PMID- 37142453 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240418 IS - 1878-3562 (Electronic) IS - 1590-8658 (Linking) VI - 55 IP - 12 DP - 2023 Dec TI - Elaboration of NTRK-rearranged colorectal cancer: Integration of immunoreactivity pattern, cytogenetic identity, and rearrangement variant. PG - 1757-1764 LID - S1590-8658(23)00578-9 [pii] LID - 10.1016/j.dld.2023.04.019 [doi] AB - Fused information from protein status, DNA breakage, and transcripts are still limited because of the low rate of activated-NTRK in colorectal cancer (CRC). In total, 104 archived CRC tissue samples with dMMR were analyzed using immunohistochemistry (IHC), polymerase chain reaction (PCR), and pyrosequencing to mine the NTRK-enriched CRC group, and then subjected to NTRK fusion detection using pan-tyrosine kinase IHC, fluorescence in situ hybridization (FISH), and DNA-/RNA-based next generation sequencing (NGS) assays. Of the 15 NTRK-enriched CRCs, eight NTRK fusions (53.3%, 8/15), including two TPM3(e7)-NTRK1(e10), one TPM3(e5)-NTRK1(e11), one LMNA(e10)-NTRK1(e10), two EML4(e2)-NTRK3(e14), and two ETV6(e5)-NTRK3(e15) fusions, were identified. There was no immunoreactivity for ETV6-NTRK3 fusion. In addition to cytoplasmic staining found in six specimens, membrane positive (TPM3-NTRK1 fusion) and nuclear positive (LMNA-NTRK1 fusion) were also observed in two of them. Atypical FISH-positive types were observed in four cases. Unlike IHC, NTRK-rearranged tumors appeared homogeneous on FISH. ETV6-NTRK3 may be missed in pan-TRK IHC screening for CRC. Regarding break-apart FISH, NTRK detection is difficult because of the diversity of signal patterns. Further research is warranted to identify the characteristics of NTRK-fusion CRCs. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Wu, Shafei AU - Wu S AD - Department of Pathology, Peking Union Medical College Hospital, Molecular Pathology Research Center, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730,China. FAU - Liu, Yuanyuan AU - Liu Y AD - Department of Pathology, Peking Union Medical College Hospital, Molecular Pathology Research Center, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730,China. FAU - Shi, Xiaohua AU - Shi X AD - Department of Pathology, Peking Union Medical College Hospital, Molecular Pathology Research Center, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730,China. FAU - Zhou, Weixun AU - Zhou W AD - Department of Pathology, Peking Union Medical College Hospital, Molecular Pathology Research Center, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730,China. FAU - Zeng, Xuan AU - Zeng X AD - Department of Pathology, Peking Union Medical College Hospital, Molecular Pathology Research Center, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing 100730,China. Electronic address: zengxuan88@yahoo.com. LA - eng PT - Journal Article DEP - 20230502 PL - Netherlands TA - Dig Liver Dis JT - Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver JID - 100958385 RN - 0 (Biomarkers, Tumor) RN - 9007-49-2 (DNA) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (Receptor, trkC) SB - IM MH - Humans MH - Biomarkers, Tumor/genetics/analysis MH - *Colorectal Neoplasms/genetics MH - DNA MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - *Receptor, trkA/genetics/analysis MH - Receptor, trkB/genetics MH - Receptor, trkC/genetics OTO - NOTNLM OT - Colorectal carcinoma OT - Fluorescence in situ hybridization OT - Immunohistochemistry OT - NTRK fusion OT - Next generation sequencing COIS- Conflicts of interest The other authors declare no conflicts of interest. EDAT- 2023/05/05 00:42 MHDA- 2023/12/17 09:42 CRDT- 2023/05/04 21:57 PHST- 2023/02/01 00:00 [received] PHST- 2023/04/13 00:00 [revised] PHST- 2023/04/17 00:00 [accepted] PHST- 2023/12/17 09:42 [medline] PHST- 2023/05/05 00:42 [pubmed] PHST- 2023/05/04 21:57 [entrez] AID - S1590-8658(23)00578-9 [pii] AID - 10.1016/j.dld.2023.04.019 [doi] PST - ppublish SO - Dig Liver Dis. 2023 Dec;55(12):1757-1764. doi: 10.1016/j.dld.2023.04.019. Epub 2023 May 2.