title: Synchronous endometrial and ovarian carcinomas: predictors of risk and associations with survival and tumor expression profiles.
abstract: OBJECTIVE
  Synchronous endometrial and ovarian tumors (SEOs) are diagnosed in 10% of ovarian cancer patients. We examined predictors of SEOs, evaluated associations of SEOs with survival and characterized ovarian tumor profiles using immunohistochemistry.
  
  
  METHODS
  We included patients with endometrioid (n = 180) and clear cell (n = 165) ovarian carcinoma identified from the Alberta Cancer Registry between 1979 and 2010 for whom we abstracted medical records and constructed tumor tissue microarrays (TMAs). A concurrent diagnosis of endometrial cancer was obtained from the medical chart. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs. Protein expression in ovarian tumors of patients with and without SEOs was evaluated using Fisher's exact test.
  
  
  RESULTS
  Comparing 52 patients with SEO tumors to 293 patients with endometrioid or clear cell ovarian carcinomas, endometriosis at the ovary (OR = 0.45, 95% CI = 0.23-0.87, p = 0.02) was the strongest predictor of decreased risk in multivariable models. Premenopausal status (OR = 2.17, 95% CI = 0.92-5.13, p = 0.08) and lower pre-treatment CA125 levels (OR = 0.17, 95% CI = 0.02-1.32, p = 0.09) showed weaker associations. There were no significant differences in survival between patients with or without SEO tumors. More patients with SEO tumors compared to endometrioid ovarian carcinoma were deficient in MLH1, PMS2 and PTEN (p ≤ 0.03).
  
  
  CONCLUSIONS
  Endometriosis may not be the mechanism by which SEO cancers arise. Altered tumor oncoprotein expression between women with and without SEOs indicates important biological differences although this did not translate into prognostic differences.
authors.affiliation: Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Bioengineering Building, MSC955, 68 President Street, Charleston, SC, 29425, USA. kelemen@musc.edu.|Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC, 29425, USA. kelemen@musc.edu.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.affiliation: Department of Pathology, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania.|Calgary Laboratory Services/Alberta Health Services, Department of Pathology and Laboratory Medicine, University of Calgary, 1403 29 Street NW, Calgary, AB, T2N 2T9, Canada.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Rambau
authors.affiliation: Alberta Health Services-Cancer Control Alberta, 2210 2nd Street SW, Calgary, AB, T2S 3C3, Canada.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Koziak
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, S5-131 Lois Hole Hospital, Royal Alexandra Hospital, 10240 Kingsway Ave, Edmonton, AB, T5H 3V9, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Steed
authors.affiliation: Calgary Laboratory Services/Alberta Health Services, Department of Pathology and Laboratory Medicine, University of Calgary, 1403 29 Street NW, Calgary, AB, T2N 2T9, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000416:Alberta; D014408:Biomarkers, Tumor / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2 / Q000378:metabolism; D000070957:MutL Protein Homolog 1 / Q000378:metabolism; D009378:Neoplasms, Multiple Primary / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011379:Prognosis; D012042:Registries; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1
keywords: Endometrial carcinoma; Endometrioid ovarian carcinoma; Endometriosis; Immunohistochemistry; MSH1; PMS2; PTEN; Prognosis