CONCURRENT ABNORMAL EXPRESSION OF ERBB-2, MYC AND RAS GENES IS ASSOCIATED WITH POOR OUTCOME OF OVARIAN-CANCER PATIENTS

Epithelial ovarian cancer probably occurs due to activation of several different combinations of genes, which produce cancers that vary biol ogically and clinically. We tested this hypothesis in 100 consecutive ovarian carcinomas by molecular biology techniques at the DNA and prot ein levels in three genes (erbB-2, myc, ras), which are frequently alt ered in this tumor system. Abnormally high expression of erbB-2 gene e ncoded p185 protein was observed in 31% of the samples, while erbB-2 g ene amplification was detected by Southern analysis in 8%. ErbB-2 abno rmal gene expression did not significantly affect the clinical outcome of patients, conferring a marginal worsening of survival. In 25 out o f 96 (26%) tumor samples there was myc amplification. Higher levels of the ras-encoded p21 protein than in normal ovaries and benign ovarian tumors were found in 45% of the samples. Simultaneous overexpression of p185 and p21 was associated with shorter disease free (p = 0.02) an d overall survival (p = 0.04) at significance levels notable higher th an those observed for these oncoproteins singly. In addition, survival of patients with myc amplification and high p185/p21 coexpression was significantly worse (p<0.05) than that of patients with normal levels . Our data suggest that concurrent abnormal gene expression may act sy nergistically to endow ovarian tumor cells with a highly aggressive ph enotype. Evaluation of these genes may be helpful in the biological ch aracterization of ovarian cancer and in defining individual patient pr ognosis.