Understanding NTRK Fusions in Premalignant Colorectal Lesions
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.