EMAST status as a beneficial predictor of fluorouracil-based adjuvant chemotherapy for Stage II/III colorectal cancer.

BACKGROUND:Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) is a type of microsatellite instability that occurs in ∼60% of colorectal cancers (CRCs) and associated with MSH3 dysfunction. A 5-fluorouracil (5-FU)-related cytotoxicity is attenuated in MSH3-deficient colon cancer cells. Reported here is the predictive value of EMAST in CRCs with Stage II or III disease treated with 5-FU-based chemotherapy. METHODS:EMAST status was analyzed in 157 patients with CRC with Stage II or III disease and MSH3 expression was analyzed using immunohistochemistry. The patients treated with 5-FU-based chemotherapy were studied in terms of the links of EMAST status with MSH3 expression, clinicopathological features, and overall survival (OS). RESULTS:A total of 63 patients (40.1%) had EMAST positive (EMAST⁺ ) CRC and 77 patients (49.0%) had low MSH3 expression. EMAST⁺ tumors were associated with advanced TNM stage and poor and moderately differentiated tumor. EMAST CRC was more frequently observed in tumors with low expression of MSH3 in the nucleus (n = 53; 84.1%, p < .001). On multivariate analysis, patients with EMAST⁺ status had a worse OS (hazard ratio: 2.489, 95% confidence interval [1.149-5.394], and p = .021). Worse OS in EMAST⁺ patients who received 5-FU-based chemotherapy was significantly more common compared with EMAST^- CRCs. CONCLUSION:There is a link between EMAST and reduced nuclear expression of MSH3. There is worse survival in patients with EMAST⁺ CRC after 5-FU-based chemotherapy. According to our findings, adjuvant 5-FU-based chemotherapy might not be advantageous in EMAST⁺ CRCs with Stage II or III disease.

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