Evaluation of microsatellite instability and immunohistochemistry for the prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon cancer families Academic Article uri icon

Overview

MeSH Major

  • Colorectal Neoplasms, Hereditary Nonpolyposis
  • DNA-Binding Proteins
  • Germ-Line Mutation
  • Neoplasm Proteins
  • Proto-Oncogene Proteins

abstract

  • Forty-eight hereditary nonpolyposis colorectal carcinoma (HNPCC) families for which a tumor sample was available were evaluated for the presence of germ-line mutations in MSH2 and MLH1, tumor microsatellite instability (MSI), and where possible, expression of MSH2 and MLH1 in tumors by immunohistochemistry. Fourteen of 48 of the families had a germ-line mutation in either MSH2 or MLH1 that could be detected by genomic DNA sequencing, and 28 of 48 of the families had MSI-H tumors. Four additional families showed loss of expression of MSH2, and one additional family showed loss of expression of MLH1 but did not have germ-line mutations in MSH2 or MLH1 that could be detected by DNA sequencing. MSI-H, as defined using the National Cancer Institute recommended five-microsatellite panel, had a 100% sensitivity for identifying samples having MSH2 or MLH1 mutations or loss of expression. In contrast, loss of MSH2 and MLH1 expression did not identify all samples having germ-line mutations in MSH2 or MLH1, because in five cases, a mutant protein product was expressed that could be detected by IHC. A combination of the Bethesda criteria for HNPCC and an MSI-H phenotype defined the smallest number of cases having all of the germ-line MSH2 and MLH1 mutations that could be detected by DNA sequencing.

publication date

  • June 15, 2002

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 12067992

Additional Document Info

start page

  • 3485

end page

  • 92

volume

  • 62

number

  • 12