Primary mucinous adenocarcinoma of the renal pelvis with carcinoma in situ in the ureter

Primary epithelial tumor of the renal pelvis is rare and only 100 cases are reported in the literature [1]. Histological examination of the tumor showed glands, cysts, and papillae lined by pseudostratified columnar epithelium with hyperchromatic nuclei. Scattered signet ring-type cells were also seen floating in large pools of extracellular mucin. Sections from the ureter showed a component of adenocarcinoma in situ. No invasive tumor was identified in ureteric tissue. One case was reported with carcinoma in situ of the ureter (2).Immunohistochemically: The tumor showed positivity for CK7, CK20, CK8/18, GATA-3, MSH-2, MSH-6, MLH-1, Ber-EP4, and S-100-P with focal positivity for CDX-2, weak positivity for PMS-2 and negativity in TTF-1 and Her-2. Molecular pathological analysis revealed microsatellite stability and without mutation in K-ras-gene. Thus, a diagnosis of mucinous adenocarcinoma of the renal pelvis with in situ adenocarcinoma of the ureter was made.     

Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations

The authors report three cases of sarcomatoid carcinoma arising in the stomach. This uncommon tumor is characterized by a mixture of malignant epithelial and spindle cell elements. All three tumors were large (average diameter, 5 cm) and infiltrated deep into the stomach wall. Two of the tumors had a polypoid configuration; the third was ulcerated and endophytic. Intestinal metaplasia was present adjacent to the tumor in all cases, with dysplasia in two. Immunohistochemical studies showed positivity for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen in the epithelial component of all tumors, and Leu-M1 was positive in the epithelial component of one. The spindle cell components contained vimentin, and in tumor 2, the spindle cell component was also positive for desmin. Two tumors showed focal positivity for cytokeratin in the spindle cells immediately adjacent to the epithelial component. Ultrastructurally, the spindle cell component of two tumors was composed of undifferentiated cells without specific epithelial or mesenchymal features. The third tumor contained occasional cells with features of myofibroblasts.     

Spindle cell carcinoma of the penis--a case report

Over a 2-month period, a 34-year old man with phimosis developed a pedunculated tumor, measuring 4 X 2.5 X 2 cm in his glans penis. Microscopically the bulk of the tumor was composed of spindle-shaped cells, however, at some parts of the tumor, squamous cell cysts or nests, consistent with well-differentiated squamous cell carcinoma, were noted. Atypical epithelial cells merged imperceptibly with the underlying spindle-shaped cells. The histological diagnosis of spindle cell carcinoma, an uncommon variant of squamous cell carcinoma, was made. Spindle cell carcinoma arising from the penis is very rare and only two reports are available at present.     

Ultrastructural comparison of hepatoblastoma and hepatocellular carcinoma.

The ultrastructural characteristics of fetal liver, two hepatoblastomas and two hepatocellular carcinomas were compared. Tumor cells of hepatoblastoma disclosed monotonous nuclei, poorly-developed cytoplasmic membrane system, abundant free ribosomes and prominent glycogen granules. Thos of hepatocellular carcinoma revealed comparatively pleomorphic nuclei, well-developed cytoplasmic membrane system, a few free ribosomes and numerous glycogen granules. Fetal liver showed monotonous nuclei, well-developed RER abundant free ribosomes and prominent glycogen granules. Young mesenchymal cells with well-developed RER and continuous basal lamina surrounding the epithelial cells were detected in both cases of hepatoblastoma but not in those of hepatocellular carcinoma. Tumor cells of hepatoblastoma in a case showed intramitochondrial crystalloids and thick bundles of fibrils in the cytoplasm.     

Effect of a novel inhibitory mAb against beta-subunit of F1F0 ATPase on HCC

Hepatocellular carcinoma (HCC) represents a worldwide health problem. F1F0 ATPase, one of the most unique supermolecule enzymes in the inner mitochondrial membrane, was recently found located also on the plasma membrane of some tumor and epithelial cells. Ecto-F1F0 ATPase might play the major role in maintaining the normal average intracellular pH in those cells relative to tumor acidic extracellular microenviroment. Inhibiting the extracellular F1F0 ATPase on tumor exhibits both antiangiogenic and antitumorigenic activities. We found previously a strain of murine mAb, mAb6F2C4, which binds with beta-catalytic subunit of F1F0 ATPase. Immunofluorescence and flow cytometry assay showed that mAb6F2C4 could bind with plasma membrane of diverse hepatoma cells and HUVEC. Moreover, it could markedly block extracellular ATP generation of SMMC-7721 cells under extracellular acidic condition. In vitro, mAb6F2C4 retarded not only the proliferation and colony forming ability of SMMC-7721 cells, but also the proliferation and tube formation ability of HUVEC. mAb6F2C4 was located on plasma membrane of some hepatoma cells and attenuated dramaticly tumor growth in tumor xenograft models in nude mice. Therefore, we concluded that mAb6F2C4 binding with ecto-beta-subunit of F1F0 ATPase, could inhibit extracellular ATP synthesis and exhibit both antiangiogenic and antitumorigenic activities, which could be further developed for HCC therapy.     

Undifferentiated (embryonal) sarcoma of the liver. Epithelial features as shown by immunohistochemical analysis and electron microscopic examination

The cell differentiation properties of two undifferentiated (embryonal) sarcomas of the liver (USL), one in a 9-year-old boy and one in a 23-year-old man, were studied by immunohistochemistry and electron microscopic examination. Both tumors showed a part pleomorphic pattern and a part myxoid spindle cell sarcomatous pattern. An electron microscopic examination showed some tonofilament-like bundles of intermediate filaments and cell junctions in one case, suggesting the presence of epithelial differentiation in that tumor. An immunohistochemical analysis showed a large number of cytokeratin-positive neoplastic cells in both cases as studied with two different monoclonal antibodies, and most cells were positive for vimentin. No cells showed desmin, glial fibrillary acidic protein, or epithelial membrane antigen (EMA). Due to the presence of cytokeratin immunoreactivity, the possibility was considered that these tumors would represent anaplastic sarcomatoid variants of hepatocellular carcinoma. The tumor cells showed cytoplasmic alpha-1-antitrypsin (AAT) positivity, and were negative for alpha-fetoprotein. Because the immunoreactivity of AAT is widespread in different types of tumors, it is not possible to conclude that the AAT positivity would indicate the hepatoma nature of USL; however, this remains a possibility, especially when considering that in vitro transformed hepatocytes have been shown to be capable of forming sarcomatous tumors.     

鼻咽癌细胞系SUNE中EBV-LMP1基因对上皮细胞增殖的影响

目的研究鼻咽癌细胞系ＳＵＮＥ中ＥＢＶ┐ＬＭＰ１基因对上皮细胞增殖的影响,探索ＬＭＰ１在鼻咽癌发生中所起的作用。方法用ＬＭＰ１基因真核表达质粒转染人胚肾上皮细胞,检测ＬＭＰ１的表达,观察细胞在软琼脂中的集落形成能力,ＭＴＴ吸收能力以及ＰＣＮＡ的表达情况。结果被ＬＭＰ１基因转染的细胞生长旺盛,能在软琼脂中形成多个集落,ＭＴＴ吸收能力增强,ＰＣＮＡ的表达水平增高。结论ＬＭＰ１基因能明显改变上皮细胞的生物学行为,促进细胞的生长、增殖和转化,使转染的上皮细胞获得肿瘤细胞的生长特征。     

The distribution of epithelial membrane antigen in thymic epithelial neoplasms.

Thymic carcinomas arising within a thymoma have been reported, but the relationship between thymoma and thymic carcinoma is poorly understood. Epithelial membrane antigen (EMA) is known to be an effective marker for establishing the epithelial nature of neoplastic cells, and it is reported that staining of tumors is clearly related to the degree of tumor differentiation. Eighty-one thymomas (59 noninvasive, 22 invasive) and 14 thymic carcinomas were studied immunohistologically using antiepithelial membrane antigen (anti-EMA) monoclonal antibody. Thymic carcinomas tended to express much larger quantities of EMA than thymomas, and instances of EMA-positive thymoma were seen significantly more often in invasive thymomas than in noninvasive ones (P < 0.05). However, EMA positivity was also associated with gland-like structures, which were not necessarily associated with malignant disease. Nevertheless, in view of the concept that thymoma and thymic carcinoma show a similar cellular differentiation, EMA-positive epithelial cells in thymoma with no relation to gland-like configurations might represent a pool of cells having a latent potential for malignant disease and might be transformed into thymic carcinoma cells under certain conditions. Immunolabeling for EMA appears to be a useful tool for determining the degree of malignant disease among thymic epithelial neoplasms.     

Secretion of extracellular matrix-degrading proteinases is increased in epithelial ovarian carcinoma

The biochemical events associated with tumor invasion involve localized degradation of the basement membrane by tumor-associated proteinases. In this study, we have characterized the proteinase secretion profiles of 5 ovarian epithelial carcinoma cell lines (DOV 13, OVCA 420, OVCA 429, OVCA 432, OVCA 433) as well as normal ovarian epithelial cells. Immunocapture assays demonstrated that all 5 carcinoma cell lines produce both secreted and surface-associated plasminogen activator. Urinary-type plasminogen activator (u-PA) production was one order of magnitude greater than production of tissue-type plasminogen activator (t-PA). Furthermore, t-PA secretion by normal ovarian epithelial cells was not detectable, whereas u-PA production was 17-to 38-fold lower than in ovarian carcinoma cells. Western-blotting analysis demonstrated that u-PA was secreted as the single chain form (scu-PA) when cells were cultured in serum-free medium. Incubation of plasminogen with ovarian carcinoma cell-conditioned medium resulted in direct activation of the Zymogen to plasmin. Furthermore, following incubation of cells with plasminogen, plasmin was eluted from the cell surface, indicating that ovarian carcinoma cells contain binding sites for plasminogen/plasmin which are accessible to surface-associated plasminogen activators. In addition to plasminogen activators, metalloproteinases were also produced by DOV 13, OVCA 429 and OVCA 433 cells. DOV 13 cells produce a 68-kDa metalloproteinase similar to matrix metalloproteinase 2 (MMP-2) whereas a 92-kDa enzyme similar to MMP-9 is secreted by OVCA 429 and 433. Together, ovarian carcinoma-associated plasminogen activators and metalloproteinases catalyze the hydrolysis of the major basement membrane protein components, type-IV collagen, type-IV gelatin, laminin and fibronectin. The enhanced proteolytic capability of ovarian carcinoma cells relative to normal ovarian epithelium suggests a biochemical mechanism by which invasion and spread of ovarian epithelial carcinoma may be mediated.     

Inhibition of Ca(2+)-activated Cl(-) channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma

The etiology of prostatic adenocarcinoma remains unclear. Prostate cancer cells of varying metastatic potential and apoptotic resistance show altered expression of plasma membrane ion channels and unbalanced Ca(2+) homeostasis. Ca(2+)-activated Cl(-) channels (CaCCs) are robustly expressed in epithelial cells and function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis in proliferation, differentiation and apoptosis. ANO1/TMEM16A was recently identified as a CaCC, and it is of interest to determine whether ANO1 plays a role in development and metastasis of prostate carcinoma. Here we show that ANO1 mRNA and protein are highly expressed in human metastatic prostate cancer LNCaP and PC-3 cells by quantitative analysis of real-time PCR and Western blot. These findings were confirmed by whole-cell patch clamp recording of LNCaP and PC-3 cells with increased current density of ANO1 channels. Immunohistochemistry staining further revealed overexpression of ANO1 in human prostate cancer tissues, which correlated with the clinical TNM stage and Gleason score. Experiments with small hairpin RNAs (shRNAs) targeting human ANO1 resulted in a significant reduction of proliferation, metastasis and invasion of PC-3 cells using WST-8, colony formation, wound-healing and transwell assays. Moreover, intratumoral injection of ANO1 shRNA completely inhibited established tumor growth and survival in orthotopic nude mice implanted with PC-3 cells. Our findings provide compelling evidence that upregulation of CaCC ANO1 is involved in the proliferation, progression and pathogenesis of metastatic prostate cancer. Membrane ANO1 protein may therefore serve as a biomarker, and inhibition of overexpressed ANO1 has potential for use in prostate cancer therapy.     

Mucoepidermoid carcinoma of the thyroid gland.

An extremely rare case of mucoepidermoid carcinoma of the thyroid in a 56-year-old woman is presented. The patient clinically having Hashimoto's thyroiditis was noted a nodule in her neck. The tumor was sited in the midportion of the left lobe of the thyroid, and histologically it showed both squamous features and mucin production. The squamous cells were arranged in solid sheets with horny pearls and the mucous cells tended to line dilated duct-like elements. Ultrastructurally, the epidermoid cells had aggregates of tonofilaments and well-developed desmosomal attachments, and the mucous cells contained numerous mucin granules in their cytoplasm. Immunohistochemical studies revealed that cytokeratin antibodies showed positivity for both the lining cells and squamous cells, whereas carcinoembryonic antigen positivity was found in the lining cells and intraluminal material. The tumor cells were negative for thyroglobulin, calcitonin, vimentin, chromogranin, and neuron-specific enolase. These unusual histologic and immunohistochemical features are suggestive of a tumor related to the so-called "solid cell nest" of the thyroid.     

Epidermal growth factor receptor monoclonal antibody inhibits constitutive receptor phosphorylation, reduces autonomous growth, and sensitizes androgen-independent prostatic carcinoma cells to tumor necrosis factor alpha.

Results of recent studies indicate that cultured, androgen-independent prostatic carcinoma cells synthesize and secrete transforming growth factor alpha, which interacts with epidermal growth factor receptors (EGFRs) to promote autonomous growth. In the present study, we evaluated the expression and constitutive activation of EGFRs in normal prostatic epithelial cells and the androgen-independent prostatic carcinoma cell lines PC3 and DU145. Our studies showed that cultured normal epithelial cells and androgen-independent prostatic carcinoma cells actively synthesize and exhibit constitutive phosphorylation of the M(r) 170,000 EGFR. The addition of monoclonal anti-EGFR reduced receptor phosphorylation and significantly inhibited the proliferation of prostatic tumor cells. The observed reduction in EGFR phosphorylation could be partially attributed to an antibody-induced decrease in the expression of metabolically labeled EGFR. Results of further studies showed that anti-EGFR enhanced the sensitivity of PC3 cells to the cytotoxic and cytostatic effects of tumor necrosis factor alpha. These studies demonstrate that constitutive activation of EGFR in androgen-independent prostatic carcinoma plays a functional role in the regulation of cellular proliferation in vitro. In addition, the enhanced sensitivity of prostatic carcinoma cells to tumor necrosis factor alpha in the presence of anti-EGFR provides a rationale for the further investigation of combination therapy in the treatment of disseminated, androgen-independent disease.     

Inhibition of proliferation, VEGF secretion of human neuroendocrine tumor cell line NCI-H727 by an antagonist of growth hormone-releasing hormone (GH-RH) in vitro

Growth hormone-releasing hormone (GH-RH) can stimulate not only growth hormone (GH) secretion by anterior pituitary gland but also proliferation of many cancer cell lines in vitro and in xenografts tumor models in vivo. Several antagonists of GH-RH have been shown to inhibit several cancer growths, but the role of GH-RH antagonists in the regulation of neuroendocrine cancers cell proliferation and tumor progression remains obscure. The aim of the study was to evaluate the influence of JV-1-36 (synthetic GH-RH antagonist) on proliferation and VEGF secretion by human neuroendocrine lung non-small cell carcinoma (NCI-H727) using cell culture model. The in vitro effect of JV-1-36 on the proliferation of NCI-H727 cells was assessed by the measurement of BrdU incorporation by colorimetric immunoassay. The presence of VEGF and membrane GH-RH receptors on the surface of H727 cells were visualized by immunocytochemistry using specific anti-GH-RH receptor antibody directed to the carboxy-terminal region. VEGF secretion to the cell cultures supernatants was assessed by ELISA methods. Immunoreactive cell membrane GH-RH receptors and VEGF-immunopositive cytoplasmatic granules were clearly confined on the surface of nearly all cancer cells. JV-1-36 at the concentration of 10(-6)-10(-10)M significantly inhibited growth of H727 cells, compared with untreated controls. In H727 cells, the antiproliferative JV-1-36 effect was associated with a dose-dependent reduction of VEGF secretion. In conclusion, our findings demonstrate the strong evidence for the antiproliferative action of GH-RH antagonist JV-1-36 for the NCI-H727 cells. In addition the suppression of VEGF secretion by H727 cells might contribute, at least in part, to the antitumor action of GH-RH antagonists.     

Pleomorphic carcinoma of the gallbladder: report of a case.

The authors report a rare case of primary pleomorphic carcinoma of the gallbladder in a 70-year-old woman. A polypoid tumor protruded into the lumen from the fundus of the gallbladder. Characteristic histologic findings included a general lack of architectural cohesiveness, marked pleomorphism, presence of mononucleated and multinucleated giant cells, extensive necrosis, leukocyte-tumor cell phagocytosis or cannibalism. Immunoreactivity for cytokeratin, carcinoembryonic antigen and epithelial membrane antigen as well as histochemical positivity for mucins demonstrated the epithelial nature of the tumor. The neoplasm behaved aggressively; the patient died of metastases 9 months after the operation.     

Histiocytoid breast carcinoma: a case report with immunohistochemical and ultrastructural studies

This is the first documented report of a case of histiocytoid breast carcinoma in Japan. The patient was a 55-year-old woman with a right breast lump. An excisional biopsy revealed proliferation of histiocyte-like cells with slightly atypical nuclei within fibrous stroma. In places, tumor cells showed an invasive pattern similar to that in invasive lobular carcinoma including a targetoid pattern, as well as a focus of in situ lobular carcinoma with transition to the histiocytoid cells. Immunohistochemical stainings of the tumor cells demonstrated positive reactions for cytokeratins and epithelial membrane antigen. Gross cystic disease fluid protein 15, an apocrine marker, was almost uniformly positive in their cytoplasm. From these results, we supposed that histiocytoid breast carcinoma is a variant of invasive lobular carcinoma. Histiocytoid breast carcinoma is easily misdiagnosed as a benign lesion such as granular cell tumor or xanthoma. Points of differential diagnosis were described and we stressed that it is most important for pathologists to keep this variant in mind in order to avoid misdiagnosis.     

A polypoidal adenosquamous cell carcinoma of the esophagus with a pseudosarcomatous stromal reaction

A case of a polypoidal carcinoma with a pseudosarcomatous stromal reaction is presented. Histologically, the polypoidal tumor of the lower esophagus was revealed to be an adenosquamous cell carcinoma associated with the proliferation of atypical stromal cells, osteoclastic-like giant cells, and histiocytes. Using an immunohistochemical stain, these stromal atypical cells were found to be positive for vimentin, with some cells positive for alpha 1-antichymotrypsin. However these atypical cells proved negative as epithelial markers (keratin and EMA). Thus, it was felt that such atypical stromal cells may be a reactive proliferation of the stromal cells to an adenosquamous cell carcinoma.     

Chromogranin A-positive tumor cells in human esophageal squamous cell carcinomas

Gastrointestinal cancers have frequently shown neuroendocrine (NE) differentiation, but whether NE differentiation occurs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, tissue sections obtained from 43 patients with ESCC from a high-incidence area of Northern China were used for the assessing of NE differentiation by immunohistochemistry using antibody against chromogranin A (CGA). In addition, the malignant characteristics and proliferation capacity of CGA-positive cells were also examined by immunohistochemistry. The clinicopathological significance of these CGA-positive tumor cells in ESCC was assessed. Of 43 ESCC samples, CGAimmunoreactive tumor cells were detected in 10 cases (23.26%). However, the CGA-positive tumor cells were scattered at a very low number among non-immunoreactive tumor cells and were rarely constituted a major part of cancer cell nests. Only 4.65% (2/43) cases showed a high density (>10 cells but <1% of total tumor cell mass) of CGA-positive tumor cells. P53 immunoreactivity was frequently shown, while Ki67 was hard to detect in these CGApositive cells. In addition, no relationship between CGA positivity rate and clinicopathological parameters was found. Thus, we concluded that lowdensity CGA-positive tumor cells can be detected in ESCC, supporting the notion that heterogeneous NE differentiation also exists in tumors that lack neuroendocrine cells in their normal epithelial counterparts.     

Opsonization with a trifunctional bispecific (alphaCD3 x alphaEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes

Removab is a trifunctional bispecific antibody which can bridge CD3+ T cells and epithelial cell adhesion molecule positive (EpCAM+) tumor cells, and binds with its Fc fragment to antigen presenting cells. To explore a new approach for the treatment of patients with carcinoma of the upper aerodigestive tract, we investigated whether Removab can induce specific cellular responses to the EpCAM+ carcinoma cell line BHY. Particular emphasis was put on the opsonization of peripheral blood mononuclear cells (PBMN) with respect to clinical application. Tumor cells and allogeneic PBMN of healthy volunteers were incubated with or without Removab. In a third group, PBMN were opsonized with Removab and washed before incubation with tumor cells. Inverse microscopy, ELISPOT, flow cytometry analysis and cytotoxicity assays on the chorioallantois membrane (CAM) were performed. In comparison with PBMN alone, opsonization with Removab resulted in: a) activation of CD83+ antigen presenting cells, b) secretion of interferon gamma, and c) granzyme B mediated lysis of targeted BHY cells by EpCAM specific CD8+ T cells. The secretion of tumor necrosis factor alpha, interferon gamma and interleukin-2 by opsonized PBMN was significantly reduced after 24 h. Washed opsonized PBMN maintained their lytic activity against tumor cells as tested on the CAM. Removab is an appropriate agent for the therapeutic amplification of T cell responses against EpCAM+ tumor cells by opsonization of PBMN without putting patients at risk for severe adverse events caused by a cytokine storm.     

Duct-like morphogenesis of Longnecker pancreatic acinar carcinoma cells maintained in vitro on seminiferous tubular basement membranes

We have investigated the behavior of dissociated cells of a moderately differentiated Longnecker transplantable pancreatic acinar carcinoma (Longnecker et al., Cancer Lett., 7: 197-202, 1979) maintained in vitro on acellular seminiferous tubular basement membranes of rat testis. The tumor cells, which grow as solid masses in vivo with little organization, undergo organogenesis in vitro into distinct duct-like structures with lumina in the presence of basement membrane scaffoldings. These duct-like structures were formed by flattened epithelial cells, which exhibited poorly differentiated acinar cell characteristics with few or no zymogen (secretory) granules. The cells lining the duct-like structures retained the pancreatic acinar cell specific antigen as determined by indirect immunofluorescence. DNA synthesis did not accompany duct-like organization; however, all of the cells lining these structures continued to incorporate [3H]leucine for up to 4-5 days of culture. They continued to synthesize and secrete amylase, a marker protein of pancreatic acinar cells, into the medium. These results demonstrate that neoplastic epithelial cells of Longnecker pancreatic tumor differentiate into duct-like structures when they come into contact with a basement membrane scaffolding and do not accumulate well-formed secretory granules. This is in marked contrast to the previously reported in vitro differentiation of cells derived from another transplantable rat pancreatic acinar cell carcinoma where the neoplastic cells were fully cytodifferentiated on seminiferous tubular basement membrane without forming duct-like structures but accumulated abundant well-developed zymogen granules (Watanabe et al., Cancer Res., 44: 5361-5366, 1984). Although the basal lamina promotes differentiation of cells of two different pancreatic carcinomas in vitro, we conclude that the in vitro expression of morphogenetic and cytodifferentiation patterns is dependent upon the intrinsic properties of cells of these two transplantable pancreatic tumors.     

Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE) cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.