Telomerase activity in transthoracic fine needle biopsy aspirates as a marker of peripheral lung cancer

Abstract

Background: A study was undertaken to evaluate the usefulness of telomerase activity assay in transthoracic fine needle biopsy (TFNB) aspirates collected from peripheral tumours of the lung in predicting the malignant aetiology of lung infiltrations. Methods: 100 patients with a peripheral infiltration of the lung underwent TFNB of the focal lesion. The aspirates were subjected to standard cytological evaluation. Telomerase activity in the specimens was determined with the PCR-ELISA PLUS method. The sensitivity, specificity, accuracy and predictive value of TFNB were calculated for cytological examination of aspirates alone and cytological examination with additional telomerase activity assessment. Results: Lung cancer was newly diagnosed in 84 subjects and benign peripheral lesions were found in 16. During the first TFNB, lung cancer was identified in 56 cases of cancer (66.7%) while increased telomerase activity was found in 61 cancer aspirates (72.6%). No subject with a benign infiltration had a false positive result from cytological examination, but in one case (6.25%) increased telomerase activity was observed. The diagnostic sensitivity, accuracy and negative predictive value of the combination of cytological examination and telomerase activity assay in TFNB specimens were significantly higher than for cytological examination alone (89.3% vs 66.7%, p = 0.0004; 90% vs 72%, p = 0.001; 62.5% vs 36.4%, p = 0.039), but a combination of the two examinations was associated with a lower specificity of TFNB (96.9% vs 100%, p = 0.002). Conclusion: Detection of telomerase activity in aspirates taken during TFNB of a peripheral lung infiltration should be considered as an indication of the risk of malignancy in cases with false negative cytological results.

Detection of telomerase activity in cultured cells and tumor tissue of lung carcinoma by modified telomeric repeat amplification protocol

“…Using the TRAP-PAGE or TRAP-ELISA assay with the CX or ACX reverse primer, telomerase activity was reported 70-73% in bronchial lavage, 75% in transthoracic fine needle biopsy aspirates and 82.5% in pleural effusions of malignant patients whereas 6.25-19.3% false positivity in benign samples. [16][17][18][19][20][21] Since our modified TRAP assay could ignore the inference on telomerase activity from hundred-fold somatic cells, frozen tissues were directly grinded and extracted for telomerase with no necessity of cancer cell capture techniques, such as microdissection. Among sixty lung carcinoma cases, the realtime PCR TRAP demonstrated a positive telomerase activity in 51 samples (85%), in contrast to 47 (78%) cases by TRAP-PAGE.…”

“…For example, telomerase activity assessment in cytological specimens has been used in the differential diagnosis of malignant and benign focal lesions of the lung. Using the TRAP‐PAGE or TRAP‐ELISA assay with the CX or ACX reverse primer, telomerase activity was reported 70–73% in bronchial lavage, 75% in transthoracic fine needle biopsy aspirates and 82.5% in pleural effusions of malignant patients whereas 6.25–19.3% false positivity in benign samples 16–21 . Since our modified TRAP assay could ignore the inference on telomerase activity from hundred‐fold somatic cells, frozen tissues were directly grinded and extracted for telomerase with no necessity of cancer cell capture techniques, such as microdissection.…”

Telomerase activity and serum levels of p53 protein as prognostic factors of survival in patients with advanced non-small cell lung cancer

“…2,22 In our previous studies we proved that assessment of telomerase activity in lung infiltrations is a useful supplemental procedure in differentiation between malignant and benign tumours. 23 It is thought then that telomerase, as an enzyme responsible for unlimited replication of genetic material inside cancer cells and incomplete cell divisions, could be a molecular prognostic factor. Fujita et al 24 observed that strong and moderate expression of human telomerase reverse transcriptase mRNA (hTERT) in resected NSCLC was a prognostic factor of survival with predictive power similar to that of lymph node status, pathomorphological TNM stage and the age of patients.…”

Increased Survivin mRNA in Malignant Pleural Effusion is Significantly Correlated with Survival

“…Various adjuvant methods have been proposed, including determining specific tumor markers (4), protein telomerase (5) and chromosome analysis (6). However, there are no currently reliable and effective molecular biomarkers used in diagnosing and predicting outcome for cancer patients.…”