Electron microscopic and immunohistochemical analysis of neuroendocrine features in lung tumors

Introduction . Pulmonary tumors display several interesting aspects, especially the relationship between the cell biology of lung carcinoma and the response of these neoplasms to therapeutic intervention. The clinical significance of neuroendocrine differentiation in lung carcinomas remains unclear and is widely discussed. Material and methods. Immunohistochemical and electron microscopic evaluations were performed to assess the correlation between the immunohistochemical and ultrastructural evidence of neuroendocrine differentiation in pulmonary tumors with neuroendocrine features at the histological level. Forty eight surgically treated lung tumors were investigated. All tumors were classified histologically (depending on hematoxylin and eosin staining) as: carcinoid (5 ases), small cell lung carcinoma (2 cases), large cell neuroendocrine carcinoma (4 cases), squamous cell carcinoma (18 cases) and adenocarcinoma (16 cases). These tumors were immunostained with a panel of neuroendocrine markers (chromogranin A, synaptophysin, NSE) and cytokeratin. All of them were ultrastructurally investigated for the presence of neuroendocrine dense core granules. Results. The presence of neurosecretory granules was directly correlated with immunodetection of neuroendocrine markers: chromogranin A and synaptophysin. Immunoreactivity for NSE was not significant and this marker does not appear to be useful for detecting neuroendocrine features in pulmonary tumors. The results of this study indicate, however, that carcinomas without histologic features of neuroendocrine differentiation may show positive immunoreactivity to investigated markers. Our findings also demonstrate that 32% of adenocarcinomas were positive for chromogranin A and 62% – for synaptophysin; in squamous cell carcinomas 33% were positive for synaptophysin. We did not find any neuroendocrine features at ultrastructural level in this tumors. Summary . Positive immunoreactivity for selected neuroendocrine markers does not always correlate with light and electron microscopy characteristics of lung tumors.