Low‐molecular weight forms of cyclin E differentiate ovarian carcinoma from cells of mesothelial origin and are associated with poor survival in ovarian carcinoma

BACKGROUND. The authors recently reported on the role of cyclin E in differentiating ovarian/primary peritoneal carcinoma from malignant peritoneal mesothelioma using gene expression arrays. In the current study, they analyzed the expression of low‐molecular weight (LMW) forms of cyclin E in ovarian carcinoma, malignant mesothelioma, and benign reactive effusions. METHODS. Cyclin E protein expression was analyzed in 98 effusions (72 ovarian carcinomas, 14 malignant mesotheliomas, and 12 reactive specimens) using immunoblotting. Sixty‐two ovarian carcinoma effusions were studied further for cyclin E expression using immunohistochemistry. The correlations between cyclin E expression in ovarian carcinoma and clinical parameters, including chemotherapy response, were analyzed. RESULTS. LMW forms of cyclin E were identified in 54 of 72 ovarian carcinoma effusions (75%) compared with 1 of 14 malignant mesothelioma effusions (7%) and 1 of 12 reactive effusions (8%) ( P < .001). Their presence in ovarian carcinoma was associated with a higher percentage of cyclin E‐positive cells ( P = .001) and increased staining intensity ( P < .001) using immunohistochemistry. The presence of LMW forms of cyclin E was correlated with shorter overall survival ( P = .021) and progression‐free survival ( P = .020). The presence of a higher percentage of cyclin E‐positive cells using immunohistochemistry was correlated with shorter progression‐free survival ( P = .026). No association with chemotherapy response was observed. CONCLUSIONS. LMW forms of cyclin E differentiated ovarian carcinoma from benign and malignant mesothelial cells and were associated with increased protein expression using immunohistochemistry. The expression of LMW cyclin E forms was not associated with chemotherapy response, although it may be a marker of aggressive disease in patients with metastatic ovarian carcinoma. Cancer 2007. © 2007 American Cancer Society.