Impact of microsatellite status on chemotherapy for colorectal cancer patients with or mutation.

and mutations are frequently detected in cases of colorectal cancer (CRC). The microsatellite status of patients with CRC and mutated / is important when determining cancer therapy. In the present study, the microsatellite status and genetic polymorphisms of (codons 12 and 13) and (V600E) were characterized in CRC tissue. The mismatch repair activity and oncogenic potential of were assessed by immunoblots from two -mutated CRC cell lines, SW480 and HCT116, with different microsatellite statuses, following treatment with 5-fluorouracil (5-FU) and oxaliplatin. Of all the 205 patients with CRC enrolled in the present study, 31.2% (64 of 205) had a or mutation, and 79.7% (51 of 64) of these patients with a / mutation exhibited microsatellite stability (MSS), indicating that microsatellite status is correlated with / mutation (P=0.027). A higher proportion (39.0%, 41 of 105) of elderly patients (≥62.6 years) had mutated or than younger patients (<62.6 years; 23.0%, 23 of 100; P=0.013). In the subgroup of 154 patients with MSS, patients without the or mutation (n=110) had longer disease-specific survival rates (58.8±9.4%) than patients with or mutations (n=44; 50.6±11.0%; P=0.043). Cytoplasmic KRAS levels decreased whereas nuclear MutS protein homolog 2 (MSH2) levels increased slightly in CRC HCT116 cells that were microsatellite instable, following treatment with 76.9 µM 5-FU for 2 days. In microsatellite stable SW480 cells, MSH2 levels markedly increased in the nucleus following 150 µM oxaliplatin treatment for 3 days. However, no significant change was observed regarding KRAS distribution in these cells. The results of the present study suggest that it is important to identify patients with CRC who may benefit from adjuvant chemotherapy with 5-FU or oxaliplatin, particularly CRC patients with MSS and mutated or , who have poorer overall survival rates than patients with microsatellite instability. Knowledge of the microsatellite status of patients and whether they harbor or mutations may enable more effective therapeutic strategies to be developed. Further prospective studies are required to validate the findings of the current study.