PT  - JOURNAL ARTICLE
AU  - Laura Millares
AU  - Guadalupe Bermudo
AU  - Laia Setó
AU  - Carles Grimau
AU  - Neus Combalia
AU  - Maria Rosa Escoda
AU  - Eva Castellà
AU  - Mariona Llatjos
AU  - Felipe Andreo
AU  - Jose Sanz
AU  - Concepcion Monton
AU  - Miguel Gallego
AU  - Eduard Monsó
TI  - Methilation status in EBUS-NA samples of lung cancer
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P339
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P339.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P339.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Introduction: Aberrant methylation of DNA causes gene silencing and is frequent in lung cancer (LC). Epigenetic changes contribute to tumour progression and the identification of methylated genes in mediastinal metastasis by non-invasive techniques may improve LC characterization.Objective: To determine the relationships between methylation status of 5 genes in samples obtained by endobronchial ultrasound with needle aspiration (EBUS-NA) and LC type and stage.Methods: Samples obtained with EBUS-NA from patients with peripheral LC were flash-frozen with N2, DNA was extracted and chemically modified, and methylation status of DAPK, p16, RASSF1, APC and CDH13 genes was determined by methylation-sensitive high resolution melting.Results: 85 patients (67 SD 8 years), 37 (44%) with adenocarcinoma (ADC), 27 (32%) with squamous cell carcinoma (SCC), 12 (14%) with small cell LC (SCLC), and 8 (9%) with undifferentiated non-small cell LC, were included. ≥1 genes were methylated in 41/67 samples of mediastinal metastasis (67%) (61 node / 6 tumour). APC gene appeared methylated more often in ADC (13/31 (42%) vs 6/36 (17%); p= 0.022), and RASSF1 gene in SCLC samples (10/11 (91%) vs 16/56 (29%), p‹ 0.001). APC methylation was more often observed in advanced stage (stage IIIb-IV), than in patients with limited stage (I-IIIa) ADC (11/19 (58%) vs 2/12 (17%), p= 0.023).Conclusion: Gene methylation status may be assessed in mediastinal samples obtained by non-invasive endoscopic techniques. ADC was associated with APC methylation whereas SCLC with RASSF1 methylation. In ADC, the identification of APC methylation in mediastinal nodes or tumours was associated with advanced stage.Funded FIS 09/01612 and SEPAR.