Clinical factors as prognostic variables among molecular subgroups of endometrial cancer

PLoS One. 2020 Nov 24;15(11):e0242733. doi: 10.1371/journal.pone.0242733. eCollection 2020.

Abstract

Background: Clinical factors may influence endometrial cancer survival outcomes. We examined the prognostic significance of age, body mass index (BMI), and type 2 diabetes among molecular subgroups of endometrial cancer.

Methods: This was a single institution retrospective study of patients who underwent surgery for endometrial carcinoma between January 2007 and December 2012. Tumors were classified into four molecular subgroups by immunohistochemistry of mismatch repair (MMR) proteins and p53, and sequencing of polymerase-ϵ (POLE). Overall, cancer-related, and non-cancer-related mortality were estimated using univariable and multivariable survival analyses.

Results: Age >65 years was associated with increased mortality rates in the whole cohort (n = 515) and in the "no specific molecular profile" (NSMP) (n = 218) and MMR deficient (MMR-D) (n = 191) subgroups during a median follow-up time of 81 months (range 1‒136). However, hazard ratios for cancer-related mortality were non-significant for NSMP and MMR-D. Diabetes was associated with increased overall and non-cancer-related mortality in the whole cohort and MMR-D subgroup. Overweight/obesity had no effect on outcomes in the whole cohort, but was associated with decreased overall and cancer-related mortality in the NSMP subgroup, and increased overall and non-cancer-related mortality in the MMR-D subgroup. Overweight/obesity effect on cancer-related mortality in the NSMP subgroup remained unchanged after controlling for confounders. High-risk uterine factors were more common, and estrogen and progesterone receptor expression less common in NSMP subtype cancers of normal-weight patients compared with overweight/obese patients. No clinical factors were associated with outcomes in p53 aberrant (n = 69) and POLE mutant (n = 37) subgroups. No cancer-related deaths occurred in the POLE mutant subgroup.

Conclusions: The prognostic effects of age, BMI, and type 2 diabetes do not appear to be uniform for the molecular subgroups of endometrial cancer. Our data support further evaluation of BMI combined with genomics-based risk-assessment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • DNA Mismatch Repair*
  • DNA Polymerase II* / genetics
  • DNA Polymerase II* / metabolism
  • Disease-Free Survival
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / mortality
  • Endometrial Neoplasms* / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Mutation*
  • Poly-ADP-Ribose Binding Proteins* / genetics
  • Poly-ADP-Ribose Binding Proteins* / metabolism
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Poly-ADP-Ribose Binding Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • DNA Polymerase II
  • POLE protein, human

Grant support

This study was supported by Helsinki University Hospital research funds. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.