COEXPRESSION OF NEURO-ENDOCRINE MARKERS AND EPITHELIAL CYTOSKELETAL PROTEINS IN BRONCHOPULMONARY NEURO-ENDOCRINE NEOPLASMS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 52  (1) , 39-51
Abstract
Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by EM, immunocytochemistry and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant number of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, .alpha.-MSH, vasoactive intestinal peptide, glucagon, insulin, substance P and neuron-specific enolase. EM revealed typical NE cell features, including filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the EM demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, appreciable amounts of cytokeratin polypepties 8, 18 and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas could be detected in the tumors tested. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. The findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.