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Impact of gene-specific germline pathogenic variants on presentation of endometrial cancer in Lynch syndrome
  1. Giorgio Bogani1,
  2. Maria Teresa Ricci2,
  3. Marco Vitellaro2,
  4. Antonino Ditto1,
  5. Valentina Chiappa1 and
  6. Francesco Raspagliesi1
  1. 1 Department of Gynecologic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy
  2. 2 Unit of Hereditary Digestive Tract Tumors, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Milano, Italy
  1. Correspondence to Dr Giorgio Bogani, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano 20100, Italy; giorgiobogani{at}yahoo.it

Abstract

Objective Lynch syndrome is a risk factor for developing endometrial carcinoma. Our aim was to evaluate the impact of gene-specific germline pathogenic variants on clinical features of patients affected by endometrial cancer.

Methods Patients with a diagnosis of endometrial cancer and with a germline pathogenic variant in mismatch repair genes were reviewed. Patients were classified on the basis of classes of risk according to the ESGO-ESGO-ESTRO (European Society of Medical Oncology/European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology) guidelines. One-way analysis of variance (ANOVA) and Kruskal-Wallis test were performed to compare three groups of continuous parametric and non-parametric variables, respectively. χ2 test was used to analyze proportions.

Results Overall, 68 patients with endometrial cancer and Lynch syndrome were evaluated. Ten (14.7%) patients were excluded because of absence of information about the gene involved in Lynch syndrome, thus leaving 58 (85.3%) patients available for the final analysis. MLH1, MSH2, and MSH6 pathogenic variants were observed in 19 (32.7%), 33 (56.9%), and six (10.3%) patients, respectively. Mean±SD age at endometrial cancer diagnosis was 51±6.4, 43.5±7.4, and 60.3±8.8 years (p=0.0002). Prevalence of non-endometrioid endometrial cancer was 15.7%, 24.2%, and 0% in the MLH1, MSH2, and MSH6 groups, respectively (p=0.345). According to the ESMO-ESGO-ESTRO classification, low, intermediate, and high risk endometrial cancer accounted for 47.3%, 10.5%, and 42.1% of the MLH1 group, 57.6%, 3%, and 39.4% of the MSH2 group, and 50%, 50%m and 0% of the MSH6 group (p=0.009).

Conclusions Patients with MLH1 and MSH2 pathogenic variants are at a higher risk of early onset of endometrial cancer than patients with MSH6 pathogenic variants.

  • lynch syndrome
  • endometrial cancer
  • MLH1
  • MSH2
  • MSH6
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Footnotes

  • Contributors GB: manuscript preparation; data analysis; statistical analysis. MTR: data collection; data analysis; reviewing the manuscript. MV: data collection; data analysis; reviewing the manuscript. AD: data collection; data analysis; reviewing the manuscript. VC: data collection; data analysis; reviewing the manuscript. FR: data collection; data analysis; reviewing the manuscript.

  • 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 Obtained.

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

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