Relevance of proliferative and pro-apoptotic factors in non-small-cell lung cancer for patient survival

This investigation first set out to analyse which cellular proliferative an d apoptotic factors, in addition to the clinical prognostic factors, are mo st predictive in patients with non-small-cell lung carcinomas (NSCLC). To t his purpose, we related the proliferative factors proliferating cell nuclea r antigen (PCNA), cyclin A, cyclin D1, cyclin-dependent kinase 2 (cdk2), cd k4 and the proportion of cell cycle phases in NSCLC to the survival times o f 150 patients. Additionally, we associated the expressions of Fas, Fas lig and and caspase-3 in NSCLC to patient survival. Immunohistochemistry was us ed to determine the proteins and flow cytometry to assess the proportion of cell cycle phases. Patients with PCNA-positive carcinomas had significantl y shorter survival times than patients with PCNA-negative carcinomas (media n survival times: 51 vs 89 weeks). Corresponding results were obtained with the factor cyclin A (64 vs 92 weeks), with the factor cdk2 (76 vs 89 weeks ), with the factor cdk4 (62 vs 102 weeks) and with the proportion of S phas es (86 vs 121 weeks). Patients with an expression of the apoptotic factors had a more favourable prognosis than patients with negative carcinomas. The median survival times of cancer patients with Fas expression was 86 weeks and of those without Fas expression only 69 weeks. Corresponding results we re obtained with the Pas ligand (87 vs 41 weeks) and caspase 3 (87 vs 34 we eks), in order to determine whether a combination of factors can yield impr oved prognostic information, we investigated all possible combinations of t he proliferative and apoptotic factors. Patients with tumours having a high proliferative activity, but which did not express apoptotic factors had th e shortest survival times while patients with a low proliferative activity and a high expression of apoptotic factors had the most favourable outcome. A multivariate analysis (Cox model) of the cellular and clinical prognosti c factors indicated that stage, lymph node involvement, Fas, PCNA and cycli n A are the most important prognostic factors for the clinical outcome of p atients with non-small-cell lung carcinomas. (C) 2000 Cancer Research Campa ign.