We evaluated the feasibility of using molecular markers to detect nonesmall-cell lung cancer (NSCLC) lymph node metastasis in endobronchial ultrasound-guided transbronchial needle aspiration samples. Thirty-three NSCLC patients and 17 control subjects were included. Cytokeratin-19, carcinoembryonic antigen, and epithelial cell adhesion molecule identified NSCLC lymphatic involvement. This might be important to improve the negative predictive value and accurately subtype these samples. Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) holds promise for accurate examination of mediastinal lymph nodes in NSCLC patients. However, it is not always possible to achieve a definitive diagnosis or subtype all cases. We aimed to evaluate the role of EBUS-TBNA combined with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry (FCM) to assess tumor-associated antigens and immune responses to identify metastases and pathological patterns in lymph node aspirates. Patients and Methods: EBUS-TBNA samples from patients with NSCLC (n = 33) and nonmalignant diseases (n 17) were prospectively collected. Cytokeratin 19 (CK-19), carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EPCAM), sialyl-Lewisx, CD44, and the immune compartment were analyzed using qRT-PCR and FCM. Results: In the NSCLC patients, the epithelial cell compartment was significantly increased (30.8\% vs. 12\% CD45(-) CK-19(+) cells) and showed brighter CK19 staining than controls (P=.039) using FCM. Carcinoembryonic antigen was exclusively expressed by the NSCLC epithelial compartment (35\% of the cases) and absent in controls. The NSCL Cimmune compartment showed an increased monocyte population (P=.04), and decreased lymphocyte subpopulations, anticipating a disruption in the distribution of myeloid and lymphoid immune cells. Quantitative reverse transcription polymerase chain reaction showed that CK-19, CEA, and EPCAM transcripts were significantly higher in NSCLC. A positive correlation between the primary tumor lesion size and EPCAM (rho=0.476; P=.005), CK-19 (rho=0.594; P=.001), and CEA (r=0.394; P=.023) was also found. Conclusion: The identification of CK-19, CEA, and EPCAM in EBUS-TBNA samples using FCM and qRT-PCR is feasible and might further aid in the detection of NSCLC lymph node metastasis.
Videira, P., Nunes, G., Almeida, A. B. D., Silva, Z., Correia, M. G., Martins, C., ... Gomes, M. J. M. (2013). Cytokeratin 19, Carcinoembryonic Antigen, and Epithelial Cell Adhesion Molecule Detect Lung Cancer Lymph Node Metastasis in Endobronchial Ultrasound-Guided Transbronchial Aspiration Samples. Clinical Lung Cancer, 14(6), 704-712. https://doi.org/10.1016/j.cllc.2013.06.004