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Published ahead of print on February 20, 2003, doi:10.1164/rccm.200211-1297OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 12, June 2003, 1670-1675

A more recent version of this article appeared on June 15, 2003
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Submitted on November 7, 2002
Accepted on February 17, 2003

Detection of Telomerase Expression in Mediastinal Lymph Nodes of Patients with Lung Cancer

Michael B Wallace1*, Mark Block2, Brenda J Hoffman1, Robert H Hawes1, Gerard Silvestri3, Carolyn E Reed2, Michael Mitas2, James Ravenel4, Mostafa Fraig5, Scott Miller3, Edward T Jones3, and Alice Boylan3

1 Division of Gastroenterology, Digestive Disease Center, Medical University of South Carolina, Charleston, SC, USA, 2 Surgery, Medical University of South Carolina, Charleston, SC, USA, 3 Division of Pulmonary Medicine and Critical Care, MUSC and Ralph H Johnson VAMC, Medical University of South Carolina, Charleston, SC, USA, 4 Radiology, Medical University of South Carolina, Charleston, SC, USA, 5 Pathology, Medical University of South Carolina, Charleston, SC, USA

* To whom correspondence should be addressed. E-mail: wallacem{at}musc.edu.

Background: Mediastinal lymph nodes are the most common site of tumor spread in non-small cell lung cancer (NSCLC). We hypothesized that micrometastatic disease could be detected by rtPCR for expression of telomerase reverse transcriptase (hTERT) in mediastinal lymph nodes and that a minimally invasive technique (endoscopic ultrasound guided fine needle aspiration EUS-FNA) is capable of sampling lymph nodes for PCR analysis without surgery. Methods: Mediastinal lymph nodes were sampled with EUS-FNA in patients with NSCLC, and negative controls undergoing EUS for benign disease. Total RNA was harvested from samples and rtPCR was performed to detect telomerase gene expression. Results: RNA was available from 87/100 lymph node aspirates from 39 patients with NSCLC and from 12 negative control patients. hTERT was expressed in 0/14 negative control lymph nodes, in 18/57 pathologically negative lymph nodes from cancer patients, and in 10/16 pathologically positive lymph nodes (p<0.05). Five of 18 (28%) patients with no pathologically evident mediastinal disease expressed telomerase in at least one lymph node. Conclusions: Minimally invasive EUS-FNA with rtPCR is capable of detecting expression of cancer specific mRNA in lymph nodes. Approximately 1/3 of pathologically negative mediastinal lymph nodes in NSCLC patients express hTERT mRNA. The clinical significance of this observation is yet to be determined.
Key words: Non-small cell lung cancer, endoscopic ultrasound, staging, biomarkers, micrometastases




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