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Cooperative Role of Telomerase Activity and p16 Expression in the Prognosis of Non–Small-Cell Lung Cancer

From the Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense; and Servicios de Cirugía II, Medicina Preventiva y Oncología, Hospital Clínico San Carlos, Madrid, Spain.

Address reprint requests to Manuel Benito, PhD, Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense, Madrid, Spain 28040; email: benito{at}eucmax.sim.ucm.es

PURPOSE: Telomerase activity and p16 expression can be considered two of the most important molecular markers implicated in tumorigenesis. Our main aim was to study the cooperative role of both molecular alterations in the prognosis of patients surgically resected for non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: We have determined telomerase activity and p16 expression in a series of 98 prospectively collected NSCLC specimens obtained from patients who had undergone surgery without other treatment. Telomerase activity was investigated by a telomeric repeat amplification protocol enzyme-linked immunosorbent assay–based procedure, and p16 expression was examined by Western blot. Associations with survival were evaluated.

RESULTS: Positive results for telomerase activity were found in 82% of the cases, and this variable correlated with poor differentiation and recurrence of tumors. Lack of p16 expression was observed in 61% of tumors, and a significant association with tumor recurrence was also observed. By univariate analysis, both negative telomerase activity and p16-positive expression were significantly correlated with a better prognosis. Moreover, statistics for equality of survival distributions for telomerase, adjusted for p16, indicated a positive interaction between both parameters. For telomerase-positive tumors, p16 expression emerged as a significant independent protective variable, as indicated by Cox multivariate analysis (relative risk [RR], 0.214; P = .014). This protective effect was maintained only for stage I and II tumors (RR, 0.108; P = .046).

CONCLUSION: These results suggest that the combined telomerase activity and p16 expression analyses may be of prognostic importance in NSCLC, especially for patients affected by stage I and II tumors.

The first two authors contributed equally to this work.

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