BMC Cancer 2002, 2 http://www.biomedcentral.com/1471-2407/2/25 a c b d Figure 1 Immunohistochemical staining of tumor 10 a) normal nuclear staining for MLH1 in the tumor as well as in stromal tis- sue, b) loss of nuclear expression of MSH2 in tumor tissue but retained staining in stromal cells, c) nuclear staining for p53, and d) membraneous and intense cytoplasmic staining for -catenin. tions occurred in codon 12 and one in codon 13, whereas no mutation was detected in codon 61. All 6 tumors with KRAS mutations displayed immunohistochemical p53 protein expression. MSI was found in 3 tumors and the re- maining 27 tumors were MSS. All 30 tumors displayed normal expression of MLH1, whereas loss of expression for MSH2 was detected in 3 tumors. A family history of colorectal cancer (in 2 patients in combination with en- dometrial cancer) was reported in 8/28 evaluable patients, 2 of which also fulfilled the Amsterdam II criteria for the diagnosis of HNPCC. Discussion We characterized 30 rectal cancers from patients younger than 50 years at diagnosis with respect to tumor biologic phenomena associated with the MSI and the CIN path- ways for colorectal tumor development. Rectal cancer has been associated with a higher frequency of aneuploidy, MSS tumors, mutations in KRAS and TP53 and nuclear ac- cumulation of -catenin compared to colon cancer, which probably reflects different preferred pathways in the de- velopment of these tumor types [3,12,14–18]. Our find- ings of high frequencies of MSS (27/30) tumors, aneuploidy (21/30), immunohistochemical p53 expres- sion (18/30) and increased -catenin expression (25/30) (Table 3) is in line with previous reports of genetic altera- tions in rectal cancer, but support such a model for the de- velopment of rectal cancer also in the majority of young patients. Page 5 of 8 (page number not for citation purposes)