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Colorectal cancer
Frequent loss of SMAD4/DPC4 protein in colorectal cancers
  1. R Salovaara1,
  2. S Roth2,
  3. A Loukola2,
  4. V Launonen2,
  5. P Sistonen3,
  6. E Avizienyte2,
  7. P Kristo2,
  8. H Järvinen4,
  9. S Souchelnytskyi5,
  10. M Sarlomo-Rikala6,
  11. L A Aaltonen7
  1. 1Department of Medical Genetics and Department of Pathology, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland
  2. 2Department of Medical Genetics, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland
  3. 3Finnish Red Cross Blood Transfusion Service, Kivihaantie 7, FIN-00310 Helsinki, Finland
  4. 4Second Department of Surgery, Helsinki University Central Hospital, PO Box 340, FIN-00029 Helsinki, Finland
  5. 5Ludwig Institute for Cancer Research, PO Box 595, S-751 24 Uppsala, Sweden
  6. 6Department of Pathology, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland
  7. 7Department of Medical Genetics, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland, and Department of Oncology, Helsinki University Central Hospital, PO Box 180, FIN-00029 Helsinki, Finland
  1. Correspondence to:
    Dr L A Aaltonen, Department of Medical Genetics, Haartman Institute, PO Box 63, FIN-00014 University of Helsinki, Finland;
    lauri.aaltonen{at}helsinki.fi.

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-βIIR 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.

  • SMAD4
  • DPC4
  • colorectal carcinoma
  • immunohistochemistry
  • MSI, microsatellite instability
  • LOH, loss of heterozygosity
  • RT-PCR, reverse transcription-polymerase chain reaction
  • TGF-βIIR, transforming growth factor β type II receptor

https://doi.org/10.1136/gut.51.1.56

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