Expression of cell cycle proteins in ovarian carcinoma cells in serous effusions-biological and prognostic implications

Objective. The aim of this study was to investigate the expression of cell cycle proteins in ovarian carcinoma cells in serous effusions and respectiv e solid tumors. Methods. Fifty-five malignant effusions and 38 tumors (20 primary, 18 metas tatic) were immunohistochemically stained for cyclin A, p27(kip1), and Ki-6 7. Staining extent (0-100% cells) and intensity (0-3 scale) were scored. Cy clin A and p27(kip1) expression was additionally studied in 29 malignant ef fusions using immunoblotting. Immunohistochemistry results in effusions wer e evaluated for possible association with clinicopathologic parameters. Results. Nuclear immunoreactivity for all markers was detected on carcinoma cells in the majority of effusions using immunohistochemistry. Similarly, immunoblotting showed the presence of cyclin A and p27(kip1) in 29/29 and 2 5/29 specimens, respectively. Intense (3) immunoreactivity for Ki-67 was de tected more often in peritoneal effusions, compared with those of pleural l ocation (P = 0.036). Staining in primary and metastatic lesions was general ly comparable to that of tumor cells in effusions. Staining for p27(kip1) w as more diffuse in effusion specimens obtained prior to the institution of chemotherapy (P = 0.042). In an analysis of all effusions, an association w as observed between the number of cells that were immunoreactive for Ki-67, cyclin A, and p27(kip1) (cyclin A-Ki-67: P = 0.008; p27(kip1)-Ki-67: P = 0 .019; cyclin A-p27(kip1): P = 0.032). In survival analysis, the presence of more diffuse (P = 0.042) and intense (P = 0.019) staining for cyclin A cor related with prolonged overall survival. Conclusions. The expression of the studied cell cycle markers does not diff er markedly between ovarian carcinoma cells in the pleural and peritoneal c avity, supporting our previous studies of several metastasis-associated mol ecules. The presence of cyclin-A-positive cell populations is associated wi th a more favorable disease outcome, possibly due to the targeting of proli ferating cells by chemotherapeutic agents. However, the decline in the frac tion of p27(kip1)-positive cells in posttreatment specimens may point to ad ditional mechanisms involved in this selection. (C) 2001 Academic Press.