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

• Published in: Gynecologic oncology 2012-11, Vol.127 (2), p.316-320
• Main Authors: Tergas, Ana I, Buell-Gutbrod, Rebecca, Gwin, Katja, Kocherginsky, Masha, Temkin, Sarah M, Fefferman, Ann, Lengyel, Ernst, Yamada, S. Diane
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Clear Cell - chemically induced; Adenocarcinoma, Clear Cell - metabolism; Adenocarcinoma, Clear Cell - mortality; Adenocarcinoma, Clear Cell - pathology; Aged; Antineoplastic Agents, Hormonal - adverse effects; Biomarkers, Tumor - metabolism; Carcinoma, Endometrioid - chemically induced; Carcinoma, Endometrioid - metabolism; Carcinoma, Endometrioid - mortality; Carcinoma, Endometrioid - pathology; Carcinosarcoma - chemically induced; Carcinosarcoma - metabolism; Carcinosarcoma - mortality; Carcinosarcoma - pathology; Endometrial Neoplasms - chemically induced; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - mortality; Endometrial Neoplasms - pathology; Female; Follow-Up Studies; Hematology, Oncology and Palliative Medicine; Humans; IGF-1R; Immunohistochemistry; mTOR; Neoplasm Grading; Neoplasms, Glandular and Epithelial - chemically induced; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - mortality; Neoplasms, Glandular and Epithelial - pathology; Obstetrics and Gynecology; Prognosis; Receptor, IGF Type 1 - metabolism; Survival Analysis; Tamoxifen; Tamoxifen - adverse effects; Tissue Array Analysis; TOR Serine-Threonine Kinases - metabolism; Type II endometrial cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2012.07.105

Abstract Objective To compare clinico-pathologic variables and protein expression of potential regulatory components in patients who develop type II endometrial cancer with and without antecedent tamoxifen. Methods Clinico-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. Results Of 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. Conclusion There 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.