Frequency of ALK gene rearrangement and its association with survival rate among Upper Egypt Non-Small cell lung cancer patients

Abstract

Background: Anaplastic Lymphoma Kinase(ALK)gene rearrangement shows ethnic variations worldwide. There isn’t a population-based study measuring its prevalence among the Egyptian population till now. Aim: To measure ALK gene rearrangement prevalence correlated with survival rates among a sample of Upper Egypt Non-Small Cell Lung Cancer (NSCLC) patients. Patients and Methods: The study included twenty-six NSCLC patients. 21 of them were males and the rest were females, the enrolled patients had a median age of 60 years. 8 presented with pleural effusion, while 4 showed brain metastases, and 10 had liver metastases. Most of the cases were given a diagnosis with adenocarcinoma, squamous cell carcinoma (14, 6 cases, respectively), and the rest were given a diagnosis with undifferentiated carcinoma. Fluorescence Insitu Hybridization (FISH) technique was used for detection of rearranged ALK gene from FFEP Tissue Sections. Vysis ALK Break Apart FISH Probe Kit was used, it’s composed of two probes green-labeled one to bind to the 5′ end of the ALK gene, and another orange labeled one to bind to the 3′ end. Tumor cells with 15 % or more separate green 5′ and red 3′ signals or isolated red 3′ signals were considered positive for the rearranged ALK gene, while cells with yellowish signals (representing overlapped signals between green and red probes) were considered negative for ALK gene rearrangement. A fluorescence microscope supplied with a Leica CCD camera was used to detect clinicopathological characteristics of rearranged ALK gene, image processing was done using an imaging system and software. Results: Patients were followed up for 63 months, 15 of them were positive for the rearranged ALK gene. All patients were treated with chemotherapy and they had different objective response rates (ORR), ALK+ve cohort 73.3% (PR:3, SD:8), ALK–ve cohort 100% (PR:6, SD:5). The overall survival rate (OSR) was 51,6%, and two- year progression-free survival rate (PFSR) was 68,8%. Univariate analysis was done between ALK+ve / ALK–ve for different risk groups (age, gender, histological subtype, the site of metastasis, and grade). Patients with adenocarcinoma showed better OSR than those with squamous cell carcinoma, PConclusions: Patients with ALK gene rearrangement are resistant to chemotherapy, so they should be directed for individualized treatment, the prevalence of ALK+ve patients could be more than expected among the Egyptian population. further confirmation is required through multiple center population-based studies. Policymakers are invited for validating central laboratory, they are also recommended to enhance accessibility for diagnostic facilities and services, and adopting inhibitors of tyrosine kinase (TKI) as a new effective treatment strategy for NSCLC cases.