Mismatch repair deficiency screening via immunohistochemical staining in young Asians with colorectal cancers

World J Surg. 2013 Oct;37(10):2468-75. doi: 10.1007/s00268-013-2134-2.

Abstract

Background: The incidence of mismatch repair deficiency in colorectal cancer (CRC) in young people remains unknown in Asians. The present study assessed the clinicopathological features and efficacy of immunohistochemistry screening for Lynch syndrome in young Asian CRC patients.

Material and methods: This was a retrospective review conducted in Singapore General Hospital between January 2006 and December 2010 of 240 unrelated patients under the age of 50. All patients had immunohistochemical (IHC) staining for mismatch repair proteins in resected CRC specimen data retrieved from a prospective computerized database.

Results: A total of 21 % (n = 51) of the patients had abnormal IHC staining. Loss of staining for MLH1, MSH2, MSH6, and PMS2 proteins was observed in 10, 4, 6, and 13 % of tumors, respectively. Of the 22 patients who had abnormal staining of MLH1, 13 had concomitant abnormal staining for PMS2. One tumor specimen had abnormal staining in all four proteins. If the Amsterdam criteria alone were to be used, 86 % (n = 44) of the cohort would have not been detected for mismatch repair gene defects.

Conclusions: The overall burden of germline mismatch repair deficiency in the Singapore population may be as high as 21 %. The Amsterdam criteria alone are inadequate to detect Lynch syndrome patients. The use of IHC staining of at least four mismatch repair proteins is a useful screening strategy for Lynch syndrome diagnosis. Routine screening of mismatch repair deficiency may be recommended for all young Asian CRC patients.

Publication types

  • Evaluation Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adenosine Triphosphatases / deficiency
  • Adult
  • Age Factors
  • Asian People
  • Biomarkers, Tumor / deficiency*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / enzymology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / ethnology
  • DNA Repair Enzymes / deficiency*
  • DNA-Binding Proteins / deficiency
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Immunohistochemistry
  • Logistic Models
  • Male
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / deficiency
  • Nuclear Proteins / deficiency
  • Retrospective Studies
  • Singapore

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • Nuclear Proteins
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes