Significance of EGFR signaling pathway genetic alterations in radically resected non-small cell lung cancers from a Polish cohort. One institutional study

Purpose: We evaluated the distribution and clinical impact of EGFR, KRAS and HER2 copy number gains and EGFR, KRAS and BRAF activating mutations in resected non-small cell lung cancers (NSCLCs) from 151 Polish patients.

Materials and methods: Quantitative PCR and DNA sequencing were used for copy number evaluation and mutational analysis, respectively.

Results: An increased EGFR CN was found in 21.2% of the tumors, more commonly of the non-squamous histology (P=0.029), larger in size (P=0.004) and those obtained from women (P=0.040). HER2 copy gain was observed in 21.8% of the patients, more frequently with lymph node metastases (P=0.048) and stage IIIA disease (P=0.061). KRAS gain was found in 29.3% of the tumors, and was not associated with patients' clinicopathological features. No BRAF mutations were found. EGFR and KRAS mutation frequency and associations with clinicopathological characteristics did not differ significantly from those previously described for the NSCLC patients of Caucasian ethnicity. Strong associations existed between most of the analyzed alterations. In the multivariate model, EGFR mutations constituted an independent prognostic factor of the disease recurrence in adenocarcinoma patients (HR 7.20; 95%CI 1.31-39.48; P=0.023), while an increased EGFR copy number tended to indicate a shorter overall survival (HR 4.85; 95%CI 0.92-25.58; P=0.062).

Conclusions: EGFR pathway genes alterations are frequent in NSCLCs from Polish patients and have a prognostic potential for patients' clinical outcome after a curative tumor resection. Gene CN evaluation by quantitative PCR provides comparable results and enables assay standardization, yet the optimal scoring system needs to be developed.