An Alternative Pathway in Colorectal Carcinogenesis Based on the Mismatch Repair System and p53 Expression in Korean Patients with Sporadic Colorectal Cancer

Microsatellite instability (MSI) and chromosomal instability are main mechanisms underlying colorectal carcinogenesis. We determined the features and prognosis of colorectal cancer based on MSI including mismatch repair genes and expression of p53.Between 1999 and 2008, a total of 2,649 colorectal cancer patients were analyzed using a prospective database. A mismatch repair defect (MMR-D) was defined as a loss of expression of more than one MMR protein and/or MSI-high. MMR-proficiency (MMR-P) was defined as expression of all MMR proteins and microsatellite stable (MSS)/MSI-low. Groups 1 (G1), 2 (G2), 3 (G3), and 4 (G4) were defined as MMR-D and p53-positive expression, MMR-D and p53-negative expression, MMR-P and p53-positive expression, MMR-P and p53-negative expression, respectively.Eighty-two (3.0%), 181 (6.8%), 1,368 (51.7%), and 1,018 (38.5%) patients were classified into groups 1-4, respectively. Comparison between G1 and G2 showed differences in location (p0.001), size (p = 0.030), node metastasis (p = 0.027), distant metastasis (p = 0.009), and stage (p = 0.040). Comparison between G3 and G4 showed differences in location (p0.001) and histology (p0.001). Comparison between G1 and G3 showed differences in location (p0.001) and histology (p0.001). Comparison between G2 and G4 showed differences in age (p0.001), location (p0.001), size (p = 0.006), histology (p0.001), node metastasis (p0.001), distant metastasis (p0.001), and stage (p0.001). On multivariate analysis, stage (p = 0.007) and histology (p0.001) were associated with improved overall survival, and stage (p0.001) was associated with disease-free survival.According to the MSI and p53 subsets, colorectal cancers showed different clinicopathologic features, but these subsets had no prognostic impact on overall and disease-free survival rate.