Clinical factors as prognostic variables among molecular subgroups of endometrial cancer

Anne Kolehmainen; Annukka Pasanen; Taru Tuomi; Riitta Koivisto-Korander; Ralf Bützow; Mikko Loukovaara

doi:10.1371/journal.pone.0242733

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.

Authors

Anne Kolehmainen¹, Annukka Pasanen², Taru Tuomi¹, Riitta Koivisto-Korander¹, Ralf Bützow^{1

2}, Mikko Loukovaara¹

Affiliations

¹ Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
² Department of Pathology, Helsinki University Hospital and Research Program in Applied Tumor Genomics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

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

Grants and funding

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.