Neuroendocrine differentiation in non-small cell lung cancer and its relation to prognosis and therapy

Aims: Histopathologists report the presence of neuroendocrine (NE) differentiation in non-small cell lung carcinoma (NSCLC) in up to a third of cases and are often questioned about its clinical relevance. The conclusions of previous studies have been inconsistent. This paper aims to provide an answer by examining a large series together with a comprehensive critique of the literature. Methods and results: Four hundred and thirty-nine cases of NSCLC were examined, immunohistochemically, using antibodies to chromogranin A (CGA), synaptophysin (SYN) and CD56/neural cell adhesion molecule (NCAM). Three hundred and forty-one cases had been treated with surgical resection and the remainder with chemotherapy. The results were compared with clinical outcome. Thity-six percent of cases had positive staining for at least one NE marker. CGA was positive in 5.5% of cases, SYN in 16.5% and NCAM in 28%. There was no association between the presence of NE markers and survival in either the surgically treated group or the chemotherapy-treated group. There was also no association between NE markers and response to chemotherapy in the latter group. Conclusions: The presence of immunohistochemically detected NE differentiation in NSCLC is not of prognostic significance.