R. Buffa

Endocrine cells of the gastric mucosa

Publisher Summary This chapter discusses the endocrine cells of the gastric mucosa. On ultrastructural and histochemical grounds, non-enterochromaffin (EC) endocrine cells of the gastrointestinal mucosa were classified as four or six independent cell types. Six distinct types of endocrine cells were added to the well-known EC cells. Staining patterns in light and electron microscopy amine histochemistry, and/or immunohistochemistry confirm the existence of this manifold population of endocrine cells. So far, biochemical and functional studies support the existence of four endocrine products, namely, 5-hydroxytryptamine (5HT), gastrin, histamine, and gastro glucagon. Thus, based on morphological evidence, more hormones than those presently reported are to be expected from the gastric mucosa. The interaction between endocrine cells and stimuli coming from the lumen or from blood and the nervous system; both the hypothesis of a direct interaction of luminal stimuli with the endocrine cell and a more complex mechanism involves specialized receptors and local or long central reflexes must be considered. The close dependence of most digestive functions on gastrointestinal hormones, the behavior of gastrointestinal endocrine cells in some digestive diseases associated with severe functional derangements such as peptic ulcer, malabsorption, pancreatitis, and the sequelae of surgical procedures affecting the alimentary canal—should be extensively investigated.

Immunohistochemical Identification of the Cholecystokinin Cell in the Intestinal Mucosa

In indirect immunofluorescence tests, antibodies against pure porcine cholecystokinin (CCK) have detected specific CCK cells in the duodenal and jejunal mucosa of the dog and man. The CCK cells were scattered in the epithelium of the crypts, although some were in the villi. No CCK cells were found in the stomach, pancreas, terminal ileum, or colon. Some pyloric G cells also showed some reactivity with CCK antiserum, but absorption of CCK antiserum with gastrin C terminal pentapeptide prevented the staining of pyloric cells and provided specific staining of intestinal CCK cells. Anti-human gastrin I serum stained some intestinal cells too. Most of such cells did not react when gastrin antiserum was absorbed with pure CCK (a treatment that did not prevent the staining of pyloric gastrin cells); they were interpreted as cross-reacting CCK cells rather than as intestinal gastrin cells.

Types of endocrine cells in the human colon and rectum.

SummaryAt least four types of endocrine-like cells have been detected histochemically in the mucosa of the human colon and rectum, i.e. argentaffin cells storing 5-hydroxytryptamine (5 HT) and non-argentaffin cells reacting with glucagon, somatostatin and bovine pancreatic peptide (BPP) antibodies. Ultrastructurally, four main types and three rare types of endocrine-like cells have been identified. Among the former cells were: (1) argentaffin EC1 cells, known to store 5 HT and substance P, (2) poorly argyrophil L cells, corresponding to the glucagon-immunoreactive cells storing enteroglucagon or glucagon-like immunoreactivity (GL1), (3) inconstantly argyrophil F-like cells, possibly corresponding to BPP-immunoreactive cells, and (4) fairly argyrophil H cells of unknown function. Rare D cells, corresponding to somatostatin cells, N cells, corresponding to neurotensin cells, and P cells, of unknown function, have been also found.

Identification of the intestinal cell storing gastric inhibitory peptide

SummarySmall intestinal mucosal samples from man, pig and dog, were subjected to sequential or correlative silver impregnation techniques, applied to immunocytochemical preparations and at the ultrastructural level.The cell reacting with anti-GIP sera was identified as the ultrastructurally classified K cell and we propose that the term GIP cell be used in place of the latter.This cell can thus be recognized by its strong reactivity with the Sevier-Munger staining procedure, provided that the equally strongly reacting EC cell is excluded by virtue of its argentaffinity with the Masson technique.

Synaptophysin immunoreactivity and small clear vesicles in neuroendocrine cells and related tumours

Synaptophysin (protein p38) immunoreactivity has been detected immunohistochemically in neuroendocrine cells of the human adrenal medulla, carotid body, skin, pituitary, thyroid, lung, pancreas and gastrointestinal mucosa as well as in 87 out of 93 neuroendocrine tumours investigated, including pheochromocytomas, chromaffin and non-chromaffin paragangliomas, ganglioneuromas, pituitary adenomas, thyroid medullary carcinomas, parathyroid adenomas, lung carcinoids and neuroendocrine carcinomas, pancreatic and gut endocrine tumours and cutaneous merkelomas. Parallel ultrastructural investigation of synaptophysin-reactive cells and tumours revealed the presence, in addition to dense-cored, secretory granules, of a population of pleomorphic, small, clear vesicles resembling synaptic vesicles of nerve terminals as well as the synaptophysin immunoreactive vesicles already described in rat adrenal medullary and pituitary cells. Synaptophysin immunoreactivity showed several differences in its distribution among tumour and non-tumour endocrine cells when compared to chromogranin A immunoreactivity, a well known marker of the core of endocrine granules. Synaptophysin represents a reliable general marker of neuroendocrine cells and tumours, which may be useful in diagnostic histopathology.

Multiple endocrine cell types in thyroid medullary carcinoma. Evidence for calcitonin, somatostatin, ACTH, 5HT and small granule cells.

10 cases of thyroid medullary carcinoma (TMC) have been studied ultrastructurally and histochemically. Well differentiated calcitonin-producing C cells were present in all tumours, being prevalent in 9 cases. 5-Hydroxytryptamine (5HT) storing cells were found in two cases, somatostatin immunoreactive cells in at least 5 cases and ACTH-immunoreactive cells in 4 cases. Ultrastructurally, at least 3 types of apparently non-C cells were observed. Type 1 cells with large, poorly osmiophilic granules resembling those of gastroenteropancreatic D cells, were present in 6 cases; they appeared to correlate well with somatostatin immunoreactive cells. Type 2 cells with large osmiophilic granules were found in 5 cases; they resembled ACTH-MSH cells of the human pituitary and may correspond to the ACTH-immunoreactive cells of light microscopy. Type 3 cells with small granules and an unknown function were found in 6 cases, always in scarce number. It is concluded that TMC, although mainly made up of C cells, usually contains large proportions of other endocrine cell types.

On the Immunocytochemical Localization of the Vasoactive Intestinal Polypeptide

The distribution of vasoactive intestinal polypeptide (VIP) immunoreactive nerves and endocrine cells in the gastrointestinal tract and pancreas of a number of mammalian and submammalian species has been examined in order to throw light on the exact localization of this peptide. Seven out of 8 VIP antisera demonstrated numerous nerve fibers in the gut, whereas one antiserum (TR2) revealed only scattered, few nerve fibers. The distribution of endocrine cells demonstrated by the different VIP antisera varied considerably. Thus, some antisera demonstrated only endocrine cells in the feline antrum, others only colonic endocrine cells and still others only endocrine cells of the upper gut and pancreas. The variability in staining pattern of endocrine cells as well as recent radioimmunological data makes it opportune to suggest that true VIP is a neuronal peptide and that endocrine cells store peptides resembling, but not being identical with, VIP (VIPoids).

Clinical relevance of cyclin D1 protein overexpression in laryngeal squamous cell carcinoma.

PURPOSE To investigate the prognostic relevance of cyclin D1 gene overexpression in laryngeal squamous cell carcinomas (LSCCs). PATIENTS AND METHODS The overexpression of cyclin D1 was analyzed in 149 LSCC patients with a median follow-up duration of 60 months using the DCS6 monoclonal antibody; only cases that overexpressed cyclin D1 in more than 5% of neoplastic cells were considered positive. RESULTS Forty-eight cases (32.2%) were immunoreactive to the DCS6 antibody. Cyclin D1 overexpression was significantly associated with tobacco smoking and alcohol consumption, tumor extension, advanced clinical stage, and the presence of lymph node metastases. Univariate analysis showed that a shorter disease-free and overall survival were significantly associated with supraglottic site, tumor extension, advanced clinical stage, and cyclin D1 overexpression. At multivariate analysis, tumor extension and cyclin D1 overexpression were significantly associated with tumor recurrence, whereas tumor extension, supraglottic site and, at a borderline level of statistical significance, cyclin D1 overexpression, were associated with reduced overall survival. CONCLUSION The overexpression of cyclin D1 in LSCC is associated with unfavorable clinicopathologic features and represents an independent significant predictor of laryngeal carcinoma prognosis, particularly for disease-free survival. This indicates that cyclin D1 evaluation may be a further useful element for selecting subgroups of patients who should be treated with more aggressive therapies.

The endocrine component of prostatic carcinomas, mixed adenocarcinoma-carcinoid tumours and non-tumour prostate. Histochemical and ultrastructural identification of the endocrine cells.

Two types of endocrine‐paracrine (EP) cells have been detected histochemically and ultrastructurally in normal and hyperplastic prostates; i.e. type 1 cells resembling intestinal EC (enterochromaffin) cells and type 2 cells similar to urethral EP cells previously reported by Casanova et al. (1974). About one‐third of the 40 prostatic carcinomas studied contained EP cells. Four tumours showed a very large number of EP cells: two of these were composite tumours exhibiting both adenocarcinomatous and carcinoid patterns. These four tumours have also been studied histochemically and ultrastructurally. ACTH and β‐endorphin immuno‐reactive cells, ultrastructurally resembling pituitary corticotrophic cells, have been identified in three tumours. Cells identical with type 1 and type 2 cells of the normal prostate were detected in two cases and in a further case, respectively.

Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer.

PURPOSE To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had </= 10% of p21 and </= 50% of p27 immunoreactive neoplastic cells. RESULTS In 41 cases (31.1%), p21 was expressed in </= 10% of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 10% of neoplastic cells. In 11 cases (8.3%), p27 was expressed in less than 5% of neoplastic cells; in 39 cases (29.6%), it was expressed in 5% to 50% of neoplastic cells; and in 82 cases (62.1%), it was expressed in more than 50% of the neoplastic cells. Low levels of p21 expression were associated with poor histologic differentiation and lymph node metastases. Low levels of p27 expression were associated with tumor extension and advanced clinical stage. Expression of p21 and p27 was not correlated with p53 gene status, and low p27 expression was more frequently detected in the cyclin D1-positive cases, with a borderline level of statistical significance. At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates. At multivariate analysis, high cyclin D1 expression and low p27 expression were the only significant covariates. The patients with a cyclin D1(+)/p27(-) phenotype had the poorest disease-free and overall survival rates. CONCLUSION Our study provides evidence that the immunohistochemical evaluation of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma.