Inconsistent intersample alk fish results in patients with lung cancer: Analysis of potential causes

Zhenya Tang, Hui Chen, Lingzhi Hong, Guilin Tang, Gokce A. Toruner, Wei Wang, Sinchita Roy Chowdhuri, Wei Yin, Hai Suk Jung, Jun Gu, Mark J. Routbort, Jianjun Zhang, Joseph D. Khoury, L. Jeffrey Medeiros

Research output: Contribution to journalArticlepeer-review


ALK FISH analyses of multiple specimens occasionally yield inconsistent intersample results in lung cancer patients, posing clinical challenges requiring intensive analysis of all potential causative pre-and post-analytic factors. In this study, 19 patients (8M/11F) with inconsistent intersample ALK FISH results were analyzed, representing 4.9% of patients assessed ≥ twice in our institution. Fifteen patients received ALK tyrosine kinase inhibitor(s) (TKIs). Nine patients died, and ten were alive for 8 to 74-month follow-ups (median, 40 months). Through strict and stringent laboratory and case-review policies, all postanalytic factors were excluded. Correlating clinical information, ALK results obtained by RNA sequencing (RNA-seq) and other concurrent tests, several pre-analytic factors were determined. A suboptimal specimen was likely the cause in three patients, supported by the failure of one or more concurrent tests or discrepant results between FISH and RNA-seq. ALK inhibition by TKIs might have been responsible for the change of ALK status from positive to negative in eight patients. Other potential explanations include the existence of multiple primary lung cancer lesions, tumor heterogeneity, and the clonal evolution of tumor cells, related or not to ALK TKI therapy. This study is helpful for both pathologists and clinicians encountering inconsistent and/or discrepant intersample results.

Original languageEnglish (US)
Article number1903
Pages (from-to)1-17
Number of pages17
Issue number7
StatePublished - Jul 2020
Externally publishedYes


  • ALK
  • Fluorescence in situ hybridization (FISH)
  • Lung cancer
  • Next-generation sequencing (NGS)
  • RNA sequencing (RNA-seq)
  • Tyrosine kinase inhibitor (TKI)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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