Correlation of the expression of mismatch repair proteins, CDX2, and SATB2 with the clinicopathological parameters of patients with colorectal carcinoma.

Mutations in mismatch repair (MMR) genes play a crucial role in the pathogenesis of colorectal carcinoma (CRC), accounting for 10% to 15% of sporadic cases and up to 90% of hereditary non-polyposis cases. Reduced expression of the two transcription factors CDX2 and SATB2 has been linked to poor patient survival. The primary objective of this study was to evaluate the expression of mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), along with CDX2 and SATB2, in relation to clinicopathologic characteristics and the survival outcome. The study included 97 CRC patients with colectomy specimens received in the Pathology Department at Mansoura University during the period from 2011 to 2015. Immunohistochemistry for MLH1, MSH2, MSH6, PMS2, CDX2, and SATB2 was applied to tissue microarrays constructed from the patients' paraffin blocks. Out of the 97 CRC patients examined, 38.1% (n = 37) showed MMR deficiency, whereas 61.9% (n = 60) showed intact MMR expression. Twenty-one cases showed combined loss of two proteins: MLH1/PMS2 (n = 15) and MSH2/MSH6 (n = 6), while 13 cases showed loss of only one protein. A significant correlation between MMR deficiency and the patient gender, the right-sided location, and the low score of tumor-budding was noted (p-values of 0.045, 0.002, and 0.001, respectively). The overall MMR deficiency showed no statistically significant association with SATB2 expression score, while isolated MSH2 deficiency showed a significant association with SATB2 expression (p = 0.004). The disease-free survival (DFS) and overall survival (OAS) showed no significant association with MMR deficiency, CDX2, and SATB2 expression scores. A shorter DFS was noted with older age and rectal location (p = , p = .,, respectively), while shorter OAS was noted with older age and high tumor-budding (p = 0.046, p = 0.001, respectively). The MMR deficiency showed a significant association with the male gender, the right-sided location, and the low score of tumor-budding, and this may influence the prognosis and management plans. The relation between loss of SATB2, CDX2, and MMR protein expression needs further studies to be validated as a potential pathogenetic mechanism and as promising therapeutic targets.