PMID- 33402590 OWN - NLM STAT- MEDLINE DCOM- 20220603 LR - 20220614 IS - 1998-4774 (Electronic) IS - 0019-509X (Linking) VI - 59 IP - 1 DP - 2022 Jan-Mar TI - FISH patterns of ROS1, MET, and ALK with a correlation of ALK immunohistochemistry in lung cancer: a case for introducing ALK immunohistochemistry 'Equivocal' interpretation category in the Ventana anti-ALK (D5F3) CDx assay - A tertiary cancer center experience. PG - 18-25 LID - 10.4103/ijc.IJC_470_19 [doi] AB - BACKGROUND: Mutations in ROS1, ALK, and MET genes are targetable alterations in non-small cell lung cancer (NSCLC). They can be evaluated by different techniques, most commonly fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). METHODS: We explored the prevalence of ROS1, ALK, MET mutations, discuss clinicopathological associations and FISH signal patterns on 413 consecutive cases of EGFR negative lung carcinoma from March 2016 to April 2017 using FISH for ALK, ROS1, and MET along with ALK (D5F3) IHC. RESULTS: ROS1 gene rearrangement, ALK positivity (IHC and/or FISH), and MET amplification were seen in 18/358 (5%) cases, 76/392 cases (19.4%), and 10/370 (2.7%) cases, respectively. ALK FISH and ALK IHC were positive in 51/300 (17%) and 58/330 cases (17.57%), respectively, while 8/330 (2.4%) cases were ALK IHC "equivocal" of which 3/8 (37.5%) were ALK FISH positive. Of ALK FISH and IHC co-tested cases, 43/238 (18.07%) cases were positive by both techniques, while 15/43 (34.88%) of ALK positive cases showed discordant ALK FISH and IHC results. All ROS1 rearranged and MET amplified cases were adenocarcinoma. Signet ring cell histology was associated with 78.57% likelihood of being either ALK or ROS1 positive. Genomic heterogeneity was seen in 30% of MET amplified cases. CONCLUSIONS: ALK/ROS1/MET gene alterations were found in 25.18% of NSCLC cases. An ALK IHC "equivocal" interpretation category should be incorporated into practice. Atypical patterns of ROS1 and genomic heterogeneity need to be evaluated further for any clinical relevance. FAU - Singh, Angad AU - Singh A AD - Division of Molecular Pathology, Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India. FAU - Kumar, Rajiv AU - Kumar R AD - Division of Molecular Pathology, Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India. FAU - Shetty, Omshree AU - Shetty O AD - Division of Molecular Pathology, Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India. FAU - Desai, Sangeeta AU - Desai S AD - Division of Molecular Pathology, Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India. FAU - Rane, Swapnil AU - Rane S AD - Division of Molecular Pathology, Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India. LA - eng PT - Journal Article PL - India TA - Indian J Cancer JT - Indian journal of cancer JID - 0112040 RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (ROS1 protein, human) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Anaplastic Lymphoma Kinase MH - *Carcinoma, Non-Small-Cell Lung/diagnosis/genetics MH - Gene Rearrangement/genetics MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence/methods MH - *Lung Neoplasms/diagnosis/genetics/pathology MH - Protein-Tyrosine Kinases/genetics MH - Proto-Oncogene Proteins/genetics MH - Proto-Oncogene Proteins c-met MH - Receptor Protein-Tyrosine Kinases/genetics OTO - NOTNLM OT - ALK rearrangement OT - MET amplification OT - ROS1 rearrangement OT - fluorescence in situ hybridization OT - lung adenocarcinoma COIS- None EDAT- 2021/01/07 06:00 MHDA- 2022/06/07 06:00 CRDT- 2021/01/06 05:39 PHST- 2021/01/07 06:00 [pubmed] PHST- 2022/06/07 06:00 [medline] PHST- 2021/01/06 05:39 [entrez] AID - 301403 [pii] AID - 10.4103/ijc.IJC_470_19 [doi] PST - ppublish SO - Indian J Cancer. 2022 Jan-Mar;59(1):18-25. doi: 10.4103/ijc.IJC_470_19.