MYC and Human Telomerase Gene (TERC) Copy Number Gain in Early-stage Non–small Cell Lung Cancer

• DOI: 10.1097/coc.0000000000000012
• Publication Date: 2013-11-26T03:00:21Z
• Authors: Antonella Flacco; Vienna Ludovini; Fortunato Bianconi; Mark Ragusa; Guido Bellezza; Francesca R. Tofa...; Lorenza Pistola; Annamaria Siggillino; Jacopo Vannucci; Lucio Cagini; Angelo Sidoni; Francesco Puma; Marileila Varella...; Lucio Crinò
• Keywords: Adult; Male; Lung Neoplasms; Gene Dosage; Genes, myc; Kaplan-Meier Estimate; Disease-Free Survival; 03 medical and health sciences; 0302 clinical medicine; Carcinoma, Non-Small-Cell Lung; Humans; FISH; MYC; non-small cell lung cancer; prognosis; TERC;; In Situ Hybridization, Fluorescence; Aged; Neoplasm Staging; Proportional Hazards Models; Retrospective Studies; Aged, 80 and over; FISH; MYC; non-small cell lung cancer; prognosis; TERC; Middle Aged; 3. Good health; ROC Curve; Area Under Curve; RNA; Female

We investigated the frequency 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 clinicopathologic parameters and outcome.Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) 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 squamous cell carcinoma (SCC) histology (P=0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P=0.032 [UCCC criteria] or P=0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival 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.