IDENTIFICATION OF ALLELIC LOSSES IN BENIGN, BORDERLINE, AND INVASIVE EPITHELIAL OVARIAN-TUMORS AND CORRELATION WITH CLINICAL OUTCOME

BACKGROUND, The somatogenetic alterations that lead to the development of benign adenomas, borderline tumors, and invasive ovarian carcinoma s are not well understood. This study investigated allelic losses in t hese three types of ovarian tumors. METHODS, Twelve genetic regions on chromosomes 2q, 5q, 6p, 6q, 9p, 11q, 17p, 17q, 18q and 22q were analy zed by polymerase chain reaction for loss of heterozygosity (LOH). The study was performed on formalin fixed, paraffin embedded tissue sampl es from 72 invasive ovarian carcinomas, 35 ovarian tumors of borderlin e malignancy, and 25 benign ovarian adenomas. RESULTS. LOH was found i n only 8% of the analyzed adenomas (at 2q21 and 17p13) and 11% of the borderline tumors (at 2q21, 5q21, 6p21, 17p13, and 17q21). Allelic los ses were noted for 77.7% of all of the invasive carcinomas analyzed. T he frequency of LOH was 56% at a locus near 17p13 (TP53) and 40.5% at 17q21 (BRCA1). LOH was observed in 30.4% of informative cases at 5q21 and in 21.4% at chromosome 18q21. The chromosomal regions 2q21-22 and 9p21 had deletions at frequencies of 32.4% and 25%, respectively. Inte rnational Federation of Gynecology and Obstetrics stage and the presen ce of LOH correlated significantly with survival but were not independ ent predictors of survival. Serous subtypes of invasive carcinoma were significantly more prone to deletions than nonserous tumors. CONCLUSI ONS, The results of this study suggest that LOH occurs only occasional ly in adenomas and borderline tumors, whereas it is frequently observe d in invasive ovarian carcinomas. Therefore, other genetic events seem to be involved in early ovarian tumor development. However, the prese nce of multiple allelic losses is an indicator of higher stages of inv asive carcinoma. (C) 1997 American Cancer Society.