CLINICAL PATHOLOGICAL CHARACTERISTICS AND FREQUENCY OF ALK MUTATIONS IN NON-SMALL CELL LUNG CANCER (NSCLC)

Abstract

Abstract Introduction. Lung cancer is a malignant tumor origi-nating from the respiratory epithelium of the lungs: the alveolar epithelium and the epithelium of the tracheo-bronchial stem. It is the most common cause of death associated with malignant diseases in the world. The incidence of lung cancer varies depending on gender and race. It is twice as high in men, although in recent years there has been a significant decline in the inci-dence in men, while the rate in women has risen in the last decade. About 80-85% of all lung cancers are of the non-small cell lung cancer (NSCLC) type, while about 15% are small cell lung cancers. Smoking is the most common risk factor. In 5% of patients with NSCLC, an inversion of chromosome 2 consisting of a juxtaposition of the 5' end echinoderm microtubule asso-ciated with protein 4 (EML4) gene with a 3' end of ana-plastic lymph node with oncogene EML4-ALK is de-tected. Screening for this fusion gene in NSCLC is par-ticularly important because "ALK-positive" tumors are highly sensitive to targeted therapy with ALK inhibitors. Objectives. 1. To determine the distribution of non-small cell lung cancer (NSCLC) by gender and age, smoking status, histological subtype; 2. To determine the stage of the disease determined by radiological TNM classifica-tion; 3. To determine the frequency of ALK mutations in patients with NSCLC. Methods. This is a prospective study conducted at the PHI University Clinic for Pulmonology and Allergology and the Institute of Pathology, Faculty of Medicine - Skopje over a period of 1 year. In all patients included in the study, tissue samples obtained from lung biopsy (bronchobiopsy or transthoracic biopsy) were analyzed. The microscopic description included histological type ________________________

definition of the tumor and the degree of histological differentiation. The study also processed clinical pa-tient data and disease stage with radiological TNM cla-ssification (determined by contrast CT of the chest and mediastinum). To determine the mutation of the ALK gene, tissue samples were processed with FISH using an identical DNA probe. Conclusion. ALK mutations were noted in 3 of a total of 52 patients, or 5.77%, which was very close to the global trend of mutations of about 5%. Given the small sample of participants, it is possible that the general population of patients with NSCLC follows exactly the world trend. According to the available studies, screening with low-dose computed tomography of the lungs is recommended for all current heavy smokers or individuals who have smoked 15 or more years, aged 55 to 80 years. All this coincides with our research, in which most of the patients diagnosed with NSCLC were smokers and over 50 years of age. Keywords: NSCLC, ALK, TNM, EML4, histopathology