Abstract
BackgroundAnaplastic Lymphoma Kinase (ALK) positivity represents a novel molecular target in a subset of Non-Small Cell Lung Cancers (NSCLC). We explore Fluorescence in situ Hybridization (FISH) and Immunohistochemistry (IHC) as diagnostic methods for ALK positive patients and to describe its prevalence and outcomes in a population of NSCLC patients.MethodsNSCLC patients previously screened for Epidermal Growth Factor Receptor (EGFR) at our institution were selected. ALK positive patients were identified by FISH and the value of IHC (D5F3) was explored.Resultsninety-nine patients were identified. Median age was 61.5 years (range 35–83), all were caucasians, eighty percent were adenocarcinomas, fifty-one percent were male and thirty-eight percent were current smokers. Seven (7.1%) patients were ALK positive by FISH, thirteen (13.1%) were EGFR mutant, and 65 (65.6%) were negative/Wild Type (WT) for both ALK and EGFR. ALK positivity and EGFR mutations were mutually exclusive. ALK positive patients tend to be younger than EGFR mutated or wt patients. ALK positive patients were predominantly never smokers (71.4%) and adenocarcinoma (71.4%). ALK positive and EGFR mutant patients have a better outcome than negative/WT. All patients with ALK FISH negative tumours were negative for ALK IHC. Out of 6 patients positive for ALK FISH with more tissue available, 5 were positive for ALK IHC and 1 negative.ConclusionsALK positive patients represent 7.1% of a population of selected NSCLC. ALK positive patients have different clinical features and a better outcome than EGFR WT and ALK negative patients. IHC is a promising method for detecting ALK positive NSCLC patients.
Highlights
Lung cancer is the most frequent cause of cancer-related death worldwide, accounting for more than 1 million deaths per year. [1] cytotoxic chemotherapy remains the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC), [2] the identification of specific genetic lesions which drive proliferation of cancer cells has led to the development of new target therapies in a subset of patients with Non-Small Cell Lung Cancers (NSCLC) [3,4]
[1] cytotoxic chemotherapy remains the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC), [2] the identification of specific genetic lesions which drive proliferation of cancer cells has led to the development of new target therapies in a subset of patients with NSCLC [3,4]
The aim of this study is to explore the prevalence of Anaplastic Lymphoma Kinase (ALK) positivity in a European cohort of selected NSCLC patients by Fluorescence in situ Hybridization (FISH), to better define its clinical features and outcomes and, to explore IHC as diagnostic method testing for ALK in NSCLC patients
Summary
Lung cancer is the most frequent cause of cancer-related death worldwide, accounting for more than 1 million deaths per year. [1] cytotoxic chemotherapy remains the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC), [2] the identification of specific genetic lesions which drive proliferation of cancer cells has led to the development of new target therapies in a subset of patients with NSCLC [3,4]. [1] cytotoxic chemotherapy remains the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC), [2] the identification of specific genetic lesions which drive proliferation of cancer cells has led to the development of new target therapies in a subset of patients with NSCLC [3,4]. Anaplastic lymphoma kinase (ALK) rearrangement, predominantly with the echinoderm microtubuleassociated protein like 4 (EML4) gene, has been identified as an oncogenic event in a subset of NSCLC patients [4]. Results of a phase 1 trial evaluating an ALK inhibitor, Crizotinib, in patients with ALK positive NSCLC demonstrated encouraging results [6]. Clinical trials with Crizotinib and other ALK inhibitors in this subset population of ALK positive NSCLC patients are ongoing. Anaplastic Lymphoma Kinase (ALK) positivity represents a novel molecular target in a subset of Non-Small Cell Lung Cancers (NSCLC). We explore Fluorescence in situ Hybridization (FISH) and Immunohistochemistry (IHC) as diagnostic methods for ALK positive patients and to describe its prevalence and outcomes in a population of NSCLC patients
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