BACKGROUND AND PURPOSE:

• Lynch syndrome is inherited in an autosomal dominant pattern that predisposes to certain cancers (see ‘Related ObG Topics’ below)
• While most commonly known for its association with colon cancer, women often present with endometrial cancer
• Lynch syndrome screening includes
  • Tumor-based test: Immunohistochemistry (IHC) testing to identify mismatch repair (MMR) protein deficiency | Microsatellite instability (MSI) testing
  • If above positive: Germline testing to find a pathogenic variant in one of the MMR genes
• Experts have called for universal screening for Lynch syndrome in women with endometrial cancer
• Ryan et al. (Genetics in Medicine, 2019) investigated the outcomes of testing for Lynch syndrome in endometrial cancer patients
  • What proportion of endometrial cancer patients would likely need to receive definitive germline testing for variants following initial tests?
  • What proportion of these patients would be confirmed to have LS using next-generation sequencing (NGS)?

METHODS:

• Systematic review
• Inclusion criteria
  • Studies investigating Lynch syndrome in women with endometrial cancer
  • English language | females >18 years
  • Studies that used either direct germline analysis for pathogenic variants of MMR genes or other molecular diagnostic methods
• Data analysis
  • Proportions of test positivity were calculated by random and fixed-effects meta-analysis models

RESULTS:

• 53 studies included | 12,633 EC patients
• Overall proportion of endometrial tumors with
  • MSI: 0.27 (95% CI, 0.25–0.28)
  • MMR deficiency with IHC: 0.26 (95% CI, 0.25–0.27)
  • 0.29 of women with abnormal tumor testing had pathogenic variants on germline testing (95% CI, 0.25–0.33)
• Preselection (e.g., age or other clinical findings) did not significantly alter the results)

CONCLUSION:

• Approximately 3% of endometrial cancers are caused by Lynch syndrome
  • This prevalence is similar to that found in colorectal cancers
• The data from this study supports implementation of universal Lynch screening in women with endometrial cancer
• With knowledge of Lynch syndrome diagnosis
  • Women can be placed in to colorectal cancer surveillance programs
  • Cascade testing can be offered to family members

Learn More – Primary Sources:

The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis

Related ObG Topics: