Premium
EMAST status as a beneficial predictor of fluorouracil‐based adjuvant chemotherapy for Stage II/III colorectal cancer
Author(s) -
Mohammadpour Somayeh,
Goodarzi Hamed R.,
Jafarinia Mojtaba,
Porhoseingholi Mohammad A.,
NazemalhosseiniMojarad Ehsan
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29249
Subject(s) - medicine , microsatellite instability , oncology , colorectal cancer , chemotherapy , fluorouracil , stage (stratigraphy) , cancer , microsatellite , gene , allele , biology , paleontology , biochemistry
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.