Clinico-pathologic comparison of type II endometrial cancers based on tamoxifen exposure

ObjectiveTo compare clinico-pathologic variables and protein expression of potential regulatory components in patients who develop type II endometrial cancer with and without antecedent tamoxifen.MethodsClinico-pathologic variables were compared for all surgically staged patients (2000–2008) with grade 3 endometrioid, papillary serous, clear cell, and carcinosarcoma of the uterus based on tamoxifen exposure [Tam (+) vs. Tam (−)]. Overall survival was analyzed using a multivariable Cox regression model and Kaplan–Meier estimates. Protein expression of ERα, PR, mTOR, p-mTOR, IGF-1R, EGFR, VEGF and HER-2/neu was compared by immunohistochemistry using a semiquantitative scoring system.ResultsOf 115 patients with high grade endometrial cancers, 15 received tamoxifen. These patients were older at diagnosis than Tam (−) patients. A higher percentage of Tam (+) patients had carcinosarcoma compared to Tam (−) patients (60% vs. 30%, P = 0.038). Overall survival for Tam (+) patients was shorter than Tam (−) patients (16.6 vs. 32.2 months, P = 0.004). The hazard ratio for death for Tam (+) patients was 2.53 (P = 0.014), controlling for age and stage. Intensity and extent of staining were similar for ERα, PR, VEGF, EGFR, p-mTOR and HER-2/neu. The average expression score for IGF-1R and mTOR in the Tam (+) group was significantly higher than the Tam (−) group: 10.3 vs 7.0, P = 0.001 and 6.0 vs 3.1, P = 0.029, respectively.ConclusionThere are differences in the biology of type II endometrial cancers that develop in women with prior tamoxifen exposure. Tamoxifen associated cancers show higher expression of IGF-1R and mTOR, which should be further investigated.

► Antecedent tamoxifen exposure was associated with shorter overall survival in patients who developed type II endometrial cancer.
► Expression of IGF-1R and mTOR is higher in type II endometrial cancers associated with tamoxifen use.