hTERT Gene Amplification and Clinical Significance in Pleural Effusions of Patients With Lung Cancer

The cytologic assessment of pleural effusions to distinguish carcinoma cells from reactive mesothelial cells is particularly challenging. We have, for the first time, used a quantitative polymerase chain reaction technique to detect hTERT (human telomerase reverse transcriptase) gene amplification in 115 pleural effusions and showed that this technique was more sensitive and could be a useful adjunct to cytology. In addition, it may be useful for an earlier diagnosis of pleural micrometastases. Patients and Methods: Human telomerase reverse transcriptase (hTERT) gene amplification was detected in pleural effusions of patients with lung cancer (n = 69) and in patients with benign lung disease (n = 46) when using a quantitative polymerase chain reaction (qPCR) technique. Results: hTERT gene relative copy numbers were significantly higher in effusions from patients with malignant, adenocarcinoma and small-cell lung cancer than in effusions from patients with benign lung disease (P<.01). By using a threshold value of 1.39, hTERT gene amplification was significantly more frequent in malignant effusions compared with benign effusions and more likely to be positive for malignant effusions, compared with cytology (P<.01). The diagnostic performance of qPCR of hTERT gene amplification was significantly higher than that of cytology, in terms of sensitivity (91.3% vs. 56.5%), negative predictive value (87.8% vs. 60.5%), and accuracy (92.2% vs. 73.9%). Conclusions: Detecting hTERT gene amplification by qPCR appears suitable for distinguishing carcinoma cells from reactive mesothelial cells in pleural effusions. hTERT gene amplification was more sensitive than cytology and may be useful for diagnosing pleural micrometastases.