PMID- 34033159 OWN - NLM STAT- MEDLINE DCOM- 20220118 LR - 20220118 IS - 1365-2303 (Electronic) IS - 0956-5507 (Linking) VI - 32 IP - 5 DP - 2021 Sep TI - Validation of ROS1 by immunohistochemistry against fluorescent in situ hybridisation on cytology and small biopsy samples in a large teaching hospital. PG - 621-630 LID - 10.1111/cyt.12994 [doi] AB - OBJECTIVE: Rearranged ROS1, present in 1%-2% of non-small cell lung cancer (NSCLC) patients, usually young, never or light smokers, is assessed by fluorescence in situ hybridization (FISH) to determine eligibility for tyrosine kinase inhibitors (TKI). Immunohistochemistry (IHC) for the protein product of ROS1 rearrangement, a cost-effective alternative, is validated on cytology and small biopsy samples. METHODS: From 1 March to 31 December 2019, cytology cell blocks and small biopsy samples from a selected cohort of NSCLC patients were concurrently tested for ROS1 gene rearrangement by Vysis 6q22 Break Apart FISH probe and IHC using Cell Signalling D4D6 antibody. Mismatch cases were tested by an RNA fusion next generation sequencing (NGS) panel. RESULTS: In a prospective population of 95 cases, 91 were negative and two were positive by both FISH and IHC. Both dual positive cases were female never smokers and benefited from TKI treatment. Another two cases were positive by FISH but negative by IHC and repeat by NGS showed one to be negative but one failed. Turnaround time for IHC was 0 to 8 days from request to authorisation, whilst that of FISH was 9 to 42 days at a cost of pound51 and pound159 respectively. CONCLUSION: IHC to assess for the protein product of ROS1 gene rearrangement on cytology cell blocks and small biopsy samples in a routine setting is a promising screening method to assess eligibility for TKI treatment with positive and indeterminate cases confirmed by FISH or NGS as it has good negative predictive value, faster turnaround time and is cost effective, with proven technical and clinical validation. CI - (c) 2021 John Wiley & Sons Ltd. FAU - Narine, Nadira AU - Narine N AUID- ORCID: 0000-0001-7563-329X AD - Manchester Cytology Centre, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Wallace, Andrew AU - Wallace A AD - Genomic Diagnostics Laboratory, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Dore, Jonathan AU - Dore J AD - Genomic Diagnostics Laboratory, Manchester University NHS Foundation Trust, Manchester, UK. FAU - O'Leary-Jackson, Simon AU - O'Leary-Jackson S AD - Manchester Cytology Centre, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Al Najjar, Haider AU - Al Najjar H AD - Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Bailey, Simon AU - Bailey S AD - Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Khan, Kashif AU - Khan K AD - Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Teng, Benjamin AU - Teng B AD - Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Qasim, Muhammad AU - Qasim M AD - Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Shelton, David AU - Shelton D AD - Manchester Cytology Centre, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Holbrook, Miles AU - Holbrook M AD - Manchester Cytology Centre, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Abbasi, Salma AU - Abbasi S AD - Department of Respiratory Medicine, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Carter, Matthew AU - Carter M AD - Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK. FAU - Irion, Luciane AU - Irion L AD - Department of Histopathology, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Al-Habba, Samer AU - Al-Habba S AD - Department of Histopathology, Manchester University NHS Foundation Trust, Manchester, UK. FAU - Lindsay, Colin AU - Lindsay C AD - Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK. FAU - Blackhall, Fiona AU - Blackhall F AD - Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK. FAU - Rana, Durgesh AU - Rana D AD - Manchester Cytology Centre, Manchester University NHS Foundation Trust, Manchester, UK. LA - eng GR - pound3000.00/Pfizer UK/ PT - Journal Article DEP - 20210615 PL - England TA - Cytopathology JT - Cytopathology : official journal of the British Society for Clinical Cytology JID - 9010345 RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (ROS1 protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biopsy/*methods MH - Carcinoma, Non-Small-Cell Lung/diagnosis/metabolism MH - Cytodiagnosis/*methods MH - Female MH - Hospitals, Teaching/methods MH - Humans MH - Immunohistochemistry/*methods MH - In Situ Hybridization, Fluorescence/*methods MH - Lung Neoplasms/diagnosis/metabolism MH - Male MH - Middle Aged MH - Prospective Studies MH - Protein-Tyrosine Kinases/*metabolism MH - Proto-Oncogene Proteins/*metabolism OTO - NOTNLM OT - FISH OT - IHC OT - ROS1 OT - biopsy OT - cell block OT - cytology EDAT- 2021/05/26 06:00 MHDA- 2022/01/19 06:00 CRDT- 2021/05/25 14:11 PHST- 2021/03/25 00:00 [revised] PHST- 2020/08/28 00:00 [received] PHST- 2021/04/26 00:00 [accepted] PHST- 2021/05/26 06:00 [pubmed] PHST- 2022/01/19 06:00 [medline] PHST- 2021/05/25 14:11 [entrez] AID - 10.1111/cyt.12994 [doi] PST - ppublish SO - Cytopathology. 2021 Sep;32(5):621-630. doi: 10.1111/cyt.12994. Epub 2021 Jun 15.