A CASE-MATCHED MOLECULAR COMPARISON OF EXTRAOVARIAN VERSUS PRIMARY OVARIAN ADENOCARCINOMA

BACKGROUND. Extraovarian mullerian adenocarcinoma (EOM) resembles prim ary ovarian carcinoma (POC) both histologically and clinically, yet li ttle is known regarding the molecular genetic characteristics of this entity. The objective of this study was to compare the expression of t hree molecular markers of tumor behavior in EOMs and POCs. METHODS. Fo rty-four patients meeting strict criteria for EOM were identified and matched to POC controls for age, stage, tumor histology and grade, cyt oreductive surgery, and survival. Immunohistochemistry was used to det ermine overexpression of p53 and HER-2/neu. DNA content was evaluated by now cytometry. Direct DNA sequencing of exons 5-8 of the p53 gene w as performed in nine EOM tumors. Statistical comparisons were made usi ng chi-square, Kaplan-Meier, and Mantel-Cox log rank methods. RESULTS. Overexpression of HER-2/neu was demonstrated in 59% (26 of 44) of the EOM group versus 36% overexpression (16 of 44) in the POC controls (P = 0.05). Overexpression of p53 was noted in 48% of the EOM cases, sim ilar to the 59% incidence observed in the control group (P = 0.29). Mi ssense mutations were found in 9 of 9 EOM tumors showing strong p53 nu clear immunostaining. No significant difference in the incidence of an euploidy was observed when EOM cases were compared with POC controls ( 65% vs. 63%). High tumor grade was strongly associated with HER-2/neu overexpression in the EOM group (P = 0.002). None of the parameters st udied were predictive of prognosis within the EOM and POC groups. CONC LUSIONS. Although overexpression of p53 protein, p53 gene mutations, a nd abnormal DNA content were similar between EOMs and POCs, EOMs demon strated almost twice the rate of HER-2/neu overexpression. This result suggests that distinct genetic events may be responsible for malignan t transformation in EOMs versus POCs. (C) 1997 American Cancer Society .