Published online May 28, 2016. doi: 10.3748/wjg.v22.i20.4936
Peer-review started: February 29, 2016
First decision: March 21, 2016
Revised: April 9, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: May 28, 2016
Processing time: 84 Days and 23.7 Hours
AIM: To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice.
METHODS: A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC genes.
RESULTS: Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF+ type with proximal location.
CONCLUSION: Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated (methylation) pathway.
Core tip: The results indicate that molecular subtyping from endoscopic biopsies is feasible in routine gastroenterology practice to evaluate a patient’s prognosis. Subtyping based on Jass classification can be used to evaluate molecular mechanisms of adenoma-carcinoma transition.