title: Clinico-pathologic comparison of type II endometrial cancers based on tamoxifen exposure.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, University of Chicago, USA.
authors: Ana I
authors: AI
authors: Tergas
authors: Rebecca
authors: R
authors: Buell-Gutbrod
authors: Katja
authors: K
authors: Gwin
authors: Masha
authors: M
authors: Kocherginsky
authors: Sarah M
authors: SM
authors: Temkin
authors: Ann
authors: A
authors: Fefferman
authors: Ernst
authors: E
authors: Lengyel
authors: S Diane
authors: SD
authors: Yamada
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000139:chemically induced / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000139:chemically induced / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002296:Carcinosarcoma / Q000139:chemically induced* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D060787:Neoplasm Grading; D009375:Neoplasms, Glandular and Epithelial / Q000139:chemically induced* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013629:Tamoxifen / Q000009:adverse effects*; D046888:Tissue Array Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D013629:Tamoxifen; C546842:MTOR protein, human; D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases