[Mismatch pair defective phenotype in hereditary nonpolyposis colorectal cancer in the Chinese]

Zhonghua Zhong Liu Za Zhi. 2003 Sep;25(5):420-4.
[Article in Chinese]

Abstract

Objective: To study the protein expression pattern of DNA mismatch repair genes hMSH(2), hMLH(1) and the microsatellite instability (MSI) status in the tumor tissue from hereditary nonpolyposis colorectal cancer in the Chinese.

Methods: Fifty-eight families fulfilling different clinical criteria including Amsterdam Criteria (AC) (22/24 families, 38 tumors), Japanese Criteria (JC) (12/15 families, 16 tumors) and Bethesda Guidelines (BG) (12/19 patients, 13 tumors) were studied. Monoclonal antibodies against hMSH(2), hMLH(1) proteins and a panel of microsatellite markers (5 loci) including BAT26, BAT25, D2S123, D5S346 and D17S250 were used for study.

Results: MSI-H was identified in all 22 (100%) AC tumors, with 81.8% (18/22) showing altered hMSH(2) or hMLH(1) expression; in 14/15 (93.8%) JC cancer, 1/1 (100%) JC adenoma, with 45.5% (5/11) showing altered hMSH(2) or hMLH(1) expression; and in 7/13 (53.8%) BG tumors, with 4/7 showing loss of hMSH(2) or hMLH(1) gene expression.

Conclusion: The frequency of MSI-H and loss of mismatch repair protein are different in the families fulfilling different clinical criteria. Amsterdam Criteria and Japanese Criteria are the two most useful criterion systems for identifying mismatched repair defective tumors. However, Bethesda Guidelines should also be used for detecting more such tumors. The combination of immunohistochemical methods and microsatellite instability analysis is an effective strategy to detect the mismatch repair defective tumors. A close correlation does exist between hMSH(2), hMLH(1) protein expression pattern and MSI status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Base Pair Mismatch*
  • Carrier Proteins
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Repair*
  • DNA-Binding Proteins*
  • Humans
  • Immunohistochemistry
  • Microsatellite Repeats
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Proto-Oncogene Proteins / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein