Validation of ROS1 by immunohistochemistry against fluorescent in situ hybridisation on cytology and small biopsy samples in a large teaching hospital

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Nadira Narine
  • Andrew Wallace
  • Jonathan Dore
  • Simon O'Leary-Jackson
  • Haider Al Najjar
  • Simon Bailey
  • Kashif Khan
  • Benjamin Teng
  • Muhammad Qasim
  • David Shelton
  • Miles Holbrook
  • Salma Abbasi
  • Matthew Carter
  • Luciane Irion
  • Samer Al-Habba
  • Durgesh Rana

Abstract

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 £51 and £159 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.

Bibliographical metadata

Original languageEnglish
JournalCytopathology : official journal of the British Society for Clinical Cytology
Early online date25 May 2021
DOIs
Publication statusE-pub ahead of print - 25 May 2021