title: Assessment of methylation status of locoregional lymph nodes in lung cancer using EBUS-NA.
abstract: Hypermethylation of the promoter region of tumor suppressor genes is associated with carcinogenesis in lung cancer (LC). Endobronchial ultrasound with needle aspiration (EBUS-NA) is a semi-invasive method for obtaining cell blocks from lymph nodes, which can be used for epigenetic analyses. To establish the relationship between methylation status of p16, DAPK, RASSF1a, APC and CDH13 genes in lymph nodes sampled by EBUS-NA, tumor staging and prognosis. Methylation status of DAPK, p16, RASSF1a, APC and CDH13 genes was assessed in EBUS-NA cell blocks from LC patients and related to stage and survival. Eighty-five consecutive patients [mean age 67 (SD 8)] were included. Methylation of ≥1 gene was found in 43 malignant nodes (67 %). A higher prevalence of RASSF1a methylation was observed in small cell lung cancer patients [9/10 (90 %) vs. 15/53 (28 %); p < 0.001 χ(2) test]. Methylation of APC and/or p16 was related to advanced staging in non-small cell lung cancer (NSCLC) [15/29 (52 %) vs. 6/24 (25 %), p = 0.048, χ(2) test]. Patients with NSCLC showing methylation of APC and/or p16 had also lower 6-month survival (p = 0.019, log rank test), which persisted after adjustment for age and subtyping (HR = 6, 95 % CI [1.8-19.5], p = 0.003, Cox regression). Epigenetic analyses are feasible in EBUS-NA cell blocks and may identify methylation patterns associated with worse prognosis. Methylation of p16 and APC genes in NSCLC patients was associated with advanced staging and lower 6-month survival.
authors.affiliation: Fundació Parc Taulí, Parc Taulí 1, Edificio Santa Fe Planta Baja, 08208, Sabadell, Barcelona, Spain. lmillares@tauli.cat.|CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain. lmillares@tauli.cat.|Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain. lmillares@tauli.cat.|Fundació Insitut d'Investigació Germans Trias i Pujol, Badalona, Spain. lmillares@tauli.cat.
authors.forename: Laura
authors.initials: L
authors.lastname: Millares
authors.affiliation: Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain.|Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Serra
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain.|Department of Respiratory Medicine, Hospital Universitario Germans Trias i Pujol, Badalona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Andreo
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain.|Department of Respiratory Medicine, Hospital Universitario Germans Trias i Pujol, Badalona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Sanz-Santos
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain.|Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Montón
authors.affiliation: Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Grimau
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain.|Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Gallego
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain.|Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Setó
authors.affiliation: Department of Pathology, Hospital Universitari Parc Taulí, Sabadell, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Combalia
authors.affiliation: Department of Pathology, Hospital Universitario Germans Trias i Pujol, Badalona, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Llatjos
authors.affiliation: Department of Pathology, Hospital Universitari Parc Taulí, Sabadell, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Escoda
authors.affiliation: Department of Pathology, Hospital Universitario Germans Trias i Pujol, Badalona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Castellà
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain.|Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain.|Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Monsó
mesh_terms: D000368:Aged; D001999:Bronchoscopy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration / Q000379:methods*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology
keywords: EBUS-NA; Lung cancer; Lymph nodes; Methylation; NSCLC