The value of neuroendocrine markers for response to therapy and survival in patients with advanced non-small cell lung cancer

Abstract

Introduction. Non-small cell lung cancer (NSCLC) accounts for about 70-80% of all lung cancers. In comparison with small cell lung cancer, NSCLC has relatively low therapy response. Discovery of neuroendocrine markers within the NSCLC group (10-30%) has initiated the issue of their importance in the therapy and prognosis. Objective. The aim of this study was to determine the influence of neuroendocrine differentiation on treatment response and survival in patients with advanced NSCLC. Methods. A clinical trial included 236 patients (73.7% males), with diagnosis of NSCLC, determined by histological verification. These patients were treated by combined chemo- and X-ray therapy at stage III (without pleural effusion) or chemotherapy only at stage III (with pleural effusion) and stage IV of NSCLC. When the progression had been noted at the stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron-specific enolase (NSE), chromogranin A (ChrA) as well as synapthophysin (SYN) expression in tissue examples was determined by immunohistochemical analysis with monoclonal mouse anti human bodies (DAKO Comp, Denmark). The treatment was conducted during 4 to 6 chemotherapeutic cycles. The efficacy was assessed after the therapy regimen; median survival time was assessed after the randomization. Results. NSE, ChrA and SYN expression were noted in 56 (23.7%), 33 (13.9%) and 39 (16.5%) patients, respectively. Better therapeutic response was significantly higher in patients with expression of NSE, ChrA and SYN (p<0.05). There was significant correlation between therapy response and the percentage of positive tumour cells with neuroendocrine differentiation (p<0.05). The one-year and two-year follow-up survival period in patients with neuroendocrine expression was 64% (without expression 28%; p<0.001) and 30% (p=0.000). Conclusion. Tissue expression of neuroendocrine markers influences greatly a therapeutic response in patients with advanced stage of NSCLC. Better therapeutic response was recorded in patients with positive expression of neuroendocrine markers and higher percentage of positive tumour cells. Median survival time is higher in patients in III or IV stage of NSCLC, when neuroendocrine markers are expressed.