Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome

Cancer. 2018 Aug 1;124(15):3145-3153. doi: 10.1002/cncr.31534. Epub 2018 May 11.

Abstract

Background: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Screening of all CRCs for LS is currently recommended, but screening of ECs is inconsistent. The objective of this study was to determine the added value of screening both CRC and EC tumors in the same population.

Methods: A prospective, immunohistochemistry (IHC)-based screening program for all patients with newly diagnosed CRCs and ECs was initiated in 2011 and 2013, respectively, at 2 centers (primary and tertiary). Genetic testing was recommended for those who had tumors with absent mutS homolog 2 (MSH2), MSH6, or postmeiotoic segregation increased 2 (PMS2) expression and for those who had tumors with absent mutL homolog 1 (MLH1) expression and no v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or MLH1 promoter methylation. Amsterdam II criteria, revised Bethesda criteria, and scores from prediction models for gene mutations (the PREMM1,2,6 and PREMM5 prediction models) were ascertained in patients with LS.

Results: In total, 1290 patients with CRC and 484 with EC were screened for LS, and genetic testing was recommended for 137 patients (10.6%) and 32 patients (6.6%), respectively (P = .01). LS was identified in 16 patients (1.2%) with CRC and in 8 patients (1.7%) with EC. Among patients for whom genetic testing was recommended, the LS diagnosis rate was higher among those with EC (25.0% vs 11.7%, P = .052). The Amsterdam II criteria, revised Bethesda criteria, and both PREMM calculators would have missed 62.5%, 50.0%, and 12.5% of the identified patients with LS, respectively.

Conclusions: Expanding a universal screening program for LS to include patients who had EC identified 50% more patients with LS, and many of these patients would have been missed by risk assessment tools (including PREMM5 ). Universal screening programs for LS should include both CRC and EC. Cancer 2018. © 2018 American Cancer Society.

Keywords: Lynch syndrome; colorectal cancer; endometrial cancer; hereditary cancer syndromes; universal screening.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Colonic Neoplasms* / diagnosis
  • Colonic Neoplasms* / epidemiology
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / epidemiology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / pathology
  • DNA-Binding Proteins / genetics
  • Early Detection of Cancer / methods
  • Endometrial Neoplasms* / diagnosis
  • Endometrial Neoplasms* / epidemiology
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Testing*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2 / genetics
  • MutL Protein Homolog 1 / genetics
  • MutS Homolog 2 Protein / genetics
  • Mutation

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • Mismatch Repair Endonuclease PMS2
  • MLH1 protein, human
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • PMS2 protein, human