BMC Cancer 2002, 2 http://www.biomedcentral.com/1471-2407/2/25 Table 3: Summary of molecular genetic alterations Tumor no. MSI MSH2 MLH1 B-cat. TP53 KRAS mut. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 DI 2.1 1.1 1.4 4.5 2.0 1.4 1.7 1.0 1.5 1.0 1.0 1.0 1.6 1.0 1.0 1.0 1.0 1.1 1.1 1.3 1.8 1.3 1.2 1.7 1.0 2.0 1.2 1.6 1.2 1.1 - - - - - - - + - + - + - - - - - - - - - - - - - - - - - - + + + + + + + - + - + - + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + C C C C C C C M M C C N C N C M M C C N C N C N M N C C C C - - + + + + - - + + - - - + + + - + + - + - - - + + + + + + - - 12, GGT->GAT 12, GGT->GTT - 12, GGT->TGT - - - 13, GGC->GAC - - - - - - - - - - - - - - - - 12, GGT->GAT - 12, GGT->AGT - Abbreviations: DI: DNA index C:cytoplasmic, M:membraneous, N:nuclear Of the 30 rectal cancers investigated herein, 3 showed MSI, which is higher than the 1–2% MSI detected in larger series of rectal cancers, but lower than the 15% MSI tu- mors observed among sporadic colorectal cancers. This finding indicates that the frequency of MSI in young pa- tients with rectal cancer is considerably lower than the 17–58% MSI tumors and 20–40% HNPCC-causing muta- tions reported in mixed series of colorectal cancers from young patients [5–10,14,18]. All three MSI tumors identi- fied in our study displayed immunohistochemical loss of MSH2 expression. Whereas immunohistochemical loss of MLH1 may reflect either a germline mutation or somatic hypermethylation of the MLH1 promoter, loss of MSH2 expression is almost exclusively caused by a germline mu- tation of the MSH2 gene [12,19,20]. Thus, hypermethyla- tion of MLH1 plays a limited role in rectal cancers from young patients, which is in accordance with an associa- tion between MLH1 hypermethylation and proximal tu- mors, older patients and female sex [13]. Consequently, the finding of MSI in a rectal cancer is, together with a family history of the disease, a strong indicator of HN- PCC. Although HNPCC-associated tumors show a pre- diliction for the proximal colon about 40% of HNPCC- associated tumors will develop in the distal colon or with- in the rectum. Mutations in codons 12 and 13 of KRAS are found in about 1/3 of colorectal tumors [21,22]. These mutations develop early in colorectal tumor progression [23]. The prognostic value of KRAS mutations is somewhat unclear, but a recent study compiling data from over 3000 patients with colorectal cancer, did in a multivariate analysis dem- onstrate a significant impact on survival by the codon 12 glycine alanine mutation, which is found in about 9% of the tumors [24]. We identified KRAS mutations in 6/30 rectal cancers (Table 3). All mutations were heterozygous missense mutations of types that have previously been de- scribed, and one patient displayed the codon 12 glycine Page 6 of 8 (page number not for citation purposes)