AMPLIFICATION AND OVEREXPRESSION OF HER-2 NEU (C-ERBB2) IN ENDOMETRIAL CANCERS - CORRELATION WITH OVERALL SURVIVAL/

Few molecular genetic alterations have been identified in endometrial cancers that are associated with poor clinical outcome, Overexpression of HER-2/neu, transforming growth factor alpha, and p53 proteins have all been associated with poor prognosis in women with endometrial can cer. In this study, the level of HER-2/neu gene amplification and expr ession was characterized in 92 endometrial cancers. Fluorescence in si tu hybridization (FISH) was used to characterize HER-2/neu gene copy n umber, and immunohistochemistry was used to characterize expression. F orty-seven of the 90 (52%) endometrial cancers were characterized as s howing moderate or high immunostaining. HER-2/neu gene amplification w as detected in 17 of 81 (21%) cases. Immunohistochemical staining and FISH results were both available for 80 cases, Fourteen of these cases showed both moderate or high immunostaining and gene amplification. C linical follow-up information was available for 76 women in this study , Women whose endometrial cancer exhibited HER-2/neu gene amplificatio n by FISH had a shorter overall survival than women whose endometrial cancer lacked amplification (P = 0.018), Likewise, tumors with moderat e or high HER-2/neu immunostaining were associated with a lower cumula tive overall survival than tumors with low immunostaining by log rank analysis (P < 0.0001), Multivariate analysis of survival rates reveale d HER-2/neu overexpression to be an independent predictor of overall s urvival (P = 0.0163), Among those patients with HER-2/neu overexpressi on, adjuvant chemotherapy or radiation therapy was associated with an improved overall survival (P = 0.039), However, among those women whos e tumor lacked overexpression, overall survival was not improved by ad juvant treatment.