Tumour samples from 73 CRC patients who were treated in advanced stage with either irinotecan alone or in combination with 5-FU/leucovorin, were analysed for expression of Bcl-2, hMLH1 and hMSH2 using immunohistochemistry.
We analyzed sporadic CRCs in Omani (of African origin, N = 61), Iranian (of Caucasian origin, N = 53) and African American (N = 95) patients for microsatellite instability, expression status of mismatched repair genes (hMLH1, hMSH2) and presence of the BRAF (V600E) mutation.
Tumour samples from 73 CRC patients who were treated in advanced stage with either irinotecan alone or in combination with 5-FU/leucovorin, were analysed for expression of Bcl-2, hMLH1 and hMSH2 using immunohistochemistry.
Moreover, a multivariate analysis revealed that hMLH1 mRNA expression was a significant independent prognostic factor for tumor recurrence in CRC patients treated with adjuvant 5-FU.
WNT signaling pathway dysregulation is an important event in the pathogenesis of colorectal cancer (CRC) with APC mutations seen in more than 80% of sporadic CRC.
Although relatively high folate intake was not associated with overall colorectal cancer risk, it reduced the risk of APC(-)colon tumors in men (RR 0.58, 95% CI 0.32-1.05, P(trend) = 0.06 for the highest vs. lowest tertile of folate intake).
We sequenced the MLH1/MSH2 coding and promoter core regions in CRC patients diagnosed below age 40, and/or with multiple primary cancers or familial cancer clustering suggestive of HNPCC, and correlated deleterious mutations with clinical and tumour features.
These results indicate that there are different oncogenic pathways in the MSI sporadic colorectal cancers with germline missense mutations in the hMSH2 gene.
Prevalence of MLH1/MSH2 mutations in CRC families was significantly increased by the presence of: (i) fulfilled Amsterdam criteria; (ii) four or more CRCs; or (iii) one or more endometrial cancer.
We suggest that the I1307K mutation may contribute to CRC in Israeli Arabs and that inactivating mutations of MSH2 and MLH1 may not be a major cause for early onset CRC.
Prevalence of MLH1/MSH2 mutations in CRC families was significantly increased by the presence of: (i) fulfilled Amsterdam criteria; (ii) four or more CRCs; or (iii) one or more endometrial cancer.
In order to assess the role of these genes in sporadic RER+ colorectal carcinoma, we have carried out a mutation analysis of MSH2 and MLH1 by two-dimensional (2-D) DNA electrophoresis, including heteroduplexing and separation in a denaturing gradient.