Expression analysis of oncogene transcript in human Aberrant Crypt foci, in comparison to the normal colonic mucosa and colorectal carcinoma from formalin-fixed paraffin-embedded tissue samples: A Pilot Study

Abstract Purpose: Aberrant Crypt Foci (ACF) are microscopic preneoplastic lesions in human colon detectable by magnified chromoendoscopy. Our aim was to analyze the expression of a chosen gene transcript in harvested colonic ACF, corresponding colorectal carcinomas (CRC) and normal mucosa. Methods: A total of 35 cases having ACF >4 in number/ 4 mm2 colonic mucosa were selected from 302 fresh colectomy samples screened along with the corresponding CRC (35) and normal colonic mucosal shavings (20). Gene expression analysis was performed by reverse transcriptase-polymerase chain reaction in these 3-groups. The gene expression data were correlated with histological and topographical ACF types, lymph node metastasis, site, size, and stage of tumors. Results: The KRAS, CDKN1A, CDKN2A, MLH1, VEGFA, and CCL5 gene expressions were significantly altered in ACF compared to controls (p <0.01), while the genes CDNK2A, PTEN (p 0.01), and SMAD4 (p 0.05) were significantly altered in CRC than in controls. The gene expression profile of the mucosal ACF and corresponding CRC foci were similar. No definitive correlation was found between topographic and histological types of ACF and gene expressions. Up-regulation of IGF1 and EGFR genes in ACF were associated with higher lymph node metastases and larger tumor sizes respectively, while down-regulation of RB1 and Bcl2 genes were associated with smaller tumor size. Conclusions The molecular pathogenesis of ACF is as complex as that like advanced CRC foci. Our observation is fascinating as it brings forth the complex pathogenesis of these early mucosa lesions and defies sequential molecular accumulation hypothesis.