HER-2/neu expression is associated with increased tumor cell proliferation, loss of hormone receptors and an aggressive phenotype in a population based setting of endometrial carcinomas

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 5040 OBJECTIVE: To investigate the distribution of HER-2/neu and EGFR expression in curettage material from a population based patient series with endometrial carcinoma in relation to clinico-pathologic characteristics, proliferative activity, receptor status in tumor and survival. STUDY DESIGN: Preoperative curettage material was collected from a population based series of 316 endometrial carcinomas from Norway with long and complete follow-up. Curettage specimens were studied immunohistochemically for HER-2/neu, EGFR and Ki-67 expression. RESULTS: Positive expression of HER-2/neu was seen in 23% and was significantly correlated to high FIGO stage (p=0.03), serous /clear cell histological subtype (p=0.0001), high histologic grade (p=0.007) and aneuploidy (p=0.02). Patients with positive expression of HER-2/neu had 79% 5-year survival compared to 72% for low HER-2/neu expression (p=0.18). Positive HER-2/neu expression in tumors was significantly correlated to loss of estrogen (p=0.04) and progesterone receptors (p=0.001) and to high tumor proliferation (p=0.01). Expression of EGFR was examined with three different antibodies, but none showed significant correlation to any clinico-pathologic variables, other tumor markers or survival. Proliferative activity in curettage material and the corresponding hysterectomy specimens were significantly correlated. High proliferation estimated in tumor from the hysterectomy specimens showed the strongest correlation with high FIGO stage (p=0.01), serous /clear cell histological subtype (p=0.01), high histologic grade (p=0.002), other prognostic markers and prognosis (p=0.03). CONCLUSION: Positive expression of HER-2/neu in curettage material is common in endometrial carcinomas and identifies tumors with aggressive phenotype, high proliferation and loss of hormonal receptors. These results motivate further clinical trials with trastuzumab based on molecular HER-2/neu status in tumors.