Clinical significance of / for stage II/III sporadic colorectal cancer.

BACKGROUND

The development of colorectal cancer (CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes. In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes (MMR), among which and are the most important. Recently, numerous studies indicated that phenotype is associated with CRC. We wanted to elucidate the role of in the prediction and prognosis of CRC through long-term clinical observation.

AIM

To evaluate the prognostic and predictive significance of in patients with stage II-III CRC using immunohistochemical analysis and GeneScan.

METHODS

Specimens from 681 patients with CRC (395 stage II and 286 stage III, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested. Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis.

RESULTS

Five hundred and fifty (80.76%) patients were positive and 131 (19.24%) were negative by immunohistochemistry. -positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production ( < 0.05). Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin. -negative patients had a more favorable OS than -positive patients ( < 0.001). Univariate and multivariate analyses demonstrated expression as an independent prognostic and predictive factor for stage II/III CRC. expression was a strong prognostic factor in all patients [ < 0.001, hazard ratio (HR) = 4.064, 95%CI: 2.241-7.369]. Adjuvant chemotherapy had a greater correlation with survival advantage in -negative patients with stage III disease ( < 0.001, HR = 7.660, 95%CI: 2.974-15.883). However, patients with stage II disease or -positive patients with stage III disease did not benefit from adjuvant chemotherapy. GeneScan analysis demonstrated that among 133 patients, 105 (78.95%) were microsatellite stable, and 28 (21.05%) had microsatellite instability (MSI), including 18 (13.53%) with high MSI and 10 (7.52%) with low MSI. This is consistent with the immunohistochemical results.

CONCLUSION

phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC. is an independent prognostic and predictive factor for outcome of stage II-III CRC.