Mechanisms of oncogenesis in colon versus rectal cancer

Abstract

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 beta-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 beta-catenin expression (p=0.75). Rectal cancers showed significantly more nuclear beta-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 beta-catenin in the APC/beta-catenin pathway than colon cancer and/or nuclear beta-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.

Possible alternative carcinogenesis pathway featuring microsatellite instability in colorectal cancer stroma

“…Furthermore, we found a difference in the relation between p53 mutations and stromal MSI (stromal MSI þ /p53 mutation, 3/11 (27%) in the left-side; 3/4 (75%) in the right-side, P ¼ 0.0952). These results support the conclusion of Kapiteijn et al (2001) and suggest a relation of p53 mutation to stromal MSI þ .…”

“…Recently, Kapiteijn et al (2001) reported that p53 gene mutation corresponds more often to p53 overexpression in left-than in right-sided tumours, suggesting that mechanisms of oncogenesis may differ between the two cases. This is in line with our results for a greater prevalence of p53 overexpression with p53 gene mutations in left-sided tumours (9/11, 81%), than in those found on the right side (1/4, 25%) (P ¼ 0.0390, data not shown).…”

Colon cancer surgery following emergency presentation: effects on admission and stage-adjusted outcomes

“…A second issue that makes the findings of previous work hard to interpret specifically for colon cancer is the lack of differentiation that all but 2 14,15 of the discussed articles make between colon and rectal disease -an issue shared with many publications on the matter. [19][20][21] Malignancies of the colon and rectum have been shown to be quite different in tumor biology 22 and subsequent prognosis 23 and arguments to split both are a recurring issue in outcome studies. 24 Our work is therefore the first to review a large cohort of colon cancer-specific patients in a single center.…”

Reduced fructosamine-3-kinase activity and its mRNA in human distal colorectal carcinoma

“…For these reasons, it is important to rid proteins of their sugar adducts rather than replace them with newly synthesized macromolecules. Different studies have demonstrated a better clinical outcome for the patients with proximal colorectal cancer with respect to distal colorectal cancer [2,11]. Colonic cells of proximal colon appear to have more efficient mechanisms to protect their proteins against the glycating effects of high glucose or fructose compared to distal colon cells.…”