An Immunohistochemical Study with Ultrastructural Correlations

To determine the specificity of immunostaining in the diagnosis of pulmonary neuroendocrine carcinomas, we studied 66 ultrastructurally characterized lung cancers with a panel of markers considered to be selective for neuroendocrine tumors (neuron-specific enolase, chromogranin A, Leu 7, synaptophysin) and B72.3, which is reported to be selective for non-small-cell carcinomas. Neuroendocrine tumors studied included 13 small-cell carcinomas, four low-grade neuroendocrine carcinomas, and two large-cell carcinomas with neuroendocrine differentiation. Non-neuroendocrine tumors included 26 adenocarcinomas, 10 squamous cell carcinomas, and 11 large-cell undifferentiated carcinomas. The following percentages of neuroendocrine carcinomas showing immunoreactivity for the various "neuroendocrine markers" were found: synaptophysin, 100%; neuron-specific enolase, 74%; chromogranin A, 37%; and Leu 7, 5%. However, carcinomas without morphologic features of neuroendocrine differentiation showed the following immunoreactivity: synaptophysin, 62%; neuron-specific enolase, 60%; chromogranin A, 17%; and Leu 7, 9%. B72.3 immunostaining was seen in 81% of the carcinomas without neuroendocrine features and in 31% of the small-cell carcinomas. We conclude that many of the commercially available antibodies used as neuroendocrine markers are nonspecific in the diagnosis of pulmonary neuroendocrine carcinomas.