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Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes
  1. Giorgio Bogani1,
  2. Maria Grazia Tibiletti2,
  3. Maria Teresa Ricci3,
  4. Ileana Carnevali2,
  5. Viola Liberale4,
  6. Biagio Paolini5,
  7. Massimo Milione4,
  8. Marco Vitellaro1,
  9. Ferdinando Murgia5,
  10. Valentina Chiappa1,
  11. Antonino Ditto4,
  12. Fabio Ghezzi6 and
  13. Francesco Raspagliesi4
  1. 1 Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy, Milano, Lombardia, Italy
  2. 2 Ospedale di Circolo Fondazione Macchi, University of Insubria, Varese, Lombardia, Italy
  3. 3 Unit of Hereditary Digestive Tract Tumors, Department of Surgery, Isituto Tumori Milano, Milan, Italy
  4. 4 Gynecologic Oncology, Isituto Tumori Milano, Milan, Italy
  5. 5 Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy
  6. 6 Obstetrics and Gynecology, University of Insubria, Varese, Italy
  1. Correspondence to Dr Giorgio Bogani, Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano 20133, Italy; giorgio.bogani{at}istitutotumori.mi.it

Abstract

Objective Women with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.

Methods Data from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.

Results Overall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.

Conclusions Non-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

  • endometrial neoplasms
  • Lynch syndrome II
  • uterine neoplasms
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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • 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.

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