Biomarker NTRK Coverage from Every Angle
Advertisement
Advertisement

Understanding NTRK Fusions in Premalignant Colorectal Lesions

By: Joseph Fanelli
Posted: Wednesday, October 6, 2021

Research findings presented in medRxiv, the preprint server for health sciences prior to peer review, suggest that NTRK-rearranged colorectal tumors appear to develop exclusively through the serrated neoplasia pathway. These tumors include sessile serrated lesions, sessile serrated lesions with dysplasia, and sporadic microsatellite instability–high (MSI-H) colorectal cancers, concluded Gyeong Hoon Kang, MD, PhD, of the University College of Medicine, Seoul, and colleagues.

“NTRK fusions are a relatively early event that can occur morphologically prior to full dysplastic change and molecularly prior to MSI-H development in sessile serrated lesions,” the authors added.

In this study, the authors assessed pan-TRK expression by immunohistochemistry from tissue samples infected with colorectal epithelial tumors. The authors reviewed 441 colorectal cancer tumors (including 133 MSI-H cases and 308 MSI-stable cases) as well as 565 premalignant colorectal lesions (including 300 serrated lesions and 265 conventional adenomas).

The authors did not observe TRK positivity in any cases of microsatellite-stable colorectal cancers, conventional adenomas, traditional serrated adenomas, or hyperplastic polyps. TRK positivity was found in 11 of 58 sporadic MSI-H colorectal cancers (19%), 4 of 23 sessile serrated lesions with dysplasia (17%), and 5 of 132 sessile serrated lesions (4%). The authors noted that the 11 TRK-positive MSI-H colorectal cancer tissues all harbored CpG island methylator phenotype-high, MLH1 methylation, KRAS/BRAF wild-type genomes, and NTRK1 or NTRK3 fusions.

NTRK1 and NTRK3 rearrangements, as well as KRAS/BRAF wild-type genomes, were found in all nine TRK-positive sessile serrated lesions with dysplasia. The authors noted that TRK overexpression and early dysplastic changes are occasionally co-localized in the crypt base area of sessile serrated lesions. They also believe that age-related occurrence patterns may suggest that the progression interval of NTRK-rearranged sessile serrated lesions to colorectal cancer may be shorter than from BRAF-mutated sessile serrated lesions to colorectal cancer.

Disclosure: The authors reported no conflicts of interest.



By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.