IDENTIFICATION OF HER-2 NEU ONCOGENE AMPLIFICATION BY FLUORESCENCE IN-SITU HYBRIDIZATION IN STAGE-I ENDOMETRIAL CARCINOMA/

Prognostic factors capable of detecting potential for aggressive disea se in early stage endometrial cancer might be useful in selecting pati ents for early adjuvant therapy. Sixty-three patients with surgical St age I endometrial carcinoma treated by hysterectomy with a mean follow -up of 55 months were evaluated for tumor type, grade, depth of myomet rial invasion, presence of vascular invasion, DNA ploidy, and HER-2/ne u overexpression by immunohistochemical techniques. These results were compared with HER-2/neu gene amplifications evaluated by fluorescence in situ hybridization (FISH) and their ability to predict disease sur vival. For FISH, sections 5 mu m thick of formalin-fixed, paraffin-emb edded tissues were processed using the Oncor Chromosome In Situ Hybrid ization System. Automated hybridization using the Ventana Gen was perf ormed with the Oncor unique sequence digoxigenin-labeled HER-2/neu DNA probe. Gene copy numbers were evaluated using the Zeiss Axioskop50 fl uorescence microscope. HER-2/neu amplification was noted in 24 (38%) o f 63 cases. By multivariate analysis, only aneuploidy (P = .04) and HE R-2/neu amplification by FISH (P = .04) independently correlated with survival. Although we saw a relationship between HER-2/neu protein exp ression and gene amplification, this trend did not achieve statistical significance, HER-2/neu oncogene amplification can be assessed using automated FISH on formalin-fixed, paraffin-embedded tissue. HER-2/neu amplification predicts poor outcome in Stage I endometrial cancer. HER -2/neu amplification status has potential use in the identification of patients with high risk of disease recurrence who might benefit from intensified therapy.