Evaluation of novel prognostic factors In ovarian carcinoma

Abstract

Clinical information was collected from 283 randomly chosen ovarian cancer cases from at the Saskatoon Cancer Centre between the years 1983-1995. The data was evaluated for its significance in predicting survival and relapse free survival (RFS) using univariate and multivariate analysis. Several clinical prognostic factors were identified by univariate analysis. Additionally, using Cox's regression model the independent markers of survival and RFS were FIGO stage, and residual disease in 173 and 178 patients respectively. Data on CA 125 serum level, (available in 89 patients) was a marker of prognostic significance in the patients treated with platinum based chemotherapy. CA 125 and CEA antigen expression were also evaluated in seventy one cases. It was found that mucinous neoplasms exclusively expressed CEA antigen. This study indicates that the evaluation of serum level CEA may be a complementary tool for patients with cancers not expressing CA 125. In this retrospective study, DNA from paraffin embedded tissue (PET) in patients with ovarian carcinoma was examined to identify gene abnormalities in p53, p16INK4A, RB-1, p21WAF1/CIP1, Cyclin D1, Erb-B2, and MSH2. Adverse outcome was also examined in addition to survival and RFS, to identify novel molecular prognostic markers. P53 overexpression in 44 of 112 (39%) was associated with reduced survival and RFS (' p' = '0.04' and 'p' = '0.008 '). Aneuploid DNA content, found in 34 of 112 (30%) cases, was associated with shorter survival and RFS ('p' = '0.03' and 'p' = '0.01'). Dot blot hybridization of G1-S control genes (p16INK4A, Cyclin D1, RB-1, and CDK4) did not identify amplification or deletion events to be associated with adverse outcome. A number of gene alterations in 59 of 63 (94%) ovarian cancer cases were detected by dot blot hybridization; the lack of association with clinical outcome indicated that there may be some other genes in addition to those examined that are of prognostic significance. For eighteen cases, microsatellite instability (MSI) was evaluated by using fluorescently labeled primers at nine loci. LOH was a common event in ovarian carcinoma but MSI was infrequent. Molecular and clinical marker multivariate analysis indicated: (a) residual disease for survival, (b) stage and residual disease for RFS, were independent markers of prognosis.