INCREASED EXPRESSION OF CYCLIN-DEPENDENT-KINASE-INHIBITOR-2 (CDKN2A) GENE-PRODUCT P16(INK4A) IN OVARIAN-CANCER IS ASSOCIATED WITH PROGRESSION AND UNFAVORABLE PROGNOSIS

Paraffin sections from 190 epithelial ovarian tumours, including 159 m alignant and 31 benign epithelial tumours, were analysed immunohistoch emically for expression of cyclin-dependent kinase inhibitor 2 (CDKN2A ) gene product p16(INK4A) (p16). Most benign tumours showed no p16 exp ression in the tumour cells, whereas only 11% of malignant cancers wer e p16 negative. A high proportion of pl6-positive tumour cells was ass ociated with advanced stage and grade, and with poor prognosis in canc er patients. For FIGO stage 1 tumours, a high proportion of pl6-positi ve tumour cells was associated with poorer survival, suggesting that a ccumulation of p16 is an early event of ovarian tumorigenesis. In cont rast to tumour cells, high expression of p16 in the surrounding stroma l cells was not associated with the stage and grade, but was associate d with longer survival. When all parameters were combined in a multiva riate analysis, high p16 expression in stromal cells was not an indepe ndent predictor for survival, indicating that low p16 expression in st romal cells is associated with other markers of tumour progression, Hi gh expression of p16 in the stromal cells of tumours from long-term su rvivors suggests that tumour growth is limited to some extent by facto rs associated with p16 expression in the matrix. (C) 1997 Wiley-Liss, Inc,.