Purpose: Colorectal cancers develop through various mechanisms such as chromosomal instability, DNA mismatch repair deficiency (microsatellite instability), and epigenetic DNA promoter methylation (CpG island methylator phenotype). This study evaluated the disparity in neoplastic changes between colon and rectal cancers.
Methods: A clinic-based colorectal frozen tumor bank at a single institution was queried for colon and rectal adenocarcinomas. Tumor DNA was extracted and analyzed for microsatellite instability, methylation, and mutations in the oncogenes KRAS and BRAF. Patient demographics, tumor characteristics, and clinical outcomes were compared.
Results: The 268 patients with colon cancer and 89 with rectal cancer were similar in gender, tumor size, stage, and differentiation. Colon cancers had a higher incidence of microsatellite instability (27 percent) and methylator phenotype (28 percent) compared with rectal cancers (7 percent, 3 percent, respectively; P < 0.001). Although KRAS mutation rate was similar, colon cancers had a higher incidence of BRAF mutations (16.7 percent vs. 0 percent; P < 0.001). Microsatellite stable tumors had an increased risk of disease recurrence compared with microsatellite unstable tumors (odds ratio, 3.86). Despite overall differences in outcome between colon and rectal cancers, no significant difference in survival existed when similar molecular phenotypes were compared across anatomic sites.
Conclusions: Although colon cancers are molecularly heterogeneous, rectal cancers arise mostly via a single neoplastic pathway. Genetic and molecular differences influence prognosis more than anatomic location and suggest that oncogenic pathways contribute to survival differences between colon and rectal cancers.