ALK Immunohistochemistry for ALK Gene Rearrangement Screening in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

Our results suggested that ALK IHC equivocal (score 1+ and 2+) cases should not be considered as IHC-negative in screening for ALK gene rearrangement. Additional detailed criteria for ALK IHC equivocal cases are necessary to determine how to best apply this approach in daily practice.

Outcomes According to ALK Status Determined by Central Immunohistochemistry or Fluorescence In Situ Hybridization in Patients With ALK-Positive NSCLC Enrolled in the Phase 3 ALEX Study

“…20 Furthermore, in a large systematic review and meta-analysis including 11,806 NSCLC cases from 42 individual studies, the concordance rate between ALK IHC and FISH in patients with ALK IHCpositive disease was 80.5% (95% CI: 73.3-86.1). 21 We found that the HR for investigator-assessed PFS was 0.37 (95% CI: 0.25-0.56) in patients with ALK IHCpositive and FISH-positive disease, which is consistent with the primary ITT analysis of ALEX (stratified HR ¼ 0.47, 95% CI: 0.34-0.65, p < 0.001). 2 The HR of 0.37 is consistent with that reported in the open-label, randomized phase 3 J-ALEX study of alectinib versus crizotinib in Japanese patients with advanced NSCLC, which required patients to have tumors that were both ALK IHC-positive and FISH-positive at enrollment (HR ¼ 0.34, 99.7% CI: 0.17-0.71).…”

Clinicopathological significance and diagnostic approach of ROS1 rearrangement in non-small cell lung cancer: a meta-analysis: ROS1 in non-small cell lung cancer

“…35,36 Taken together, an IHC panel including ALK, c-MET, and ROS1 can be useful for screening genetic alterations in NSCLC. [35][36][37][38][39][40] However, the clinical usefulness and diagnostic accuracy of ROS1 IHC is not fully understood. The present study is the first meta-analysis to assess the ROS1 rearrangement rate and the diagnostic accuracy of ROS1 IHC in NSCLC.…”

“…According to our results, the ROS1 IHC negative cases could be considered as negative for rearrangement without additional molecular testing, such as for c-MET and ALK IHC in NSCLC. 35,36 Therefore, ROS1 IHC can be useful for screening ROS1 rearrangement in NSCLC. However, the concordance rate between ROS1 IHC and molecular tests in ROS1 IHC positive cases was lower than that in ROS1 IHC negative cases.…”

Anaplastic lymphoma kinase immunohistochemistry scores do not predict sensitivity to crizotinib in fluorescence in situ hybridization-positive non-small cell lung cancer patients

“…To the editor: We read with interest the meta-analysis by Pyo et al in which the concordance between anaplastic lymphoma kinase (ALK) immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in ALK-positive non-small cell lung cancer was evaluated. 1 By gathering studies that investigated ALK FISH-positive rates according to the ALK IHC score using a four-tiered system, the FISH-positive rates for ALK IHC scores of 0, 1+, 2+, and 3+ were 0.009, 0.378, 0.628, and 0.900 by the random-effects model, respectively. This suggests that equivocal cases (score 1+, and 2+) should undergo confirmatory FISH.…”