Prognostic impact of telomerase activity in non-small cell lung cancers

Abstract

Objective: To evaluate the clinical significance of telomerase activity, particularly in terms of prognostic impact, in non-small cell lung cancer (NSCLC).

Summary background data: Telomerase activity has been found in various tissues. The activation of telomerase is considered necessary for the immortalization of human tumor cells, including NSCLC.

Methods: The authors studied 103 NSCLC specimens using a polymerase chain reaction based on a telomeric repeat amplification protocol assay.

Results: Telomerase activity was detected in 85 (82.5%) of 103 NSCLC specimens but in none of the paired normal lung tissue specimens. More cases of positive telomerase activity were observed in the group with advanced disease and in the group with poorly differentiated tumors. Such factors as the mean age at surgery, sex, smoking, histologic type, and size of tumor extension did not correlate with the telomerase activity. The Kaplan-Meier survival curves in all patients with NSCLC demonstrated that patients with telomerase-positive tumors survived for a significantly shorter period than those with a telomerase-negative tumor (p = 0.0058). According to a multivariate analysis, telomerase activity was identified as an independent prognostic factor (RR = 8.62, p = 0.035).

Conclusions: Telomerase activity was one of the most important prognostic factors in patients with NSCLC, and its potential prognostic implication was independent of tumor stage.

Figure 1. Telomerase activity in NSCLC. T, tumor; N, normal lung tissue; L, only lysis buffer; 10, extract from 10 cells of telomerase-positive lung cancer cell line; 100, extract from 100 cells of lung cancer cell line. TRAP assay was performed using 6 μg protein extract. This figure is a composite of three different autoradiographs displaying variations of some banding patterns due to a slight variation in electrophoresis conditions. (A) Telomerase-negative tumor. (B,C) Telomerase-positive adenocarcinomas. (D,E) Telomerase-positive squamous cell carcinomas. (F,G,H) Telomerase-negative tumors, including an internal telomerase assay standard. (I) A telomerase-positive tumor including RNase (+), not including RNase (−).

Figure 2. Survival curves of patients with NSCLC. (A) Comparison between the telomerase-positive (n = 85) and telomerase-negative (n = 18) groups. Patients with telomerase-positive tumors have a significantly poorer prognosis than those with telomerase-negative tumors (generalized Wilcoxon test, p = 0.0058). (B) Comparison between the telomerase-positive (n = 32) and telomerase-negative (n = 9) group in patients with stage I tumors (generalized Wilcoxon test, p = 0.201). No patient with telomerase-negative tumor has died.