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Assessment of methylation status of locoregional lymph nodes in lung cancer using EBUS-NA

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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 χ2 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, χ2 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.

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Acknowledgments

We thank Michael Maudsley for providing an outline for this manuscript and support in editing and journal styling. This work has been supported by Fondo de Investigación Sanitaria 09/01612, Sociedad Española de Neumología y Cirugía Torácica (SEPAR), Fundació Catalana de Pneumologia (FUCAP) and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES). CIBERES is an initiative of Instituto de Salud Carlos III.

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  1. Fundació Parc Taulí, Parc Taulí 1, Edificio Santa Fe Planta Baja, 08208, Sabadell, Barcelona, Spain

    Laura Millares

  2. CIBER de Enfermedades Respiratorias (CIBERES), Bunyola, Spain

    Laura Millares, Felipe Andreo, Jose Sanz-Santos, Concepción Montón, Miguel Gallego, Laia Setó & Eduard Monsó

  3. Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain

    Laura Millares, Mireia Serra & Eduard Monsó

  4. Fundació Insitut d’Investigació Germans Trias i Pujol, Badalona, Spain

    Laura Millares

  5. Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain

    Mireia Serra, Concepción Montón, Carles Grimau, Miguel Gallego, Laia Setó & Eduard Monsó

  6. Department of Respiratory Medicine, Hospital Universitario Germans Trias i Pujol, Badalona, Spain

    Felipe Andreo & Jose Sanz-Santos

  7. Department of Pathology, Hospital Universitari Parc Taulí, Sabadell, Spain

    Neus Combalia & Rosa Escoda

  8. Department of Pathology, Hospital Universitario Germans Trias i Pujol, Badalona, Spain

    Mariona Llatjos & Eva Castellà

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Millares, L., Serra, M., Andreo, F. et al. Assessment of methylation status of locoregional lymph nodes in lung cancer using EBUS-NA. Clin Exp Metastasis 32, 637–646 (2015). https://doi.org/10.1007/s10585-015-9733-2

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