Objective: Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) is a prognostic biomarker in colorectal cancer (CRC). EMAST phenotype appears to be linked to deficiency in DNA mismatch repair (MMR) proteins including MSH3. The TGF-β signaling pathway has a pivotal role in tumorigenesis of CRC. Since the biological causes of EMAST phenomenon has remained a matter of debate, this study aimed to investigate the association between Smad-dependent canonical signaling TGF-β pathway and EMAST phenotype in colorectal cancer patients.

Patients and Methods: EMAST status was analyzed in normal and paraffin-embedded tumor tissues of 122 CRC patients using QIAxcel capillary PCR and electrophoresis. Immunohistochemical method was used to determine the expression of canonical TGFβ-signaling pathway and MSH3 proteins. Eventually, the relationship between canonical TGF-β signaling pathway activation and EMAST phenotype and, therefore, MSH3 expression, was evaluated.

Results: 40.2% of CRC tumors had EMAST+ phenotype. The canonical TGF-β signaling pathway was activated in 27.9% of patients. Furthermore, 43.4% of patients indicated low expression of MSH3. 64.7% of tumors characterized with activated canonical TGF-β signaling pathway were EMAST+. Finally, a significant relationship between TGF-ß signaling pathway activation and MSH3 expression was observed.

Conclusions: In current study, the activation of canonical TGF-β signaling pathway in CRC tumors mediated by Smad proteins was significantly associated with EMAST phenotype and MSH3 expression.