HIGH TELOMERASE ACTIVITY IN PRIMARY LUNG CANCERS - ASSOCIATION WITH INCREASED CELL-PROLIFERATION RATES AND ADVANCED PATHOLOGICAL STAGE

Background: Telomerase enzyme activity is not detected in most normal cells, a phenomenon believed to be associated with limitations on cell ular proliferation, Since this activity is detected in nearly all huma n tumors, including non-small-cell lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of the malig nant phenotype, In this study, we determined whether telomerase activi ty was associated with tumor pathologic stage, tumor cell proliferatio n rates, and clinical outcome in a cohort of patients with resected no n-small-cell lung cancer for whom long-term follow-up was available, M ethods: Primary tumor specimens from 99 patients treated with surgery alone and six patients treated with surgery after chemotherapy were an alyzed, Telomerase activity was measured by means of a modified Telome ric Repeat Amplification Protocol (TRAP) assay, Southern blot analysis of terminal restriction fragments was used to evaluate telomere lengt h, Immunohistochemical analysis of Ki-67, a proliferation-associated n uclear antigen, was used to assess tumor cell proliferation, Results: Telomerase activity was detected in 84 of the 99 tumors treated with s urgery alone; this activity was not detected in specimens of adjacent, benign lung tissue, Telomerase was detected in only three of six tumo rs resected after chemotherapy, For the surgery-alone group, statistic ally 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 statis tically significant inverse association was found between telomerase a ctivity and patient age, No statistically significant differences in t elomere length were found in relation to telomerase activity or pathol ogic stage, Telomerase activity was not found to be associated with cl inical outcome in a multivariate Cox proportional hazards analysis adj usted for tumor stage and lymph node status, Conclusions: High telomer ase activity is detected frequently in primary non-small-cell lung can cers that exhibit high tumor cell proliferation rates and advanced pat hologic stage.