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Gut. 2002 Jul;51(1):56-9.

Frequent loss of SMAD4/DPC4 protein in colorectal cancers.

Author information

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

Abstract

BACKGROUND AND AIMS:

Loss of DNA sequences from chromosome 18q21 is a major genetic change in colorectal tumorigenesis. Multiple genes have been identified in this area. One of these, DPC4 (deleted in pancreatic cancer 4, also known as SMAD4), is mutated in a minor subset of colorectal carcinomas as well as in germlines of humans predisposed to colon tumours.

PATIENTS AND METHODS:

The involvement of SMAD4 in sporadic colorectal neoplasia was evaluated by immunohistochemistry in 53 unselected cases and 27 cases displaying microsatellite instability.

RESULTS:

SMAD4 expression was absent in 20 of 53 (38%) unselected colorectal carcinomas, and reduced in another 15 (28%) cases. However, 26 of 27 cancers displaying microsatellite instability and TGF-betaIIR mutations were positive for SMAD4 immunostaining.

CONCLUSIONS:

Loss of SMAD4 expression may play a more prominent role in colon cancer than anticipated based on genetic evidence, but not in mutator phenotype tumours.

PMID:
12077092
PMCID:
PMC1773263
DOI:
10.1136/gut.51.1.56
[Indexed for MEDLINE]
Free PMC Article

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