Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer

Abstract

BACKGROUND/AIM: Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC) neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC). METHODS: A clinical trial included 158 patients (74% males and 26% females), with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion) or chemotherapy only in stage III (with pleural effusion) and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. RESULTS: A total of 53 patients (34%) had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively). Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.50/0), 34 (21.5%) and 33 (20.1%) patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (< 0.001); a two-year survival time noted in 30% of the patients (p = 0.000). One year follow-up survival time was longer in the patients with neuron specific enolase and chromogranin A expression lung cancer (p < 0.001). Synapthophysin expression was not statisticaly significant for survival (p > 0.05). CONCLUSION: The results of this study suggest that almost the third of the advanced NSCLC has neuroendocrine differentiation. The median survival time of the treated patients is longer when the tumor is associated with neuron specific enolase and chromogranin A expression.