An alternative pathway in colorectal carcinogenesis based on the mismatch repair system and p53 expression in Korean patients with sporadic colorectal cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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 (p < 0.001), 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 (p < 0.001) and histology (p < 0.001). Comparison between G1 and G3 showed differences in location (p < 0.001) and histology (p < 0.001). Comparison between G2 and G4 showed differences in age (p < 0.001), location (p < 0.001), size (p = 0.006), histology (p < 0.001), node metastasis (p < 0.001), distant metastasis (p < 0.001), and stage (p < 0.001). On multivariate analysis, stage (p = 0.007) and histology (p < 0.001) were associated with improved overall survival, and stage (p < 0.001) was associated with disease-free survival.


CONCLUSIONS
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.
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hyoung Ran
HR
Kim
Hee Cheol
HC
Kim
Hae-Ran
HR
Yun
Seok Hyung
SH
Kim
Cheol Keun
CK
Park
Yong Beom
YB
Cho
Seong Hyeon
SH
Yun
Woo Yong
WY
Lee
Ho-Kyung
HK
Chun
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D056910:Republic of Korea; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein