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Extraepithelial origin of gastrointestinal carcinoids
S151
EXTRAEPITHELIAL ORIGIN OF GASTROINTESTINAL CARCINOIDS H.H~fler, L . A ~ k , M.Ratzenhofer und Ph.U.Heitz (Institute of Pathology,Univ. Graz/Austria, Institute of Pathology, Univ.Basle/Switzerland) Extraepithelial endocrine cells (strc~al e.c.) localized within nerve fibers and covered by a ccalmon basal lamina proliferate in certain forms of neurogenic appendicopathy - a nonpurulent appendicitis variant. We used this very con~on "model disease" to study hyperplasia of stromal e.c. and the early development of appendix carcinoid, applying the usual silver methods, ~ o cytochemistry (PAP technique for 5-HT, SOM, SP, VIP, GLI, PP, GAST/CCK, NT, secretory conloonent-SC and neuron-specific enolase-NSE) and electron microscopy. In both the normal appendix and neurogenic appendicopathy, the stromal e.c. are mainly argentaffine and argyrophilic and are ~ o r e a c t i v e to 5-HT, slightly so to SP and rarely to SOM. The ~ o c y t o c h e m i c a l demonstration of NSE is particularly significant, as it shows the ganglion cells and axons, as well as the endocrine cells in epithelium and stroma, regardless of peptide content. Light and electron microscopy showed the development of carcinoids from individual stromal e.c. to small clusters of proliferated cells and then to small solid or glandular microcarcinoids and larger tumors. Microcarcinoids were observed in the appendix which could not be silvered, and did not show an inlmmnocytochemical reaction to the above-mentioned peptide hormones. The majority of tumor cells in classical, non-mucus-producing (micro-) carcinoids is, however, always NSE reactive. NSE reactivity is also retained in larger carcinoids. Nerve fibers in direct contact with endocrine cells were seen in all stages of carcinoid development in the appendix, as well as in two cases of gastric microcarcinoidosis and other intestinalcarcinoids. In one goblet-cell carcinoid of the appendix the NSE-reaction remained negative, while, in contrast to classical earcinoids, most of the tumor cells were SC-reactive, indicating that goblet-cell carcinoids form a special type of tumor. We therefore suggest the gastrointestinal carcinoids to be derived from often multiple - endocrine cell groups localized in the mucosal stroma, distant from the epithelium.
A DOUBLE IMMUNOGOLD STAINING METHOD FOR THE SIMULTANEOUS ULTRASTRUCTURAL LOCALISATION OF REGULATORY PEPTIDES. F.J. Tapia, I.M. Varndell, L. Probert, E.J. Gosselin, J. De Mey & J.M. Polak. Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, United Kingdom. Immunocytochemical techniques at the electron microscope level have shown regulatory peptides to be stored in electron-dense secretory granules of endocrine cells and nerves. Recent studies have suggested that the coexistence of molecular forms of peptides with amines or with other peptides may determine the morphological pattern of the secretory granules. One particular technique, the immunogold staining method, which is based on the conjugation of colloidal gold particles to immunoglobulins, has been instrumental in demonstrating a wide range of tissue-bound antigens at both light and electron microscope levels. In this study we have applied a modification of the immunogold staining method for the simultaneous detection of two separate antigens in a single tissue section, using a variety of region-specific antisera to different peptides. Peptide antisera were raised in rabbits or in guinea pigs and these were applied sequentially or simultaneously to grid-mounted tissue sections. Antigenic sites were visualised at the EM level using antisera raised in goats, conjugated with
EXTRAEPITHELIAL ORIGIN OF GASTROINTESTINAL CARCINOIDS H.H~fler, L . A ~ k , M.Ratzenhofer und Ph.U.Heitz (Institute of Pathology,Univ. Graz/Austria, Institute of Pathology, Univ.Basle/Switzerland) Extraepithelial endocrine cells (strc~al e.c.) localized within nerve fibers and covered by a ccalmon basal lamina proliferate in certain forms of neurogenic appendicopathy - a nonpurulent appendicitis variant. We used this very con~on "model disease" to study hyperplasia of stromal e.c. and the early development of appendix carcinoid, applying the usual silver methods, ~ o cytochemistry (PAP technique for 5-HT, SOM, SP, VIP, GLI, PP, GAST/CCK, NT, secretory conloonent-SC and neuron-specific enolase-NSE) and electron microscopy. In both the normal appendix and neurogenic appendicopathy, the stromal e.c. are mainly argentaffine and argyrophilic and are ~ o r e a c t i v e to 5-HT, slightly so to SP and rarely to SOM. The ~ o c y t o c h e m i c a l demonstration of NSE is particularly significant, as it shows the ganglion cells and axons, as well as the endocrine cells in epithelium and stroma, regardless of peptide content. Light and electron microscopy showed the development of carcinoids from individual stromal e.c. to small clusters of proliferated cells and then to small solid or glandular microcarcinoids and larger tumors. Microcarcinoids were observed in the appendix which could not be silvered, and did not show an inlmmnocytochemical reaction to the above-mentioned peptide hormones. The majority of tumor cells in classical, non-mucus-producing (micro-) carcinoids is, however, always NSE reactive. NSE reactivity is also retained in larger carcinoids. Nerve fibers in direct contact with endocrine cells were seen in all stages of carcinoid development in the appendix, as well as in two cases of gastric microcarcinoidosis and other intestinalcarcinoids. In one goblet-cell carcinoid of the appendix the NSE-reaction remained negative, while, in contrast to classical earcinoids, most of the tumor cells were SC-reactive, indicating that goblet-cell carcinoids form a special type of tumor. We therefore suggest the gastrointestinal carcinoids to be derived from often multiple - endocrine cell groups localized in the mucosal stroma, distant from the epithelium.
A DOUBLE IMMUNOGOLD STAINING METHOD FOR THE SIMULTANEOUS ULTRASTRUCTURAL LOCALISATION OF REGULATORY PEPTIDES. F.J. Tapia, I.M. Varndell, L. Probert, E.J. Gosselin, J. De Mey & J.M. Polak. Department of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 OHS, United Kingdom. Immunocytochemical techniques at the electron microscope level have shown regulatory peptides to be stored in electron-dense secretory granules of endocrine cells and nerves. Recent studies have suggested that the coexistence of molecular forms of peptides with amines or with other peptides may determine the morphological pattern of the secretory granules. One particular technique, the immunogold staining method, which is based on the conjugation of colloidal gold particles to immunoglobulins, has been instrumental in demonstrating a wide range of tissue-bound antigens at both light and electron microscope levels. In this study we have applied a modification of the immunogold staining method for the simultaneous detection of two separate antigens in a single tissue section, using a variety of region-specific antisera to different peptides. Peptide antisera were raised in rabbits or in guinea pigs and these were applied sequentially or simultaneously to grid-mounted tissue sections. Antigenic sites were visualised at the EM level using antisera raised in goats, conjugated with