Neuroendocrine (NE)
neoplasms of the human bronchopulmonary tract were examined by electron microscopy, 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 numbers of cells that immunostained for one or more of the following neuroendocrine markers tested:
bombesin,
calcitonin,
ACTH,
leu-enkephalin,
gastrin,
serotonin,
somatostatin,
alpha-melanocyte-stimulating hormone,
vasoactive intestinal peptide,
glucagon,
insulin,
substance P, and
neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules.
Tumor cells contained 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 electron microscopic 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, we could detect, in the
tumors tested, appreciable amounts of
cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung
carcinomas such as
adenocarcinomas.
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. These 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.