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

Ana I. Tergas, Rebecca Buell-Gutbrod, Katja Gwin, Masha Kocherginsky, Sarah M. Temkin, Ann Fefferman, Ernst Lengyel, S. Diane Yamada

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)316-320
Number of pages5
JournalGynecologic oncology
Volume127
Issue number2
DOIs
StatePublished - Nov 1 2012

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Keywords

  • IGF-1R
  • Tamoxifen
  • Type II endometrial cancer
  • mTOR

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Tergas, A. I., Buell-Gutbrod, R., Gwin, K., Kocherginsky, M., Temkin, S. M., Fefferman, A., Lengyel, E., & Yamada, S. D. (2012). Clinico-pathologic comparison of type II endometrial cancers based on tamoxifen exposure. Gynecologic oncology, 127(2), 316-320. https://doi.org/10.1016/j.ygyno.2012.07.105