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Telomerase Activity and Bcl-2 Expression in Non-Small Cell Lung Cancer

Department of Surgery II, Okayama University School of Medicine, Okayama, 700-8558 Japan

Bcl-2 and p53 are the most relevant proteins in apoptosis and tumor development. Telomerase functions in the maintenance of telomeres and is indispensable for immortalization. Bcl-2 was reported as a direct modulator of telomerase activity, and a correlation between p53 and telomerase activity was reported. The aim of this study was to determine the relationships between Bcl-2, p53, and telomerase activity in non-small cell lung cancer.

Immunostaining for Bcl-2, p53, and Ki-67 was performed in 64 surgically resected non-small cell lung cancers, and a fluorescence-based telomeric repeat amplification protocol assay for semiquantitative analysis of telomerase activity was done. Twenty-eight (44%) and 33 (52%) cases showed positive staining for Bcl-2 and p53, respectively. Bcl-2 expression was associated with negative lymph node involvement (P = 0.0248). p53 expression was associated with tumor size (P = 0.0244), p stage (P = 0.0391), and proliferative activity (P = 0.0004). Telomerase activity was detected in 89.1% and was closely associated with aggressive clinicopathological features. Telomerase activity was higher in p53-positive tumors (P < 0.0001), but represented no correlation with Bcl-2 expression (P = 0.3239). Interestingly, when the cases were stratified by histological grade and the level of Ki-67 labeling index, Bcl-2 expression was more clearly associated with favorable clinicopathological features and lower telomerase activity only in low-grade tumors.

In conclusion, p53 is closely associated with telomerase activity. In low-grade tumors, Bcl-2 is inversely correlated to telomerase activity. Our results suggest that the biological role of the Bcl-2 protein alters according to tumor aggressiveness, thereby cofunctioning with telomerase against genetic instability.