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Endometrial Cancer Characteristics and Risk of Recurrence.

Lindsay E Borden1, Tonja M Locklear2, Douglas J Grider3

  • 1Department of Obstetrics and Gynecology, Roanoke, VA,USA.

American Journal of Clinical Pathology
|August 31, 2021
PubMed
Summary

Endometrial cancer with MLH1 hypermethylation (hMLH1+) shows worse prognosis and higher recurrence rates, even in early stages. This highlights the importance of MMR status in predicting outcomes for these tumors.

Keywords:
DNA mismatch repairEndometrial neoplasmsEpigenomicsLynch syndromeMicrosatellite repeats

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Area of Science:

  • Gynecologic Oncology
  • Molecular Pathology
  • Cancer Genomics

Background:

  • Mismatch repair (MMR) deficiency is a key factor in endometrial cancer development.
  • Stratifying endometrial adenocarcinomas by MMR status is crucial for understanding prognosis.
  • MLH1 hypermethylation (hMLH1+) represents a distinct molecular subtype with potential implications for treatment and outcomes.

Purpose of the Study:

  • To delineate clinicopathologic features of endometrial adenocarcinomas.
  • To evaluate survival outcomes based on MMR status.
  • To identify prognostic significance of MLH1 hypermethylation in endometrial cancer.

Main Methods:

  • Retrospective analysis of 316 women with endometrioid adenocarcinomas (2012-2017).
  • Classification into intact MMR (MMR+), probable MMR mutation (MMR-), and MLH1 hypermethylation (hMLH1+) groups.
  • Analysis of demographics, histology, invasion, recurrence, and survival.

Main Results:

  • hMLH1+ patients were older, had higher-grade tumors, and more lymphovascular invasion.
  • Early-stage hMLH1+ patients showed significantly higher recurrence rates (15.3% vs 2.3% MMR+).
  • MLH1 hypermethylation was an independent predictor of recurrence (OR, 5.09) and reduced recurrence-free survival (HR, 7.40).

Conclusions:

  • Endometrial cancers with MLH1 hypermethylation exhibit poorer prognostic features.
  • hMLH1+ tumors recur more frequently, challenging traditional risk stratification.
  • MMR status, particularly hMLH1+, is a critical determinant of outcomes in endometrial adenocarcinoma.