MMR Gene Expression Pattern in Sporadic Colorectal Cancer

Abstract

Background and aims: Colorectal carcinoma is the second leading cause of death by cancer in Europe as its incidence increases with life span. Continuing research to detect new highly sensitive and specific noninvasive biomarkers is essential. The aim of this study was to compare 9 mismatching repair (MMR) genes activation levels in normal, polyp and malignant tissues in order to detect a MMR gene expression pattern in sporadic colorectal malignant pathology.

Methods: MMR mRNA levels were evaluated in tumor - normal tissue paired samples and polyps collected from 29 patients undergoing standard surgical procedures with curative intention. Real-Time quantitative Reverse Transcription PCR (qRT PCR) with TaqMan probes specific to ANKRD17, EXO1, MLH1, MLH3, MSH2, MSH3, MSH4, MSH5, MSH6 gene transcripts were used.

Results: The general tendency observed was a lower mRNA level of MMR genes in tumor samples compared with the normal tissue, with the exception of EXO1 gene. The number of patients that showed a higher expression of MMR genes in normal tissue was significantly greater than the number of patients that showed a higher expression inside the tumor (p=0.0024). ANKRD17 mRNA levels were higher in normal tissue than in tumor for 16 cases, by contrast with only 6 cases of higher mRNA levels in tumor.

Conclusions: ANKRD17 mRNA appears to be the most sensitive target and may have a potential value as an additional marker for the existing multitarget assay panel for colorectal cancer detection.