P16INK4a expression in cytology of ascites and response to chemotherapy in advanced ovarian cancer

Abstract

The aim of this study is to investigate p16INK4a expression by immunocytochemistry for ascites in advanced ovarian cancer and explore the possibility to predict chemotherapeutic response and prognosis. The immunocytochemical study was performed on cytology of ascites obtained from 37 Stage III or Stage IV ovarian cancer patients with measurable disease before platinum/taxane-based first-line chemotherapy following primary cytoreductive surgery or as neoadjuvant chemotherapy. Twenty-one of 21 (100%) responders and 6 of 16 (44%) nonresponders showed p16INK4a immunopositivity (p < 0.001). Immunopositivity was frequently observed in serous adenocarciomas (17 of 18, 94%). Overall survival was significantly better in immunopositive cases compared with immunonegative cases (p = 0.0006). For subcellular localization, cytoplasm was diffusely positive in immunopositive cases (n = 27), 12 of which showed stronger nuclear immunostaining and demonstrated superior overall survival. In vitro expression of p16INK4a protein was also examined for both parent chemosensitive and acquired chemoresistant ovarian cancer cell lines. Chemosensitive KF28 parent cells showed stronger nuclear staining compared with chemoresistant KFr13Tx cells showing stronger cytoplasmic staining by immunocytochemistry, which were also confirmed by western blotting. Our data suggest that p16INK4a expression in cytology of ascites is a candidate marker in prediction of the primary response to chemotherapy and prognosis.