Balance between cell division and cell death as predictor of survival in patients with non-small-cell lung cancer

OBJECTIVE: To evaluate the prognostic value of the balance between apoptosis and proliferation in non-small-cell lung cancer (NSCLC). METHODS: Paraffin-embedded sections from a consecutive series of radically resected NSCLCs were scored for apoptosis (in situ DNA nick end labeling assay) and proliferation (immunohistochemistry for MIB-1). A total of 1,000 cells were counted per case, to obtain apoptotic (AI) and MIB-1 indices. Other potential prognostic indicators (pT, pN, pStage and histology) and p53 status were also evaluated. RESULTS: Univariate analysis showed that adenocarcinomatous histotype (p = 0.03), nodal involvement (p = 0.04), higher pStage (p = 0.001) and the combination of low AI and high MIB-1 expression (p = 0.03) were associated with poorer outcome. The significant prognostic value of the combination 'low AI/high MIB-1' was also confirmed in a multivariate analysis after adjustment for other covariates. CONCLUSION: These results underline the importance of considering apoptosis and proliferation together to identify a subgroup of NSCLC associated with poor survival.