bromochloroacetic-acid and Endometriosis

Two cases of invasive carcinoma developing in extragonadal endometriosis are presented. Each case had a different clinical course. In addition to routine histopathologic studies immunohistochemical studies to assess the expression of cytoceratin and glycoprotein CD-44 were performed. In both cases CK-7 expression was higher in malignancy then in the endometrioid tissue. Very high expression of CD-44 protein (marker of metastatic potential) was found in patients with poor progress of the disease.

Topics: Abdomen; Adult; Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Endometriosis; Female; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Keratin-7; Keratins; Perineum; Skin Neoplasms; Up-Regulation

Endometriosis is a prevalent gynecologic disease, defined by dysfunctional endometrium-like lesions outside of the uterine cavity. These lesions are presumably established via retrograde menstruation, i.e., endometrial tissue that flows backwards during menses into the abdomen and deposits on the organs. As ongoing pain is one of the main pain symptoms of patients, an animal model that illuminates this problem is highly anticipated. In the present study, we developed and validated a rat model for ongoing endometriosis-associated pain. First, menstrual endometrial tissue was successfully generated in donor rats, as validated by gross examination, histology and qPCR. Next, endometriosis was induced in recipient animals by intraperitoneal injection of menstrual tissue. This resulted in neuro-angiogenesis as well as established endometriosis lesions, which were similar to their human counterparts, since epithelial and stromal cells were observed. Furthermore, significant differences were noted between control and endometriosis animals concerning bodyweight and posture changes, indicating the presence of ongoing pain in animals with endometriosis. In summary, a rat model for endometriosis was established that reliably mimics the human pathophysiology of endometriosis and in which signs of ongoing pain were detected, thus providing a new research tool for therapy development.

Topics: Animals; Disease Models, Animal; Endometriosis; Endometrium; Female; GAP-43 Protein; Keratins; Menstruation; Pain; Rats; Stromal Cells; Vimentin

Endometriosis is a common disorder of unknown etiology, and non-surgical therapies are still a challenge. To understand the pathogenesis and preclinical testing of drugs for endometriosis, animal models are highly desirous. Herein, we carried out longitudinal characterization of a mouse model for endometriosis where uterine tissue was transplanted onto the intestinal mesentery. During the course of lesion development from day 15 to 60 post-induction, the ectopic endometrium became pale, fluid-filled and the animals developed peritoneal adhesions. Most lesions resembled a well-differentiated type of endometriosis and ~13% of animals had mixed type of lesions. There was extensive stromal compaction in the ectopic tissue. During the progression of endometriosis, there was increased proliferation of epithelial and stromal cells as evident by PCNA staining.

Topics: Animals; Aromatase; Cadherins; Cell Proliferation; Choristoma; Disease Models, Animal; Endometriosis; Endometrium; Epithelial Cells; Epithelial-Mesenchymal Transition; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Fibrosis; Gene Expression Regulation; Humans; Inflammation; Interferon-gamma; Interleukin-1beta; Keratins; Mesentery; Mice; Myofibroblasts; Proliferating Cell Nuclear Antigen; Stromal Cells; Transplantation, Autologous; Transplantation, Heterotopic; Tumor Necrosis Factor-alpha

Endometriotic lesions are composed in part of endometrial-like stromal cells, however, there is a shortage of immortalized human endometrial stromal cultures available for research. As genetic factors play a role in endometriosis risk, it is important that genotype is also incorporated into analysis of pathological mechanisms. Human telomerase reverse transcriptase (hTERT) immortalization (using Lenti-hTERT-green fluorescent protein virus) took place following genotype selection; 13 patients homozygous for either the risk or non-risk 'other' allele for one or more important endometriosis risk single nucleotide polymorphism on chromosome 1p36.12 (rs3820282, rs56318008, rs55938609, rs12037376, rs7521902 or rs12061255). Short tandem repeat DNA profiling validated that donor tissue matched that of the immortalized cell lines and confirmed that cultures were genetically novel. Expression of morphological markers (vimentin and cytokeratin) and key genes of interest (telomerase, estrogen and progesterone receptors and LINC00339) were examined and functional assays for cell proliferation, steroid hormone and inflammatory responses were performed for 7/13 cultures. All endometrial stromal cell lines maintained their fibroblast-like morphology (vimentin-positive) and homozygous endometriosis-risk genotype following introduction of hTERT. Furthermore, the new stromal cultures demonstrated positive and diverse responses to hormones (proliferation and decidualisation changes) and inflammation (dose-dependent response), while maintaining hormone receptor expression. In conclusion, we successfully developed a range of human endometrial stromal cell lines that carry important endometriosis-risk alleles. The wider implications of this approach go beyond advancing endometriosis research; these cell lines will be valuable tools for multiple endometrial pathologies offering a level of genetic and phenotypic diversity not previously available.

Topics: Adult; Biomarkers; Cell Line, Transformed; Cell Proliferation; Chromosomes, Human, Pair 1; Endometriosis; Endometrium; Female; Founder Effect; Gene Expression; Genotype; Homozygote; Humans; Keratins; Microsatellite Repeats; Polymorphism, Single Nucleotide; Receptors, Estrogen; Receptors, Progesterone; Risk; RNA, Long Noncoding; Stromal Cells; Telomerase; Vimentin

Lipocalin 2 (LCN2) is an induced stressor that promotes the epithelial-mesenchymal transition (EMT). We previously demonstrated that the development of endometriosis in mice correlates with the secretion of LCN2 in the uterus. Here, we sought to clarify the relationship between LCN2 and EMT in endometrial epithelial cells and to determine whether LCN2 plays a role in endometriosis. Antibodies that functionally inhibit LCN2 slowed the growth of ectopic endometrial tissue in a mouse model of endometriosis, suggesting that LCN2 promotes the formation of endometriotic lesions. Using nutrient deprivation as a stressor, LCN2 expression was induced in cultured primary endometrial epithelial cells. As LCN2 levels increased, the cells transitioned from a round to a spindle-like morphology and dispersed. Immunochemical analyses revealed decreased levels of cytokeratin and increased levels of fibronectin in these endometrial cells, adhesive changes that correlate with induction of cell migration and invasion. Lcn2 knockdown also indicated that LCN2 promotes EMT and migration of endometrial epithelial cells. Our results suggest that stressful cellular microenvironments cause uterine tissues to secrete LCN2 and that this results in EMT of endometrial epithelial cells, which may correlate with the development of ectopic endometriosis. These findings shed light on the role of LCN2 in the pathology of endometrial disorders.

Topics: Acute-Phase Proteins; Animals; Antibodies; Cell Movement; Cells, Cultured; Disease Models, Animal; Endometriosis; Endometrium; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Fibronectins; Keratins; Lipocalin-2; Lipocalins; Male; Mice; Oncogene Proteins; Uterus

Angiogenesis is a prerequisite for endometriotic lesion formation and development. Pigment epithelium-derived factor (PEDF) is a potential inhibitor of angiogenesis. The objective of this study was to detect PEDF immunolocalization in endometriotic lesions and the correlation with vascular endothelial growth factor (VEGF) and microvascular density (MVD) in a rat model of endometriosis. A subcutaneous endometriosis rat model was established by using auto-transplantation. Expression of PEDF, VEGF and MVD labeled by von Willebrand factor (v-WF) in endometriotic lesions and endometrial tissues was evaluated using immunohistochemical staining. We detected lower PEDF immunostaining and higher VEGF and MVD immunostaining in active lesions in a rat model of endometriosis than that in endometriosis endometrium or control endometrium (P<0.05), but no differences between endometriosis and control endometrium were found (P>0.05). In lesions, PEDF expression was negatively correlated with VEGF expression, MVD or sizes of cysts (P<0.01). On the contrary, both VEGF expression and MVD were positively correlated with lesion sizes (P<0.05). In addition, VEGF expression was positively correlated with MVD (P<0.01). Our results suggest that PEDF might be involved in the pathogenesis of endometriosis and may lead to novel treatment for this disease.

Topics: Animals; Disease Models, Animal; Endometriosis; Endometrium; Eye Proteins; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Keratins; Nerve Growth Factors; Rats; Rats, Sprague-Dawley; Serpins; Vascular Endothelial Growth Factor A; Vimentin

Endometrium is derived from intermediate mesoderm via mesenchymal to epithelial transition (MET) during development of the urogenital system. By retaining some imprint of their mesenchymal origin, endometrial epithelial cells may be particularly prone to return to this state, via epithelial to mesenchymal transition (EMT). We hypothesized that pelvic endometriosis originates from retrograde menstruation of endometrial tissue and that EMT-like and MET-like processes might be involved in the pathogenesis of pelvic endometriosis.. We investigated commonly used molecular markers for EMT, including cytokeratin, E-cadherin, N-cadherin, vimentin, S100A4 and dephosphorylated beta-catenin by immunohistochemistry in different forms of pelvic endometriosis: deep infiltrating endometriosis, ovarian endometriosis and superficial peritoneal endometriosis (red and black lesions), as well as samples of menstrual endometrium, other benign ovarian cysts (mucinous and serous cyst adenoma), and abdominal scar endometriosis for comparison.. Epithelial cells of red peritoneal lesions and ovarian endometriosis showed less epithelial marker (cytokeratin, P < 0.0001) expression and more mesenchymal marker (vimentin and/or S100A4, P < 0.0001) expression than those of menstrual endometrium. In contrast, epithelial cells of black peritoneal lesions and deep infiltrating endometriosis showed more epithelial marker (E-cadherin) expression than those of menstrual endometrium (P < 0.03), red peritoneal lesions (P < 0.0001) and ovarian endometriosis (P< 0.0001), but maintained expression of some mesenchymal markers (vimentin, S100A4). In addition, dephosphorylated beta-catenin protein expression was significantly higher in epithelial cells of deep infiltrating endometriosis (P < 0.0001) than in epithelial cells of red and black peritoneal lesions and ovarian endometriosis.. EMT-like and MET-like processes might be involved in the pathogenesis of pelvic endometriosis.

Topics: Adult; beta Catenin; Biomarkers; Cadherins; Cell Differentiation; Cicatrix; Endometriosis; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Humans; Keratins; Menstrual Cycle; Ovarian Cysts; S100 Calcium-Binding Protein A4; S100 Proteins; Vimentin

Immune-endocrine interplay may play a major role in the pathogenesis of endometriosis. In the present study, we have investigated the interaction between macrophage migration inhibitory factor (MIF), a major pro-inflammatory and growth-promoting factor markedly expressed in active endometriotic lesions, and estradiol (E(2)) in ectopic endometrial cells. Our data showed a significant increase of MIF protein secretion and mRNA expression in endometriotic cells in response to E(2). MIF production was blocked by Fulvestrant, an estrogen receptor (ER) antagonist, and induced by ERα and ERβ selective agonists propyl-pyrazole-triol (PPT) and diarylpropionrile (DPN), respectively, thus demonstrating a specific receptor-mediated effect. Cell transfection with MIF promoter construct showed that E(2) significantly stimulates MIF promoter activity. Interestingly, our data further revealed that MIF reciprocally stimulates aromatase protein and mRNA expression via a posttranscriptional mRNA stabilization mechanism, that E(2) itself can upregulate aromatase expression, and that inhibition of endogenous MIF, using MIF specific siRNA, significantly inhibits E(2)-induced aromatase. Thus, the present study revealed the existence of a local positive feedback loop by which estrogen acts directly on ectopic endometrial cells to upregulate the expression of MIF, which, in turn, displays the capability of inducing the expression of aromatase, the key and rate-limiting enzyme for estrogen synthesis. Such interplay may have a considerable impact on the development of endometriosis.

Topics: Adult; Aromatase; Endometriosis; Enzyme Induction; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Feedback, Physiological; Female; Gene Expression Regulation; Humans; Intramolecular Oxidoreductases; Keratins; Macrophage Migration-Inhibitory Factors; Neprilysin; Promoter Regions, Genetic; RNA Stability; RNA, Messenger; Stromal Cells; Vimentin

Decidualized endometrioma is a pseudoneoplastic lesion that may appear as a solitary nodule in the hypodermis, simulate a malignant epithelioid tumor, and can represent a diagnostic challenge. A 36-year-old woman delivered a full-term baby by cesarean. At the immediate puerperium, she complained of a subcutaneous nodule measuring 2.5 cm, underneath a previous caesarean scar from the former full-term delivery 3 years earlier. Histologic features included a nodular growth pattern of large monomorphic epithelioid cells showing diffuse positivity for cytokeratin (AE1/AE3, 18), human placental lactogen, and CD10 and focal positivity for inhibin alpha. The main differential diagnoses include trophoblastic neoplasia and deciduoid mesothelioma. Good clinicopathological correlation is essential for the correct diagnosis. Immunohistochemical stains can be misleading. An important clue is the combination of large decidualized cells and lumens lined by flat or low cuboidal cells that are atrophic endometrial glands. This lesion has a benign behavior.

Topics: Adult; Diagnosis, Differential; Endometriosis; Female; Gestational Trophoblastic Disease; Humans; Immunohistochemistry; Keratins; Mesothelioma; Pregnancy; Skin

To investigate the frequency of endometriotic lesions and disseminated endometriotic-like cells in a series of incidentally removed lymph nodes (LNs) in patients with endometriosis.. Retrospective study.. University hospital endometriosis center.. Premenopausal patients underwent surgery because of endometriosis-associated symptoms.. Retrospective analysis of 108 coincidentally resected LNs of 24 patients with endometriosis. To identify endometriotic cells, immunohistochemical analysis of estrogen and progestogen receptor (ER-PR), CD10, and cytokeratin was performed.. The occurrence of endometriotic lesions (ER-PR, CD10, and cytokeratin positive) and disseminated endometriotic-like ER-PR-positive cells in LNs.. Deep infiltrating endometriosis was diagnosed in 23 of the 24 patients with incidentally removed LNs. In 8 of 24 (33.3%) patients with incidentally removed LNs, typical endometriotic lesions were detected. Disseminated ER-PR-positive cells were found in 17 of 24 patients (70.8%). Lymph node involvement correlated directly with the deep infiltrating endometriosis lesional size.. Estrogen receptor-progestogen receptor-positive endometriotic lesions and disseminated endometriotic-like cells frequently are detected in LNs of patients with deep infiltrating endometriosis and, therefore, might reflect "nonlocalized" disease. If clinical significance of such lesions were provided, adjuvant hormonal treatment could be considered as a possible additional mode of therapy.

Topics: Adult; Endometriosis; Female; Humans; Immunohistochemistry; Incidental Findings; Keratins; Lymph Nodes; Middle Aged; Neprilysin; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Rectal Diseases; Retrospective Studies; Vaginal Diseases; Young Adult

Topics: Adenocarcinoma; Biomarkers; CA-125 Antigen; Colon, Sigmoid; Colonic Diseases; Colonic Neoplasms; Colonoscopy; Diagnosis, Differential; Endometriosis; Female; Humans; Keratins; Middle Aged; Receptors, Estrogen; Tomography, X-Ray Computed

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

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

Bone marrow-derived cells (BMDCs) can differentiate into nonhematopoietic cells, suggesting that BMDCs may contribute to the maintenance of multiple tissues. Donor-derived bone marrow cells have been identified in human uterine endometrium. Here, two murine models were used to investigate the contribution of nonendometrial stem cells to endometrium. We investigate whether BMDCs can localize to uterine endometrium and to endometriosis. After bone marrow transplantation, male donor-derived bone marrow cells were found in the uterine endometrium of female mice. Although uncommon (<0.01%), these cells can differentiate into epithelial cells. After generation of experimental endometriosis by ectopic endometrial implantation in the peritoneal cavity, bone marrow from LacZ transgenic mice was used for transplantation. LacZ expressing cells were found in the wild-type ectopic endometrium implanted in the peritoneal cavity of hysterectomized LacZ transgenic mice. The repopulation of endometrium with bone marrow-derived stem cells may be important to normal endometrial physiology and also may help to explain the cellular basis for the high long-term failure of conservative alternatives to hysterectomy. The examination of a sexually dimorphic organ such as the uterus demonstrates the ability of male bone marrow, which cannot harbor circulating endometrial cells, to generate endometrium de novo and proves their mesenchymal stem cell origin. Finding Y chromosome bearing endometrial cells demonstrates the potential to recapitulate embryonic developmental pathways that were never activated in males; BMDCs may have vast regenerative capacity. Additionally, the ability of stem cells to engraft endometriosis has implications for the origin and progression of this disease. Ectopic differentiation of stem cells may be a novel mechanism of disease. Disclosure of potential conflicts of interest is found at the end of this article.

Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Cell Movement; Choristoma; Endometriosis; Endometrium; Female; Keratins; Lac Operon; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic

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

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

To establish a mouse model for endometriosis and to evaluate roles of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in the formation of disease.. Experimental laboratory study.. A women's hospital in China.. Ten women with endometriosis and 10 control women, as well as ICR mice.. Endometrial fragments were transplanted in the peritoneal cavities of mice at minilaparotomy. Transplants were observed and then removed for the assessment of morphology and immunohistochemical staining of VEGF and MMP-2.. Observation of transplants, expression of VEGF and MMP-2.. On days 1 and 2, glandular and stromal cells were viable at the margins of transplants. On day 3, the transplants were surrounded by mesothelial cells, and the endometrial glands and stromal cells were clearly viable at the interface. The scores of VEGF and MMP-2 of viable glandular cells of transplants were increased compared with the ones before transplantation. The scores of VEGF and MMP-2 of transplants from women with endometriosis were higher than those of control women.. Endometrial transplants from the patients with endometriosis express more VEGF and MMP-2 than endometrium in control women, suggesting that VEGF and MMP-2 may expedite the formation of endometriosis in its early stage.

Topics: Animals; Disease Models, Animal; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Matrix Metalloproteinase 2; Mice; Mice, Inbred ICR; Neprilysin; Tissue Transplantation; Vascular Endothelial Growth Factor A

Immunological therapies have shown promising results in the treatment of endometriosis. Mycobacteria are one of the most common immune therapies used in other diseases. We have assessed the effects of mycobacteria in altering the ability of peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cells to kill endometrial stromal cells using an in vitro model. This may have implications in the immunotherapy of endometriosis.. Primary cultures of endometrial stromal cells were grown from female patients and PBMCs were extracted from healthy female volunteers. Effector cells (PBMCs or NK cells) were exposed to varying concentrations of mycobacteria before their ability to kill cultured endometrial cells was tested using a 51Cr-release assay.. Treatment of effector cells with the Connaught Substrain Bacillus of Calmette and Guérin (BCG) led to increased killing of target cells by PBMCs and NK cells. The optimal concentration for treatment of effector cells with Connaught BCG was approximately 0.1 multiplicities of infection (m.o.i.). There was a trend towards increased killing after treatment with Pasteur BCG. CD56+ (NK) cells treated with BCG at 0.1 m.o.i. showed increased killing of target cells compared with untreated effector cells.. Endometrial stromal cells are susceptible to killer cells activated by mycobacteria. This in vitro work suggests a possible role for mycobacteria in the immunotherapy of endometriosis.

Topics: Adult; Biological Therapy; CD56 Antigen; Cells, Cultured; Endometriosis; Endometrium; Female; Humans; Immunotherapy; Keratins; Killer Cells, Natural; Leukocytes, Mononuclear; Mycobacterium bovis; Stromal Cells; Vimentin

Topics: Adenoma; Adult; Biopsy; Colonic Diseases; Colonic Neoplasms; Colonoscopy; Diagnosis, Differential; Endometriosis; Female; Humans; Keratins; Magnetic Resonance Imaging

The clinicopathologic features of a case of endometrioid adenocarcinoma arising from colonic endometriosis that clinically and histologically mimicked a primary colonic carcinoma are reported. The differential diagnostic features of the tumor leading to the correct diagnosis included associated endometriosis, a minor mucosal component, focal squamous differentiation, absence of dirty necrosis, low nuclear grade, absence of a colonic adenoma, and a CK7+/CK20-/CEA- immunophenotype.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Colonic Diseases; Colonic Neoplasms; Diagnosis, Differential; Endometriosis; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins

The chick embryo chorioallantoic membrane (CAM) bioassay was used to investigate the early pathogenesis of endometriosis. Endometrial fragments were explanted onto the CAM. The grafts including the surrounding CAM were excised at 24, 48 or 72 h after explantation, fixed and embedded in paraffin. Immunohistochemical analysis was used to distinguish endometrial cells. To identify cells of human origin, in-situ hybridization was performed using a probe specific for human chromosome 1. After 24 h, direct contact between endometrial stromal as well as epithelial cells and the mesenchymal layer of the CAM was observed. Invasion of both stromal cells and intact endometrial glands into the mesenchymal layer was observed after 48 h. At 72 h, endometriosis-like lesions were observed in the mesenchymal layer. Positive staining with antibodies to vimentin and pan-cytokeratin was observed in the invading cells as well as in the lesions. In the lesions these positively stained cells showed in-situ hybridization signals for human chromosome 1, confirming their human origin. In conclusion, after 3 days of incubation, endometriosis-like lesions consisting of human endometrial glands and stromal cells were found in the mesenchymal layer of the CAM. These lesions apparently resulted from the invasion of intact human epithelial structures and stromal cells.

Topics: Allantois; Animals; Chick Embryo; Chorion; Endometriosis; Endometrium; Female; Fetal Tissue Transplantation; Humans; Keratins; Transplantation, Heterologous; Vimentin

The current medical treatment of endometriosis, a common gynaecological disease, is still associated with a high recurrence rate. To establish an appropriate in-vivo model to evaluate new therapeutic strategies we validated the nude mouse model for the intraperitoneal cultivation of human endometrial tissue.. Human endometrium of the proliferative phase was implanted into the peritoneal cavity of normal cycling and ovariectomized athymic mice and of cycling non-obese diabetic (NOD)-severe combined immuno-deficiency (SCID) mice. Morphology, proliferation, differentiation, and angiogenesis in the ectopic endometrium at different time points after implantation was investigated.. Adhesion of endometrial fragments was observed from day 2 onwards. The lesions persisted for up to 28 days revealing a well preserved glandular morphology. The glandular epithelium maintained cytokeratin expression even after 14 days of culture. With progressing culture, glands exhibited vimentin staining in combination with a decrease of surrounding stromal cells. Proliferation of glandular epithelium could be demonstrated throughout the investigated period of 28 days, whereas expression of oestrogen and progesterone receptors was maintained only in endometriotic lesions grown in cycling but not in ovariectomized mice. Neoangiogenesis occurred from day 4 onwards, independent from the intraperitoneal localization of the ectopic lesions.. This in-vivo model is a promising tool to test the effect of compounds such as different hormone agonists/antagonists or anti-angiogenic factors to develop new therapeutic concepts in endometriosis.

Topics: Adult; Animals; Cell Differentiation; Cell Division; Disease Models, Animal; Endometriosis; Endometrium; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mice; Mice, Inbred NOD; Mice, Nude; Mice, SCID; Neovascularization, Pathologic; Ovariectomy; Peritoneal Diseases; Premenopause; Receptors, Estrogen; Receptors, Progesterone; Tissue Adhesions; Vimentin

The purpose of this study was to validate the suitability of the severe combined immunodeficient (SCID) mouse as an experimental model for endometriosis, by defining the morphological and histological features of induced endometrial implants, and characterizing specific biochemical properties of these implants. Human secretory endometrial tissues were injected into the peritoneal cavity of SCID/SCID CB17 mature female mice. Successful peritoneal implantation was observed in 55 of 57 (96.5%) SCID mice and consisted of circumscribed elevated nodules. Haematoxylin-eosin staining of implanting lesions demonstrated the presence of endometrial glandular tissue in a mixed background of stromal and inflammatory cells. When progesterone was administered to mice, epithelial glands underwent well-defined secretory changes. Immunohistochemical analysis using polyclonal human pan-cytokeratin antibodies demonstrated selective positive staining in the glandular epithelium of the human implants with none in the surrounding stroma. In-situ hybridization analysis using complement component 3 cDNA radiolabelled riboprobes yielded significantly more intense signals in glands compared to stroma. As human endometrial implants in SCID mice were shown to retain specific histological, functional and biochemical properties, we conclude that the SCID mouse is an attractive animal model for the study of endometriosis.

Topics: Animals; Complement C3; Disease Models, Animal; Endometriosis; Endometrium; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Mice; Mice, SCID; Peritoneum; Transplantation, Heterologous; Transplantation, Heterotopic

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

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

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

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

While undergoing a repeat Caesarian section, a 21-year-old woman was found to have a subcutaneous, 3.5-cm tumor-like lesion in the abdominal wall. It had a lobulated contour and consisted of gelatinous tan nodules with intervening fibrous septa. It had a composite histology, including a solid pattern of large glassy cells with a predominant perivascular and pericystic/cisternal topography (35% surface area); a pattern of dyscohesive, vacuolated cells including physaliphorous-like forms (35% surface area); and a myxoid pattern of spindle to stellate cells showing frequent cell contact and lying within an optically clear or pale eosinophilic and bubbly extracellular matrix with a prominent capillary framework. A strong and diffuse cytoplasmic expression of vimentin (only) was present in all cytoarchitectural patterns. The extracellular matrix and intracytoplasmic vacuoles contained abundant acid mucosubstance, mostly hyaluronic acid. No distinct endometrial gland, stigma of hemorrhage, or nuclear estrogen/progesterone receptor protein expression was observed. There were variously sized and shaped cystic spaces lined by a flat to cuboidal cytokeratin-positive cell lining and focally containing neutral and acid mucosubstance. These spaces are interpreted as dilated endometrial glands rather than mechanically entrapped inclusions of mesothelial origin. In this setting, florid decidual reaction represents a potential diagnostic pitfall because it could be confused with more commonly encountered myxoid or epithelioid tumors of mesenchymal, epithelial, or melanocytic cell lineage.

Topics: Abdominal Neoplasms; Adult; Biomarkers, Tumor; Diagnosis, Differential; Embryo Implantation; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Sarcoma

Ten cases of endometriosis of bowel, ovaries, uterine serosa and 10 cases of adenomyosis were studied. Blocks of tissue with areas of interest were submitted for serial sectioning of the entire block. Some sections were immunostained for oestrogen receptor, vimentin, Ber-EP-4 and cytokeratins. The common finding was the presence of type 1 nodules, consisting of isolated nodules of endometrial stromal cells without endometrial glands, along blood or lymphatic vessels. The stromal cells showed positive immunoreactivities for oestrogen receptor and vimentin, and negative reactivities for cytokeratins. Due to the absence of connection with adjacent endometriosis or adenomyosis, it is likely that these endometrial stromal nodules arise from the multipotential pericytes. In addition, in serosa of all cases of endometriosis, type 2 nodules, having adjacent mesothelium (Ber-EP4-) changing into epithelium (Ber-EP4+) and type 3 nodules, with non-endometrial epithelium (oestrogen receptor-) changing into endometrial gland (oestrogen receptor+) were identified. We believe that the formation of type 1 nodules from the pericytes and the transformation of the mesothelium into endometrial glands in type 2 and 3 nodules are accomplished through the process of induction by the endometrial stroma, and the proliferation is controlled by genetic, hormonal and immunological factors. Type 1, 2 and 3 nodules are likely to represent a histological continuum in the development of early endometriosis. Subsequent to the formation of endometriosis in the serosa, the pathway of development of endometriosis and adenomyosis is similar. Through the processes of induction and proliferation there is an increase in size of the stroma of type 1 nodules and that of endometrial tissue with subsequent fusion of the stroma of type 1 nodules and that of foci of adenomyosis or endometriosis. Consequently, there is enlargement of the stroma of the foci of adenomyosis or endometriosis. The 'newly enlarged stroma' serves as 'new soil' for further growth of the endometrial glands in the endometrial tissue.

Topics: Adult; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Receptors, Estrogen; Retrospective Studies; Stromal Cells; Vimentin

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

To evaluate quantitatively cytokeratin and vimentin staining in glandular and stromal cells of eutopic and ectopic endometrium.. The investigation of cytokeratin and vimentin was carried out using the new computerized technology of image analysis.. University Hospital, Department of Gynecology.. Biopsies were taken from patients undergoing a laparoscopy for infertility (29 endometrial biopsies and 31 biopsies of peritoneal endometriosis). None of them were treated.. Cyclic variations of cytokeratin and vimentin staining were noted in eutopic endometrium. The cytokeratin and vimentin staining pattern consistently was lower in ectopic endometrium than in eutopic endometrium.. Endometriotic epithelial and stromal cells undergo a complex program of differentiation giving them histochemical characteristics similar to those observed in endometrium. Such a concomitant expression of antigenicity indicates their close relationship with their mesodermal müllerian origin.

Topics: Adult; Endometriosis; Endometrium; Female; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Menstrual Cycle; Reference Values; Staining and Labeling; Vimentin

Our purpose was to examine the immunohistochemical properties of epithelial cells in peritoneal fluid and to compare the staining characteristics with cells of endometrium, menstrual effluent, peritoneum, and endometriotic lesions.. Samples of menstrual effluent, endometrium, and peritoneal fluid and biopsy specimens of endometriotic lesions and peritoneum from 16 patients were examined. Monoclonal antibodies against vimentin, cytokeratin 18 and 19, and the monoclonal antibody BW495/36, staining an epithelial marker present in endometrium and absent in peritoneal epithelium, were used.. All but one sample of menstrual effluent and peritoneal fluid cells stained positively with antibodies against vimentin and cytokeratin 18 and 19. BW495/36 stained 14 of 16 menstrual effluent samples and nine of 16 peritoneal fluid cell samples. Endometriotic specimens showed staining with all markers. No major differences in staining properties were observed in menstrual effluent, endometrium, and peritoneal fluid cells between patients with or without endometriosis.. These results support the contention of transport of menstrual detritus to the peritoneal cavity in women with patent fallopian tubes.

Topics: Ascitic Fluid; Endometriosis; Endometrium; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Menstruation; Peritoneum; 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

To identify and compare the pattern of polypeptide synthesis and release of endometriosis with that of the normal endometrium in culture.. Endometriosis and endometrial biopsy specimens were obtained from women presenting for a variety of diagnostic and therapeutic examinations. Specimens were cultured as isolated epithelial and stromal cells and tissue explants with L-[35S]methionine. De novo synthesized proteins were identified by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fluorography, and Western blot analysis.. Five major deviations in protein synthesis and secretion were noted when comparing endometriotic and endometrial culture media. Endometriosis synthesized and secreted two proteins of stromal cell origin that were not produced by normal endometrium: endometriosis protein group I (M(r) 40,000 to 55,000; pI 4.0 to 5.2) and endometriosis protein group II (M(r) 30,000 to 32,000; pI 7.0 to 9.0). Conversely, endometriosis lacked the ability to secrete or asynchronously secreted three groups of secretory phase endometrial proteins in culture: endometrial protein group I (M(r) 25,000 to 27,000; pI 4.5 to 5.5) and endometrial protein group II (M(r) 68,000 to 72,000; pI 3.0 to 3.2) were endometrial epithelial cell products whereas endometrial protein group III (M(r) 70,000; pI 5.7) was of endometrial stromal cell origin.. Unique characteristics in endometriosis protein synthesis and secretion as compared with the endometrium indicate biochemical dissimilarities between these tissues, which may be used to develop diagnostic markers and gain insight into the etiology and/or pathophysiology of the disease.

Topics: Autoradiography; Biopsy; Cells, Cultured; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Endometriosis; Endometrium; Epithelium; Female; Humans; Keratins; Methionine; Molecular Weight; Organ Culture Techniques; Peptide Biosynthesis; Peptides; Protein Biosynthesis; Proteins; Sulfur Radioisotopes; Vimentin

Using a panel of 21 monoclonal and 2 polyclonal keratin antibodies, capable of detecting separately 11 subtypes of their epithelial intermediate filament proteins at the single cell level, we investigated keratin expression in 16 squamous cell carcinomas, 9 adenocarcinomas, and 3 adenosquamous carcinomas of the human uterine cervix. The keratin phenotype of the keratinizing squamous cell carcinoma was found to be most complex comprising keratins 4, 5, 6, 8, 13, 14, 16, 17, 18, 19, and usually keratin 10. The nonkeratinizing variety of the squamous cell carcinoma expressed keratins 6, 14, 17, and 19 in all cases, usually 4, 5, 7, 8, and 18, and sometimes keratins 10, 13, and 16. Adenocarcinomas displayed a less complex keratin expression pattern comprising keratins 7, 8, 17, 18, and 19, while keratin 14 was often present and keratins 4, 5, 10 and 13 were sporadically found in individual cells in a few cases. These keratin phenotypes may be useful in differential diagnostic considerations when distinguishing between keratinizing and nonkeratinizing carcinomas (using keratin 10, 13, and 16 antibodies), and also in the distinction between nonkeratinizing carcinomas and poorly differentiated adenocarcinomas, which do not express keratins 5 and 6. Keratin 17 may also be useful in distinguishing carcinomas of the cervix from those of the colon and also from mesotheliomas. Furthermore the presence of keratin 17 in a CIN I, II, or III lesion may indicate progressive potential while its absence could be indicative of a regressive behavior. Because most carcinomas express keratins 8, 14, 17, 18, and 19, we propose that this expression pattern reflects the origin of cervical cancer from a common progenitor cell, i.e., the endocervical reserve cell that has been shown to express keratins 5, 8, 14, 17, 18, and 19.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma; Carcinoma, Squamous Cell; Endometriosis; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Staining and Labeling; Uterine Cervical Neoplasms

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

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

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

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

Appropriate endometrial differentiation is believed to be a prerequisite for pregnancy success. This study investigates the expression of two intermediate filament proteins, cytokeratin and vimentin, in human endometrium and first trimester decidua and in ectopic endometrium from women with endometriosis. Stromal elements, including vascular endothelial cells, were consistently vimentin-positive and cytokeratin-negative. Surface and glandular epithelial cells of human endometrium co-expressed vimentin and cytokeratin during all stages of the menstrual cycle, but failed to express vimentin after the onset of pregnancy. This suggests that intermediate filaments, and especially vimentin, may have a role to play in the proliferation and/or differentiation of the endometrial glands during decidualization. Ectopic endometrium showed a staining pattern similar to normal endometrium.

Topics: Decidua; Endometriosis; Endometrium; Female; Humans; Keratins; Pregnancy; Pregnancy Trimester, First; Vimentin

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

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

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

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

We studied one case of atypical polypoid adenomyoma of the uerus immunohistochemically using antisera against keratins, vinentin, S-100 protein, desmin and actin. The stromal cells were reactive with anti-actin and antidesmin antibodies suggesting a muscular phenotype and confirming previous ultrastructural data. Immunohistochemical investigations have proved to be useful in differential diagnosis of APA with invasive adenocarcinoma, adenosarcoma and adenofibroma of the endometrium.

Topics: Actins; Adenocarcinoma; Adenofibroma; Desmin; Diagnosis, Differential; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; S100 Proteins; Uterine Neoplasms; Vimentin

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

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

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

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

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Nucleus; Chromatin; Cytoplasmic Granules; Desmosomes; Endometriosis; Endometrium; Female; Humans; Hyalin; Keratins; Microscopy, Electron; Middle Aged; Uterine Neoplasms