Abstract

e20514 Background: Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers and remains the most commonly diagnosed human neoplasm with a poor prognosis. Significantly improving the clinical course of NSCLC, EGFR tyrosine kinase inhibitors are effective only against tumors carrying activating mutations in the EGFR gene, and their frequency varies depending on the patient population. The aim of the study was to analyze a retrospective group of Crimean patients with advanced NSCLC for the presence of EGFR gene aberrations and association with clinical outcome. Methods: We used DNA samples from FFPE blocks of tumor and non-tumor tissues of 72 European-type patients (aged 46-78 years, median 64 years, 82% - men, 18% - women) diagnosed with lung cancer (T1-1aN0-2M0-1, stage I-IV). The relative copy number of the EGFR gene was assessed by RT-qPCR using GAPDH and B2M as reference genes. Mutations (9 deletions in exon 19, L858R, T790M, L861Q, G719S/A/C, 3 insertions in exon 20, S768I) in the EGFR gene were determined using the Therascreen EGFR RGQ PCR Kit (Qiagen, Germany). Results: For Crimean population patients, the squamous subtype of NSCLC was more common (57%). EGFR copy number evaluation in patients with adenocarcinoma showed locus amplification in 9 patients (30%), no loss of copy number was recorded. In the squamous cell carcinoma group, locus amplification prevailed in 25 of 42 samples (59.6%) and a decrease in copy number was noted in 4 samples (9.5%). Differences in the frequency of aberrant changes in the relative copy number of EGFR in adenocarcinoma and squamous cell lung cancer groups were statistically significant (χ2 = 11.04 at p = 0.003). The activating mutation frequency in adenocarcinoma samples was 9.7% (ex19del), which was lower than the frequency recorded in European adenocarcinoma patient populations (14.4%, p = 0.036). No EGFR mutations were found in cases of squamous cell lung cancer. The presence of mutations and/or changes in EGFR copy number were associated with shorter overall survival in patients who did not receive targeted and immune therapy (p = 0.034). Conclusions: The ex19del activating mutation of the EGFR gene frequency in adenocarcinoma samples was 9.7%. A more frequent EGFR alteration was detected when assessing the locus copy number in the tumor relative to the non-tumor tissue: changes were recorded for 30% of adenocarcinoma cases and 69.1% of squamous cell lung cancer.

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