Immunostaining in the diagnosis of pulmonary neuroendocrine carcinomas. 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.