Clinicopathologic Features of Patients with Non-Small Cell Lung Cancer Harboring the EML4-ALK Fusion Gene: A Meta-Analysis

Abstract

BackgroundThe frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene.MethodsThe Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted.ResultsSeventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30–0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66–3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41–0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03–0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger's test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status.ConclusionThis meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR.

ALK Protein Analysis by IHC Staining after Recent Regulatory Changes: A Comparison of Two Widely Used Approaches, Revision of the Literature, and a New Testing Algorithm

“…A revision of the literature on FISH/IHC analysis-discordant cases, including our series (reported in Table 4) indicates a response rate of 100% and 46% for IHC analysis-positive (the Ventana test)/ FISH-negative and IHC analysis-negative (all tests)/ FISH-positive patients, respectively. 4,7,10,20,21,[23][24][25][26][27][28][29][30] These data indicate the important role of IHC analysis in the selection of patients for anti-ALK treatment. 31 To ensure that no ALK-positive patients are left behind, however, it would be desirable to carry out IHC and FISH analysis in all cases.…”

Characteristics and Outcomes of Patients with Lung Cancer Harboring Multiple Molecular Alterations: Results from the IFCT Study Biomarkers France

“…25 These data are concordant with the results of a meta-analysis conducted by Wang et al in which only 0.75% of patients (three of 399) with EGFR mutations also harbored ALK rearrangement. 26 However, numerous clinical cases (n ¼ 43) have been reported and collected in a recent review of case series, leading to the conclusion of a 1.5% prevalence for ALK rearrangement in patients with EGFR mutation. 27 In addition, Rosell et al reported on a population of 95 EGFR-mutated adenocarcinomas (EURTAC trial), with a 15.8% prevalence of concomitant ALK rearrangement, although this result was probably accounted for by the low specificity of the polymerase chain reaction assay.…”

Influence of Estrogen on the NSCLC Microenvironment: A Comprehensive Picture and Clinical Implications

“…This pathway serves as a target for small-molecule tyrosine kinase inhibitors (TKIs) such as erlotinib and osimertinib, which have become first-line treatment options for EGFR mutant NSCLC (15). Anaplastic lymphoma kinase (ALK) oncogene related translocations also occur more frequently in female NSCLC patients, presenting another welldefined drug target to clinicians (16,17). Likewise, the rare ROS1 rearrangements are also more common in lung ACs from women than men (18)(19)(20).…”