The Expression And Clinical Significance Of Villin, CDX-2, CK7, And CK20 In Primary And Metastatic Ovarian Epithelial Carcinoma Tissue

Bankground and SubjectivePrimary ovarian carcinoma is a common gynecologic cancer. The ovary is a common site of metastatic tumour. Epithelial tumors account for slightly more than half of all ovarian tumors and 90% of all ovarian cancers. It is reported that approximately 7% to 17% of malignant tumors involving the ovary are metastatic ovarian carcinoma. The most common tumors that metastasize to the ovary arise in the colorectum, breast, endometrium, stomach, cervix, pancreas, appendix, and biliary tract. On routine microscopic examination, metastatic adenocarcinoma, particularly of gastrointestinal origin, may so closely mimic a primary ovarian adenocarcinoma that the correct diagnosis can be overlooked. Similarly, up to 45% of metastases from the colon are clinically interpreted as primary ovarian carcinoma. Arriving at the correct diagnosis is obviously important that the prognosis and management of a primary ovarian tumor are often significantly different from those of a metastatic neoplasm. Colorectal cancer is generally treated with 5-FU; ovarian cancer is generally treated with paclitaxel and a platinum agent. In many cases there is a known history of a primary neoplasm but on occasions presentation is with symptoms related to an ovarian mass in a patient with no known history of malignancy. In such cases, the primary neoplasm may not manifest itself until some time later. Carcinoma of unknown primary has a badly prognosis, with a median survival of 4-5months, and the tumors tend to respond poorly to empirical therapy.A number of markers have been used in an attempt to distinguish colon and ovarian malignancies by immunohistochemistry. The combined expression profiles of CK7 and CK20, is already an established parameter in the differential diagnosis of ovarian primaries from metastatic carcinoma to the ovary, but none of the markers is fully site specific .so there is still a clear need for additional markers. The two best candidates identified were Villin and CDX-2 for colon cancer cells. Villin is a cytoskeletal protein required for the formation of brush border microvilli in the normal small intestine, colon, pancreatic ducts, biliary system, and proximal renal convoluted tubules. The restricted tissue expression of Villin is conserved during neoplastic processes and an apical or brush border pattern of Villin expression is seen in all gastrointestinal adenocarcinomas. The caudal-related CDX-2 gene encodes an intestine-specific transcription factor belonging to the homeobox family that plays an important role in the regulation of proliferation and differentiation of intestinal epithelial cells. CDX-2 is expressed in normal colonic epithelia and most colorectal adenocarcinomas.Immunohistochemical detection of Villin, CDX-2, CK7, and CK20 were performed on 45 cases of primary ovarian epithelia adenocarcinoma (18 cases of serous, 15 cases of mucinous, 12 cases of endometrioid), 15 cases of colonic carcinoma metastatic to the ovaries, 20 cases of primary colonic carcinoma and 10 cases of normal ovary tissue. We investigate the clinical significance of a limited panel consisting of Villin, CDX-2, CK7, and CK20 differentiating primary and metastatic ovarian tumor and provide the theorectical evidence of diagnosis and theropy for ovarian carcinomas.Materials and Methods1.All the specimens were obtained from the Department of Pathology of Zhengzhou University between January 2000 and December 2005. 45 cases of primary ovarian epithelia adenocarcinoma (18 cases of serous, 15 cases of mucinous, 12 cases of endometrioid), 15 cases of colonic carcinoma metastatic to the ovaries, 20 cases of primary colonic carcinoma and 10 cases of normal ovary tissue were retrieved. All the cases were based on well-refined clinicopathological criteria. The course of disease was 0.5 to 18.0 months (mean 9.5 months). There were no significant difference of ages in all patients (P >0.05).2. Immunohistochemical detection of Villin, CDX-2, CK7, and CK20 were performed on 45 cases of primary ovarian epithelia adenocarcinoma (18 cases of serous, 15 cases of mucinous, 12 cases of endometrioid), 15 cases of colonic carcinoma metastatic to the ovaries, 20 cases of primary colonic carcinoma and 10 cases of normal ovary tissue.3. Statistical analysis: The SPSS statistical package program 10.0 was used for all analyses. Associations between the variables were tested by x~2 test and Fisher's exact test, P<0.05 were was considered statistically significant.Results1. Positive rates of Villin, CDX-2,CK7 and CK20 in ovary primary epithelia carcinoma were 8.8%(4/45),6.7%(3/45), 95.6%(43/45), 33.3% (15/45) respectively; the positive rates in Metastatic ovarian carcinoma tissue were 100%(15/15), 100%(15/15), 13.3%(2/15), 86.7%(13/15) respectively; the positive rates in colon primary tumor Tissue were 100% (20/20), 100%(20/20), 20%(4/20), 90%( 18/20) respectively. The positive expression rates of CK7 was 10%(1/10) in normal ovary tissues. There was no positive expression of Villin, CDX-2, and CK20 in normal ovary tissues (0/10). The expression rates of Villin, CDX-2, and CK20 were higher in colonic carcinoma metastatic to the ovaries than ovary primary carcinoma (P<0.001). The expression rates of CK7 was higher in the ovary carcinoma tissue than normal ovary tissue and colonic carcinoma metastatic to the ovaries (P<0.001). There were no significant differences of expression rates of Villin, CDX-2, CK7, and CK20 between colonic carcinoma metastatic to the ovaries and colon primary carcinoma (P >0.05). There were no significant diferences of expression rates of Villin and CDX-2 in all tissues (P>0.05).2. The positive expression rate of CK20 was higher than that of Villin and CDX-2 in primary ovarian tumor tissue (P <0.05). There was no positive expression of Villin and CDX-2 in ovary primary serous and endometrioid carcinoma.Conclusions1 .The high expression of Villin and CDX-2 in colonic carcinoma metastatic to the ovary and The low expression of them in primary ovarian epithelia carcinoma suggest they are the markers in differentiating primary and metastatic ovarian carcinoma. Villin and CDX-2 are more specific than CK20 as they are lower expression in primary ovarian carcinoma. 2. The high expression of CK7 suggest the tumor is primary ovarian carcinoma.