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Mechanisms of oncogenesis in colon versus rectal cancer
Author(s) -
Kapiteijn E.,
Liefers G. J.,
Los L. C.,
Klein Kranenbarg E.,
Hermans J.,
Tollenaar R. A. E. M.,
Moriya Y.,
van de Velde C. J. H.,
van Krieken J. H. J. M.
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.918
Subject(s) - colorectal cancer , medicine , immunohistochemistry , mlh1 , carcinogenesis , rectum , cancer , oncology , gastroenterology , pathology , dna mismatch repair
Observations support the theory that development of left‐ and right‐sided colorectal cancers may involve different mechanisms. This study investigated different genes involved in oncogenesis of colon and rectal cancers and analysed their prognostic value. The study group comprised 35 colon and 42 rectal cancers. Rectal cancer patients had been treated with standardized surgery performed by an experienced rectal cancer surgeon. Mutation analysis was performed for p53 in eight colon cancers and for APC and p53 in 22 rectal cancers. MLH1, MSH2, Bcl‐2, p53, E‐cadherin and β‐catenin were investigated by immunohistochemistry in all colorectal tumours. APC mutation analysis of the MCR showed truncating mutations in 18 of 22 rectal tumours (82%), but the presence of an APC mutation was not related to nuclear β‐catenin expression ( p =0.75). Rectal cancers showed significantly more nuclear β‐catenin than colon cancers (65% versus 40%, p =0.04). p53 mutation analysis corresponded well with p53 immunohistochemistry ( p <0.001). Rectal cancers showed significantly more immunohistochemical expression of p53 than colon cancers (64% versus 29%, p =0.003). In rectal cancers, a significant correlation was found between positive p53 expression and worse disease‐free survival ( p =0.008), but not in colon cancers. Cox regression showed that p53‐expression ( p =0.03) was an independent predictor for disease‐free survival in rectal cancers. This study concluded that rectal cancer may involve more nuclear β‐catenin in the APC/β‐catenin pathway than colon cancer and/or nuclear β‐catenin may have another role in rectal cancer independently of APC. The p53‐pathway seems to be more important in rectal cancer, in which it also has independent prognostic value. When prognostic markers are investigated in larger series, differences in biological behaviour between colon and rectal cancer should be considered. Copyright © 2001 John Wiley & Sons, Ltd.