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Mismatch repair deficiency and prognostic significance in patients with low-risk endometrioid endometrial cancers
  1. Soyoun Rachel Kim1,
  2. Annick Pina2,
  3. Arianne Albert3,
  4. Jessica N McAlpine4,
  5. Robert Wolber5,
  6. Blake Gilks5,
  7. Mark S Carey4 and
  8. Janice S Kwon4
  1. 1Gynecologic Oncology, University of Toronto, Toronto, Ontario, Canada
  2. 2Obstetrics and Gynaecology, Universite de Montreal, Montreal, Quebec, Canada
  3. 3Women’s Health Research Institute, Vancouver, British Columbia, Canada
  4. 4Division Gynecology Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada
  5. 5Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  1. Correspondence to Dr Janice S Kwon, Obstetrics and Gynecology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada; janice.kwon{at}vch.ca

Abstract

Objectives Mismatch repair deficiency is observed in 25%–30% of all endometrial cancers. This can be detected by the absence of mismatch repair protein staining on immunohistochemistry, and is used as a screen for Lynch syndrome. Only 10% of women with mismatch repair deficiency have Lynch syndrome, but mismatch repair deficiency may still have prognostic significance. The objective of this study was to compare clinical outcomes between mismatch repair-deficient and mismatch repair-proficient low-risk endometrioid endometrial cancers (stage IA, grade 1 or 2).

Methods This was a retrospective population-based cohort study of all low-risk endometrioid endometrial cancers (stage IA, grade 1 or 2) from the Vancouver Coastal Health Authority region from February 2011 to January 2016 that were assessed for mismatch repair deficiency. Any other histology, stage, or grade was excluded from the study. Primary outcome measures were progression-free survival and overall survival calculated using Kaplan–Meier method and log-rank tests. Cox proportional hazards model estimated the association between mismatch repair deficiency and recurrence and death after adjustment for covariates, expressed as hazard ratios (HRs). Secondary outcome measures were recurrence rates expressed per 100 person-years (p100py).

Results There were 475 patients diagnosed with low-risk endometrioid endometrial cancer, including 131 with mismatch repair-deficient (27.6%) and 344 with mismatch repair-proficient (72.4%) tumors. Women with mismatch repair-deficient tumors had worse progression-free survival (24 months; p=0.0082) and higher recurrence rates (3.56 p100py) compared with those with mismatch repair-proficient tumors (27 months; 1.21 p100py, p=0.04). The absolute number of recurrences was overall low. There were 11 recurrences out of 131 mismatch repair-deficient cases (8.4%) and 14 out of 344 mismatch repair proficient cases (4.1%). After adjustment for age, lymphovascular space invasion status, adjuvant therapy, and post-operative grade, mismatch repair-deficient status remained associated with a higher risk of recurrence (HR 3.56, 95% CI 2.01 to 5.95). There was no significant difference in overall survival between mismatch repair groups (mismatch repair-proficient group 27.5 months vs 25.0 months in the deficient group) (HR 1.23, 95% CI 0.49 to 3.10).

Conclusion In low-risk stage IA grade 1 or 2 endometrioid endometrial cancers, mismatch repair deficiency is associated with a higher recurrence rate than mismatch repair proficiency after adjustment for covariates, implying that mismatch repair deficiency reflects a different biology in endometrial cancer.

  • uterine cancer
  • endometrium
  • lynch syndrome II
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Footnotes

  • Contributors SRK was the primary and corresponding author, responsible for data collection, analysis and write-up, with close supervision from senior principal investigator, JK. AP helped build the database. AA was the statistician involved in data analysis. JMcA, RW, MC, and BG all contributed data and scientific expertise to the project.

  • Funding The authors declared funding from the University of British Columbia/Vancouver General Hospital/Carreressi Foundation

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article.

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