Synchronous endometrial and ovarian carcinomas: predictors of risk and associations with survival and tumor expression profiles

Cancer Causes Control. 2017 May;28(5):447-457. doi: 10.1007/s10552-017-0855-5. Epub 2017 Feb 13.

Abstract

Purpose: 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.

Keywords: Endometrial carcinoma; Endometrioid ovarian carcinoma; Endometriosis; Immunohistochemistry; MSH1; PMS2; PTEN; Prognosis.

MeSH terms

  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / mortality
  • Adenocarcinoma, Clear Cell / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Alberta
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Endometrioid / metabolism
  • Carcinoma, Endometrioid / mortality
  • Carcinoma, Endometrioid / pathology*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology*
  • Female
  • Humans
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2 / metabolism
  • MutL Protein Homolog 1 / metabolism
  • Neoplasms, Multiple Primary / metabolism
  • Neoplasms, Multiple Primary / mortality
  • Neoplasms, Multiple Primary / pathology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • PTEN Phosphohydrolase / metabolism
  • Prognosis
  • Registries
  • Risk

Substances

  • Biomarkers, Tumor
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • PMS2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1