title: Ultrastructure and chromogranin A immunogold labelling of ECL cell carcinoids.
abstract: Poorly differentiated neuroendocrine cells can be difficult to recognise. Sensitive methods are needed to label cells that have lost their ultrastructural features and have reduced concentrations of neuroendocrine markers. In gastric neoplasms, enterochromaffin-like cells might dedifferentiate and lose their characteristic granules and secretory vesicles, making detection of such cells increasingly difficult. However, chromogranin A (CgA) immunogold labelling could provide sensitive and specific detection of gastric neuroendocrine cells. We present ultrastructural findings, CgA immunogold labelling as well as conventional immunohistochemical findings of two human enterochromaffin-like cell carcinoids. Electron-dense granules of poorly differentiated cells were less intensely labelled than granules in well-differentiated cells. Granules with atypical shape as well as punctuate granules previously found in neuroendocrine neoplasms were also CgA labelled. The CgA labelling efficacy after antigen retrieval in an alkaline solution was higher after heating in an autoclave at 135 degrees C compared to a microwave at 100 degrees C for both granules and secretory vesicles without significant deterioration of the ultrastructure. In conclusion, the use of CgA immunogold labelling could ensure a specific classification of cells with neuroendocrine granules and be a supplement to immunohistochemical examination of poorly differentiated tumours.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. reidar.fossmark@medisin.ntnu.no
authors.forename: Reidar
authors.initials: R
authors.lastname: Fossmark
authors.forename: Tom C
authors.initials: TC
authors.lastname: Martinsen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Qvigstad
authors.forename: Marianne Ø
authors.initials: MØ
authors.lastname: Bendheim
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kopstad
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashima
authors.forename: Helge L
authors.initials: HL
authors.lastname: Waldum
mesh_terms: D000368:Aged; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000556:secondary / Q000648:ultrastructure*; D002454:Cell Differentiation; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism*; D019861:Enterochromaffin-like Cells / Q000378:metabolism* / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D022142:Secretory Vesicles / Q000378:metabolism / Q000648:ultrastructure; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary / Q000648:ultrastructure; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000648:ultrastructure*
chemical_list: C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins