PMID- 32420065 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220414 IS - 2218-6751 (Print) IS - 2226-4477 (Electronic) IS - 2218-6751 (Linking) VI - 9 IP - 2 DP - 2020 Apr TI - Novel ALK-specific mRNA in situ hybridization assay for non-small-cell lung carcinoma. PG - 257-268 LID - 10.21037/tlcr.2020.03.04 [doi] AB - BACKGROUND: A recent technical advance in mRNA in situ hybridization (mRNA-ISH) assays provides simultaneous signal amplification and background suppression with a unique probe design that enables single-molecule visualization. We assessed the utility of the mRNA-ISH assay as a diagnostic tool for detecting anaplastic lymphoma receptor tyrosine kinase (ALK) mRNA in non-small-cell lung carcinoma (NSCLC). We compared the mRNA-ISH assay with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). METHODS: The study included 279 surgically resected lung adenocarcinomas and 44 transbronchial-biopsied (TBB) adenocarcinomas. mRNA-ISH was conducted using the RNAscope 2.0 system, which includes pre-designed probes for detecting the tyrosine kinase domain encoded in ALK mRNA. IHC was conducted on all 323 samples using ALK-specific antibodies. mRNA-ISH was performed on 279 surgical samples and 6 TBB samples. Break-apart FISH was used to examine samples that were mRNA-ISH-positive or IHC-positive. RESULTS: ALK protein expression was detected in 11 of 279 specimens (3.9%). ALK mRNA was also detected with mRNA-ISH in ALK-positive samples, and 9 of the 11 specimens (81%) were also positive for ALK using break-apart FISH. Using the IHC results as a reference, the sensitivity and specificity of mRNA-ISH was 100%. In the TBB cohort, ALK protein expression was observed in 3 of 44 specimens (6.8%), in which ALK mRNA expression was also detected. CONCLUSIONS: The ALK mRNA-ISH data were highly correlated with the IHC data, and ALK mRNA-ISH detected ALK mRNA expression in every FISH-positive sample. We conclude that mRNA-ISH could serve as an alternative or complementary method for diagnosing ALK rearrangements in NSCLC. CI - 2020 Translational Lung Cancer Research. All rights reserved. FAU - Hirai, Noriko AU - Hirai N AD - Respiratory Center, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Sasaki, Takaaki AU - Sasaki T AD - Respiratory Center, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Okumura, Shunsuke AU - Okumura S AD - Respiratory Center, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Sado, Masatoshi AU - Sado M AD - Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Akiyama, Naoko AU - Akiyama N AD - Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Kitada, Masahiro AU - Kitada M AD - Respiratory Center, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. AD - Breast Disease Center, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Takei, Hidehiro AU - Takei H AD - Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. FAU - Ohsaki, Yoshinobu AU - Ohsaki Y AD - Respiratory Center, Asahikawa Medical University, Asahikawa, Hokkaido, Japan. LA - eng PT - Journal Article PL - China TA - Transl Lung Cancer Res JT - Translational lung cancer research JID - 101646875 PMC - PMC7225155 OTO - NOTNLM OT - Anaplastic lymphoma receptor tyrosine kinase (ALK) OT - fluorescence in situ hybridization (FISH) OT - immunohistochemistry (IHC) OT - lung adenocarcinoma OT - mRNA in situ hybridization (mRNA-ISH) COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr.2020.03.04). The authors have no conflicts of interest to declare. EDAT- 2020/05/19 06:00 MHDA- 2020/05/19 06:01 PMCR- 2020/04/01 CRDT- 2020/05/19 06:00 PHST- 2020/05/19 06:00 [entrez] PHST- 2020/05/19 06:00 [pubmed] PHST- 2020/05/19 06:01 [medline] PHST- 2020/04/01 00:00 [pmc-release] AID - tlcr-09-02-257 [pii] AID - 10.21037/tlcr.2020.03.04 [doi] PST - ppublish SO - Transl Lung Cancer Res. 2020 Apr;9(2):257-268. doi: 10.21037/tlcr.2020.03.04.