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Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. Intraoperative staging at the primary surgery depends in part on the results of peritoneal wash cytology. However, peritoneal wash specimens may only show subtle cytologic changes that are indeterminate for the diagnosis. Thus, it is important to identify more accurate methods for cancer detection in pelvic wash cytology specimens to assist the clinical management of patients with ovarian cancer. We have previously shown that B7-H4 (DD-O110), a cell surface glycoprotein, is overexpressed in most non-mucinous ovarian carcinomas has little or no expression in most normal tissues. In the current study, we compared the detection of B7-H4 with that of calretinin, and pancytokeratin as diagnostic markers of ovarian cancer in peritoneal wash cell block preparations. Archival formalin-fixed blocks of peritoneal wash that were collected at the time of initial surgical resection of the primary tumors were identified in the UC-HSC Pathology Departmental Database. Sections of the cell blocks and corresponding representative sections of the primary tumors were stained by indirect immunoperoxidase methods, using a proprietary mouse monoclonal antibody to B7-H4 and commercially-obtained antibodies to calretinin and pancytokeratin. Cases were scored for the proportion of positive staining of epithelioid cells. Correlation among staining in cell block sections, staining in primary tumor sections, cytologic and histologic diagnosis, and pathologic stage was determined. B7-H4 staining was only detected in cytologically equivocal or malignant cells and was never observed in mesothelial cells, or other benign cell populations. By contrast, calretinin staining showed patchy staining of mesothelial cells but was negative in cytologically malignant cells, while pan-cytokeratin was detected in both mesothelial cells and in tumor cells. Cytoplasmic and membranous B7-H4 staining was detected in 20/21 cases with positive cytologic diagnosis; in 7/11 cases that were cytologically equivocal for carcinoma, and in 0/31 cases that had negative cytologic diagnosis. The sensitivity of the cytology alone, compared to the final diagnosis of peritoneal surface involvement by cancer cells, was 45%, with a specificity of 100%. The combination of conventional cytology with the B7-H4 testing increased the overall sensitivity of cytologic staging to 61% with 100% specificity. Thus, B7-H4 immunocytochemistry resulted in an overall 35% increase in the sensitivity of detection of tumor cells in pelvic wash cytology. These results indicate that B7-H4 could be a powerful diagnostic adjunct to improve the accuracy of staging of ovarian cancer cases.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]