Endometrial cancer in Lynch syndrome

Int J Cancer. 2022 Jan 1;150(1):7-17. doi: 10.1002/ijc.33763. Epub 2021 Sep 9.


Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.

Keywords: Lynch syndrome; endometrial cancer; microsatellite instability; mismatch repair.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications*
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / etiology
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Female
  • Germ-Line Mutation*
  • Humans
  • Microsatellite Instability*


  • DNA Repair Enzymes