You are here

Article Text

Article menu
Download PDFPDF
Original research
IHC versus FISH versus NGS to detect ALK gene rearrangement in NSCLC: all questions answered?
  1. Ullas Batra1,
  2. Shrinidhi Nathany2,
  3. Mansi Sharma1,
  4. Sunil Pasricha3,
  5. Abhishek Bansal4,
  6. Parveen Jain1,
  7. Anurag Mehta5
  1. 1 Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
  2. 2 Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
  3. 3 Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
  4. 4 Radiology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
  5. 5 Laboratory Services, Transfusion Medicine and Research, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
  1. Correspondence to Dr Ullas Batra, Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi 110085, India; ullasbatra{at}gmail.com

Abstract

Aims Anaplastic lymphoma kinase (ALK) rearranged non-small cell lung carcinoma (NSCLC) is a distinct molecular subtype and rapid approval of ALK tyrosine kinase inhibitors (TKIs) has necessitated rapid and sensitive diagnostic modalities for the detection of this alteration. Gene rearrangements can be identified using many techniques including fluorescence in situ hybridisation (FISH), reverse transcriptase-PCR, next-generation sequencing (NGS) and immunohistochemistry (IHC) for fusion oncoprotein expression. We aimed to determine the concordance between IHC, FISH and NGS for ALK biomarker detection, and determine differences in sensitivity, and survival outcomes.

Methods We analysed the concordance between IHC using D5F3 monoclonal antibody, FISH (break-apart) and NGS using a custom panel containing 71 different ALK variants.

Results Among 71 cases included in this study, FISH was evaluable in 58 cases. The concordance of ALK IHC with FISH was 75.9% and that with NGS was 84.5%. The sensitivities of FISH and NGS were 75.6% and 87.5%, respectively. The median progression-free survival of ALK IHC-positive and FISH-negative group was 5.5 months and that of both positive was 9.97 months.

Conclusion Although NGS offers a better throughput and visualisation, IHC still remains the quintessential screening tool in upfront diagnosis of ALK rearranged NSCLC.

  • genes
  • neoplasm
  • lung neoplasms
  • immunohistochemistry
  • diagnostic techniques and procedures
  • medical oncology

Data availability statement

Data are available on reasonable request. All data relevant to the manuscript have been presented here. Any additional data required will be made available from the corresponding author on reasonable request.

https://doi.org/10.1136/jclinpath-2021-207408

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    Data are available on reasonable request. All data relevant to the manuscript have been presented here. Any additional data required will be made available from the corresponding author on reasonable request.

    View Full Text

    Footnotes

    • Handling editor Runjan Chetty.

    • Contributors All authors have contributed to the conductance of the study and preparation of this manuscript, as well all authors have reviewed the final manuscript.

    • Funding This work was supported by an educational grant funded by Pfizer Products India Private Limited (Number: 63631449).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.