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.
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.
Authors: Yu-Wei Cheng; Hanna Pincas; Manny D Bacolod; Gunter Schemmann; Sarah F Giardina; Jianmin Huang; Sandra Barral; Kamran Idrees; Sajid A Khan; Zhaoshi Zeng; Shoshana Rosenberg; Daniel A Notterman; Jurg Ott; Philip Paty; Francis Barany Journal: Clin Cancer Res Date: 2008-10-01 Impact factor: 12.531
Authors: J Young; B Leggett; C Gustafson; M Ward; J Searle; L Thomas; R Buttenshaw; G Chenevix-Trench Journal: Hum Mutat Date: 1993 Impact factor: 4.878
Authors: Simon A Forbes; David Beare; Prasad Gunasekaran; Kenric Leung; Nidhi Bindal; Harry Boutselakis; Minjie Ding; Sally Bamford; Charlotte Cole; Sari Ward; Chai Yin Kok; Mingming Jia; Tisham De; Jon W Teague; Michael R Stratton; Ultan McDermott; Peter J Campbell Journal: Nucleic Acids Res Date: 2014-10-29 Impact factor: 16.971
Authors: Paul Lochhead; Aya Kuchiba; Yu Imamura; Xiaoyun Liao; Mai Yamauchi; Reiko Nishihara; Zhi Rong Qian; Teppei Morikawa; Jeanne Shen; Jeffrey A Meyerhardt; Charles S Fuchs; Shuji Ogino Journal: J Natl Cancer Inst Date: 2013-07-22 Impact factor: 13.506
Authors: Shailesh M Advani; Pragati Advani; Stacia M DeSantis; Derek Brown; Helena M VonVille; Michael Lam; Jonathan M Loree; Amir Mehrvarz Sarshekeh; Jan Bressler; David S Lopez; Carrie R Daniel; Michael D Swartz; Scott Kopetz Journal: Transl Oncol Date: 2018-07-30 Impact factor: 4.243
Authors: Shailesh Mahesh Advani; Pragati Shailesh Advani; Derek W Brown; Stacia M DeSantis; Krittiya Korphaisarn; Helena M VonVille; Jan Bressler; David S Lopez; Jennifer S Davis; Carrie R Daniel; Amir Mehrvarz Sarshekeh; Dejana Braithwaite; Michael D Swartz; Scott Kopetz Journal: BMC Cancer Date: 2019-10-17 Impact factor: 4.430