BMC Cancer 2002, 2 http://www.biomedcentral.com/1471-2407/2/25 alanine change. A lower frequency of KRAS mutations coordinated the results. Authors 1 and 4 both contributed has been found in distal tumors and an inverse relation- ship between MSI and alterations of KRAS and TP53 mu- tations has been described [22], a finding that is supported by our data with KRAS mutations in 6/30 tu- mors and nuclear expression of p53 in 18/30 rectal can- cers. -catenin is involved in cell-cell adhesion as well as in sig- nal transduction. Free -catenin is bound to the adenom- atosis polyposis coli (APC) protein and to glycogen synthase kinase 3B (GSK-3B), which phosphorylate ser- ine/threonine residues in -catenin and thereby destabi- lizes the protein, which is degraded by the ubiquitin- proteasome pathway. Mutations of APC or of the regula- tory domain of CTNNB1 has been demonstrated in color- ectal cancer and lead to stabilization and cytoplasmic accumulation of free -catenin [25,26]. Increased cyto- plasmic levels of -catenin allows the protein to enter the nucleus where it promotes transcriptional activation through the TCF/LEF transcription factors. We found no mutations in the regulatory domain (exon 3) of the CTNNB1 gene, but immunohistochemitry for -catenin revealed an increased cytoplasmic expression or a nuclear accumulation in 25/30 tumors. Nuclear accumulation of -catenin has been reported to occur at a higher frequency in rectal cancer than in colon cancer, whereas mutations affecting the CTNNB1 gene, have been reported to occur at a higher frequency in MMR-deficient tumors [26,27]. Conclusions We conclude that rectal cancer, also when developing in young patients, is frequently associated with DNA-aneu- ploidy, increased expression of p53 and -catenin, where- as MSI and mutations in KRAS occur at a low frequency. In this study only 10% of the rectal cancers from young patients were MSI-high, but all of these tumors showed loss of expression for MSH2, which suggests an underly- ing HNPCC-causing mutation. Thus, other mechanisms than defective MMR and HNPCC probably cause rectal cancer development in the majority of young patients. Competing interests None declared. Authors' contributions Author 1 was responsible for the design of the study, ob- tained tumor material, evaluated the immunohistochem- istry, performed clinical correlations and summarized the results. Author 2 reviewed the histopathological material. Author 3 performed the flow cytometric DNA analyses. Author 4 conceived of the study, evaluated the immuno- histochemistry, the MSI and the mutation analyses, and to the writing of the paper. Acknowledgments We would like to acknowledge Eva Rambech and Annette Persson for tech- nical assistance performing the immunohistochemistry. 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