial epithelium into neoplastic squamous cells. These findings suggest that the primary squamous cell carcinoma of the endometrium is the result of a bidirectional differentiation of pluripotent endometrial precursor cells. Like in other non-endometrioid adenocarcinomas, such metaplasias develop from pluripotent Müllerian epithelium. They show various differentiations, perhaps endocervical determination with keratinization and positive reaction against CEA or primitive endometrioid with squamous cell appearance, positive anti-vimentin reaction and non-keratinization.

Topics: Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Vimentin

The endometrial carcinoma cell lines EC-MZ-1, 2, 3, 5, 9, and 11 were established between 1986 and 1990. Four cell cultures were started from endometrial tissue, one from ascites, and one from a lymph node metastasis. Lines have to date been subcultured up to 180 times and the doubling time varies between 26 hr and 3 weeks. Immunocytochemically the coexpression of cytokeratin (predominantly simple-epithelial cytokeratin polypeptides) and vimentin intermediate filaments was detectable in all cell lines, but three lines (EC-MZ-5, 9, 11) expressed vimentin only at low level. By transmission electron microscopy the tumor cells exhibited features of epithelial differentiation. After subcutaneous transplantation into nude mice three lines (EC-MZ-1, 2, 5) produced slow-growing tumors. The histological classification of these tumors ranged from moderately differentiated adenocarcinoma to undifferentiated carcinoma and closely corresponded to the original tumor. Even after long-term in vitro culture, without any addition of estrogens to the culture medium, the moderately differentiated receptor-positive cell line (EC-MZ-2) retained its morphological differentiation. The cells were propagated without estrogens in the culture medium. The estrogen and progesterone receptor levels of cultured cells were determined. Three lines (EC-MZ-1, 2, 3) were positive for the progesterone receptor in low passage number only, the other cell lines were negative for both receptors. The transplantable lines were investigated for hormonal receptor expression in ovariectomized nude mice. In the moderately differentiated cell line (EC-MZ-2) we observed an enhanced expression of the estrogen receptor under optimal stimulation of the nude mouse with estradiol benzoate. There was no effect on the expression of the progesterone receptor.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Adult; Aged; Aged, 80 and over; Animals; Carcinoma, Squamous Cell; Endometrial Neoplasms; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Mice; Mice, Nude; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Neoplasm Invasiveness; Neoplasm Transplantation; Receptors, Estrogen; Receptors, Progesterone; Tumor Cells, Cultured; Vimentin

Various grades of adenomatous hyperplasia represent precancerous states leading to the most common type of adenocarcinoma with endometrial differentiation. Grades 1 and 2 are characterized by architectural abnormalities only (complex hyperplasia). They rarely progress to carcinoma. Grade 3 in addition is characterized by cytological atypicalities (atypical hyperplasia) and shows a much higher progression rate into invasive carcinoma. Endometrial carcinomas may originate from endometrial glandular epithelium and show endometrial differentiation, or from various types of metaplasias developing in the endometrium from pluripotent Müllerian epithelium. They then show endocervical or serous papillary differentiation. Because of their differences in spread, speed of growth and survival rates, it is important to subclassify these endometrial carcinomas. Immunohistochemically, adenocarcinomas with endometrial differentiation including adenoacanthomas and adenosquamous carcinomas can be recognized by their coexpression of cytokeratin 8 and vimentin, and by their negative reaction for CEA. Distinction from adenocarcinomas with mucinous differentiation, including muceopidermoid adenocarcinomas, is possible by their negative reaction for vimentin and by their positive reaction for CEA. On the other hand, carcinomas with mucinous differentiation primarily located in the endometrium can not be distinguished from those primarily located in the endocervix by immunohistochemistry; that distinction must be made topographically. The same holds true for clear cell carcinomas of both locations. Over the past decade, mucinous adenocarcinomas and clear cell carcinomas originating from the endometrium have increased, whereas adenocarcinomas with endometrial differentiation have become less frequent. This shift is closely related to the altered postmenopausal hormone substitution with the addition of the synthetic gestagens. These apparently stimulate proliferation of endocervical epithelium not only in the endocervix, but also that arising in endocervical metaplasias of the endometrium.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Diagnosis, Differential; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Precancerous Conditions; Vimentin

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