Antibody-based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing

Cancer. 2002 Dec 1;95(11):2422-30. doi: 10.1002/cncr.10979.


Background: Germline mutations in the DNA mismatch repair genes, MSH2, MLH1, and others are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Due to the high costs of sequencing, cheaper screening methods are needed to identify HNPCC cases. Ideally, these methods should have a high sensitivity and identify all mutated cases without too many false-positive cases.

Methods: Sequencing was compared with microsatellite analysis and immunohistochemistry to detect the presence or absence of the mismatch repair proteins. In the current study, the authors examined 42 patients with colorectal carcinoma of whom 11 met the Amsterdam criteria and 31 were suspected to belong to HNPCC families. Thirty-five patients were examined by microsatellite analysis, 40 by immunohistochemical staining, and in 31 patients both the MLH1 and MSH2 genes were sequenced.

Results: Ninety-two percent of patients with germ line mutations were detected by either immunohistochemistry or microsatellite instability, indicating that a combination of these methods may be suitable for HNPCC screening. Microsatellite instability and abnormal immunohistochemical staining were found in 73% of the tumors. Concordance among the three methods was found in 74 % of the tumors.

Conclusions: The authors suggest that immunohistochemistry should be used in combination with microsatellite analysis to prescreen suspected HNPCC patients for the selection of cases where sequencing of the MLH1 and MSH2 mismatch repair genes is indicated.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Age Factors
  • Aged
  • Base Pair Mismatch
  • Carrier Proteins
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / immunology
  • Cost-Benefit Analysis
  • DNA Primers
  • DNA Repair
  • DNA-Binding Proteins*
  • False Positive Reactions
  • Germ-Line Mutation*
  • Humans
  • Immunohistochemistry
  • Mass Screening* / economics
  • Mass Screening* / methods
  • Microsatellite Repeats*
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / analysis
  • Nuclear Proteins
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / analysis
  • Sensitivity and Specificity


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