TY - JOUR
T1 - High telomerase activity in primary lung cancers
T2 - Association with increased cell proliferation rates and advanced pathologic stage
AU - Albanell, Juan
AU - Lonardo, Fulvio
AU - Rusch, Valerie
AU - Engelhardt, Monika
AU - Langenfeld, John
AU - Han, Wei
AU - Klimstra, David
AU - Venkatraman, Ennapadam
AU - Moore, Malcolm A.S.
AU - Dmitrovsky, Ethan
PY - 1997/11/5
Y1 - 1997/11/5
N2 - Background: Telomerase enzyme activity is not detected in most normal cells, a phenomenon believed to be associated with limitations on cellular proliferation. Since this activity is detected in nearly all human tumors, including non-small-cell lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of the malignant phenotype. In this study, we determined whether telomerase activity was associated with tumor pathologic stage, tumor cell proliferation rates, and clinical outcome in a cohort of patients with resected non-small-cell lung cancer for whom long- term follow-up was available. Methods: Primary tumor specimens from 99 patients treated with surgery alone and six patients treated with surgery after chemotherapy were analyzed. Telomerase activity was measured by means of a modified Telomeric Repeat Amplification Protocol (TRAP) assay. Southern blot analysis of terminal restriction fragments was used to evaluate telomere length. Immunohistochemical analysis of Ki-67, a proliferation-associated nuclear antigen, was used to assess tumor cell proliferation. Results: Telomerase activity was detected in 84 of the 99 tumors treated with surgery alone; this activity was not detected in specimens of adjacent, benign lung tissue. Telomerase was detected in only three of six tumors resected after chemotherapy. For the surgery-alone group, statistically significant positive associations were found between the level of telomerase activity and tumor stage, lymph node metastasis, pathologic TNM (tumor-node-metastasis) stage, and Ki-67 immunostaining; a statistically significant inverse association was found between telomerase activity and patient age. No statistically significant differences in telomere length were found in relation to telomerase activity or pathologic stage. Telomerase activity was not found to be associated with clinical outcome in a multivariate Cox proportional hazards analysis adjusted for tumor stage and lymph node status. Conclusions: High telomerase activity is detected frequently in primary non-small-cell lung cancers that exhibit high tumor cell proliferation rates and advanced pathologic stage.
AB - Background: Telomerase enzyme activity is not detected in most normal cells, a phenomenon believed to be associated with limitations on cellular proliferation. Since this activity is detected in nearly all human tumors, including non-small-cell lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of the malignant phenotype. In this study, we determined whether telomerase activity was associated with tumor pathologic stage, tumor cell proliferation rates, and clinical outcome in a cohort of patients with resected non-small-cell lung cancer for whom long- term follow-up was available. Methods: Primary tumor specimens from 99 patients treated with surgery alone and six patients treated with surgery after chemotherapy were analyzed. Telomerase activity was measured by means of a modified Telomeric Repeat Amplification Protocol (TRAP) assay. Southern blot analysis of terminal restriction fragments was used to evaluate telomere length. Immunohistochemical analysis of Ki-67, a proliferation-associated nuclear antigen, was used to assess tumor cell proliferation. Results: Telomerase activity was detected in 84 of the 99 tumors treated with surgery alone; this activity was not detected in specimens of adjacent, benign lung tissue. Telomerase was detected in only three of six tumors resected after chemotherapy. For the surgery-alone group, statistically significant positive associations were found between the level of telomerase activity and tumor stage, lymph node metastasis, pathologic TNM (tumor-node-metastasis) stage, and Ki-67 immunostaining; a statistically significant inverse association was found between telomerase activity and patient age. No statistically significant differences in telomere length were found in relation to telomerase activity or pathologic stage. Telomerase activity was not found to be associated with clinical outcome in a multivariate Cox proportional hazards analysis adjusted for tumor stage and lymph node status. Conclusions: High telomerase activity is detected frequently in primary non-small-cell lung cancers that exhibit high tumor cell proliferation rates and advanced pathologic stage.
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U2 - 10.1093/jnci/89.21.1609
DO - 10.1093/jnci/89.21.1609
M3 - Article
C2 - 9362159
AN - SCOPUS:0030724731
SN - 0027-8874
VL - 89
SP - 1609
EP - 1615
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 21
ER -