Frequent loss of SMAD4/DPC4 protein in colorectal cancers

Egle Mcdonald, R. Salovaara, S. Roth, A. Loukola, V. Launonen, P. Sistonen, E. Avizienyte, P. Kristo, H. Järvinen, S. Souchelnytskyi, M. Sarlomo-Rikala, Lauri A. Aaltonen

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)56-59
    Number of pages3
    JournalGut
    Volume51
    Issue number1
    DOIs
    Publication statusPublished - 2002

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