Clinical significance of neuroendocrine phenotype in non-small-cell lung cancer

Non-small-cell lung carcinoma (NSCLC) describes a histologically heterogeneous group of tumours with variable clinical behaviour. Performance status, tumour stage and histological type have important prognostic implications, but clinical outcomes in individual patients remain unpredictable. A significant minority of NSCLCs (10%-30%) show neuroendocrine (NE) differentiation, and a number of studies have attempted to evaluate the therapeutic and prognostic significance of the expression of NE markers on the basis of the theoretical assumption that NE-differentiated tumours may be associated with an adverse prognosis and greater chemosensitivity. However, the results of these studies are conflicting: some have found that NE differentiation has a negative impact on survival, but others have failed to demonstrate any correlation with prognosis. Similar discrepancies have also been observed in terms of chemosensitivity. Nevertheless, these data are difficult to interpret because there is no gold standard defining NE differentiation, as is shown by the fact that the proportion of NE-differentiated NSCLCs varies according to the technique and marker used, although chromogranin A and synaptophysin show the best correlation with ultrastructural evidence of NE differentiation. In conclusion, there is no doubt that caution is required when interpreting the results of a number of studies questioning the clinical impact of the NE features of NSCLCs.