Expression und prognostische Bedeutung von DNA-Reparaturproteinen beim kolorektalen Karzinom – BRCA-1 und ATM als neue unabhängige Prognose-faktoren

Aims: Failure of DNA double strand break repair may result in chromosomal instability, a common phenomenon in colorectal cancer. The expression pattern of DNA double strand break repair proteins and their putative prognostic value have not been investigated in detail in colorectal cancer.

Methods: The expression of DNA DSB repair proteins ATM, BRCA1, BRCA2, Ku70 and Ku80 was investigated by immunohistochemistry in a series of 342 sporadic colorectal carcinomas and compared with clinicopathological data, patient survival, as well as expression of Ki67 and mismatch repair proteins MLH1 and MSH2.

Results: Expression of ATM, BRCA1 and BRCA2 was frequently reduced in colorectal cancer, whereas the expression of Ku70 and Ku80 was similar to that of normal colon mucosa. Low expression of ATM and BRCA1 was related to loss of MLH1 or MSH2 expression but not to Ki67 expression. Loss of ATM or BRCA1 expression was related to shorter patient survival and proved to be independent of established prognostic markers in multivariate analysis.

Conclusions: The expression of ATM and BRCA1 seems to play an important role in determining patient prognosis and response to adjuvant therapy in colorectal cancer. Thus, the results from our study may be useful in designing optimal therapeutic strategies for the treatment of colorectal cancer in the near future. Our study also suggests a possible link between expression of DNA mismatch repair and DNA double strand break repair proteins in colorectal cancer which warrants further investigation.