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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 reverse transcription-polymerase chain reaction (RT-PCR) for expression of human telomerase reverse transcriptase (hTERT) in mediastinal lymph nodes and that a minimally invasive technique (endoscopie ultrasound-guided fine-needle aspiration [EUS-FNA]) is capable of sampling lymph nodes for PCR analysis without surgery. Mediastinal lymph nodes were sampled with EUS-FNA in patients with NSCLC and negative control subjects undergoing EUS for benign disease. Total RNA was harvested from samples, and RT-PCR was performed to detect telomerase gene expression. RNA was available from 87 of 100 lymph node aspirates from 39 patients with NSCLC and from 12 negative control patients. hTERT was expressed in 0 of 14 negative control lymph nodes in 18 of 57 pathologically negative lymph nodes from cancer patients and in 10 of 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. Minimally invasive EUS-FNA with RT-PCR is capable of detecting expression of cancer specific mRNA in lymph nodes. Approximately one-third of pathologically negative mediastinal lymph nodes in NSCLC patients express hTERT mRNA. The clinical significance of this observation is yet to be determined.
Keywords: non-small cell lung cancer; staging; biomarkers; endoscopic ultrasound; micrometastases
Non-small cell carcinoma of the lung (NSCLC) is the most common cause of cancer death in the United States (1). The most common sites of tumor metastases are the lymph nodes in the mediastinum. Patients with involvement of mediastinal lymph nodes are at higher risk of failure from surgical resection alone and are generally treated with radiochemotherapy (2, 3). Non-invasive imaging methods such as computed tomography (CT) and positron emission tomography have imperfect accuracy for detecting mediastinal lymph node involvement but may be useful in guiding where to obtain pathologic confirmation. Approximately 20% of patients with a "normal" CT of the mediastinum eventually have malignant mediastinal adenopathy detected at surgery (4). Better preoperative staging may reduce this rate of unnecessary surgical exploration and morbidity.
Endoscopic ultrasound (EUS) is a minimally invasive guidance mechanism that is capable of sampling mediastinal lymph nodes by a transesophageal approach by fine-needle aspiration...