P-126 * PROGNOSTIC SIGNIFICANCE OF MYC AND HUMAN TELOMERASE GENE AMPLIFICATION IN SURGICALLY TREATED EARLY STAGE NON-SMALL CELL LUNG CANCER

We investigated the incidence of MYC and TERC increased gene copy number (GCN) in early stage non-small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathological parameters and outcome. Tumour tissues were obtained from 113 NSCLC patients who were subjected to curative pulmonary resection. Median age was 66 years (range 40–84); most patients were male (84%), former/current smokers (92%), had poorly differentiated histology (42%) and stage I disease (62%). The histological types included 51% squamous cell carcinoma (SCC), 30% adenocarcinoma, 8% BAC, and 11% of other subtypes. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) using commercial probes according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification. When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥2.83 copies/cell) and TERC (mean ≥2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with SCC histology (P = 0.001). In univariate analyses, increased MYC GCN was associated with shorter overall survival (OS) (P = 0.032 (UCCC criteria) or P = 0.02 (ROC classification), while high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse OS using both the UCCC criteria (P = 0.02) and the ROC classification (P = 0.008). Our results confirm MYC as frequently amplified in early stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology. All authors have declared no conflicts of interest.