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Frequent loss of SMAD4/DPC4 protein in colorectal cancers

R Salovaara1, S Roth, A Loukola

  • 1Department of Medical Genetics, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland.

Gut
|June 22, 2002
PubMed
Abstract

Insights

Loss of SMAD4 expression is frequent in sporadic colon cancer, suggesting a significant role in tumorigenesis. However, SMAD4 is typically retained in microsatellite instability-driven tumors.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Chromosome 18q21 deletions are key in colorectal cancer.
  • SMAD4 (DPC4) is a gene in this region, implicated in some colorectal carcinomas and hereditary colon cancer syndromes.

Purpose of the Study:

  • To investigate the role of SMAD4 in sporadic colorectal neoplasia.
  • To assess SMAD4 expression in colorectal tumors with and without microsatellite instability.

Main Methods:

  • Immunohistochemistry was used to evaluate SMAD4 expression.
  • The study included 53 unselected colorectal carcinomas and 27 cases with microsatellite instability.

Main Results:

  • SMAD4 expression was lost or reduced in 66% of unselected colorectal carcinomas (38% absent, 28% reduced).
  • In contrast, 96% of microsatellite instability-high tumors with TGF-betaIIR mutations retained SMAD4 expression.

Conclusions:

  • Loss of SMAD4 expression appears to be a significant event in a substantial proportion of sporadic colorectal cancers.
  • SMAD4 is generally preserved in colorectal cancers with a mutator phenotype, indicating distinct pathways.

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