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Endometrial cancer risk and survival by tumor MMR status

Christina M Nagle1,2, Tracy A O'Mara3, Yen Tan3

  • 1Population Health Department, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia.

Journal of Gynecologic Oncology
|March 14, 2018
PubMed
Abstract

Insights

Endometrial cancer (EC) risk is not linked to DNA mismatch repair (MMR) status. However, somatic MMR-deficient endometrioid subtype tumors are associated with worse EC-specific survival compared to MMR-proficient tumors.

Area of Science:

  • Gynecologic Oncology
  • Cancer Genomics
  • Molecular Pathology

Background:

  • Tumor DNA mismatch repair (MMR) status may influence endometrial cancer (EC) risk and patient outcomes.
  • Understanding the distinct roles of germline and somatic MMR deficiency is crucial for accurate prognostication.

Purpose of the Study:

  • To assess the association between tumor MMR status (MMR-proficient, somatic MMR-deficient, germline MMR-deficient) and EC risk.
  • To evaluate the impact of tumor MMR status on survival following an EC diagnosis.

Main Methods:

  • Analysis of data from the Australian National Endometrial Cancer Study (ANECS) (2005-2007).
  • Logistic regression for EC risk analysis (698 cases/691 controls).
  • Proportional hazards models for survival analysis (728 cases), linked with the Australian National Death Index.

Main Results:

  • No significant differences in established EC risk factors by tumor MMR status.
  • Overall and EC-specific survival did not differ across MMR status groups for all EC subtypes.
  • Among endometrioid subtype EC, somatic MMR-deficient tumors showed significantly worse EC-specific survival (HR=2.18; 95% CI=1.19-4.01) compared to MMR-proficient tumors.

Conclusions:

  • Endometrial cancer risk is not associated with MMR status.
  • Distinguishing germline from somatic MMR deficiency is important.
  • Patients with somatic MMR-deficient endometrioid EC have poorer survival outcomes than those with MMR-proficient tumors.
Keywords:
DNA Mismatch RepairEndometrial NeoplasmsRiskSurvival

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