R. Fiocca

Cathepsin E in follicle associated epithelium of intestine and tonsils: localization to M cells and possible role in antigen processing

A specific rabbit anti-human serum was used selectively to localize the aspartic proteinase cathepsin E to follicle associated epithelium (FAE) of human and rat intestine, including jejunum, ileum, appendix, colon and rectum, as well as of human palatine, pharyngeal and lingual tonsils. Coexpression of class II histocompatibility antigen HLA-DR antigen has been observed in some of the cathepsin E-positive epithelial cells. In addition, cathepsin E has been detected in a few mononuclear cells of intestinal lymphoid structures and tonsils resembling interdigitating reticulum cells of lymph nodes. Another aspartic proteinase, cathepsin D, has been found to be poorly represented in FAE and intensely expressed by macrophages. Electron immunocytochemistry localized cathepsin E to endosomal vesicles and endoplasmic reticulum of M cells in rat and human ileum as well as of M-like cells in human palatine tonsil. The results suggest a possible role of endosomal cathepsin E in the processing of macromolecules and microorganisms transported by M cells and related epithelial cells to mucosal associated lymphoid tissue (MALT).

Epithelial Cytotoxicity, Immune Responses, and Inflammatory Components of Helicobacter pylori Gastritis

To clarify the mechanisms of the gastric mucosal immune--inflammatory response to Helicobacter pylori infection, surgical and biopsy specimens from asymptomatic uninfected, gastritis-free individuals and from H. pylori-positive ulcer patients with chronic gastritis were investigated using light and electron microscopy. Activation of the antigen-transporting endocytic--endosomal system, enhanced expression of the antigen-processing enzyme cathepsin E and de novo expression of antigen-presenting human leukocyte antigen (HLA)-DR molecules have been detected in H. pylori-colonized gastric epithelium. These findings may be crucial in the production of a mucosal immune-inflammatory response to H. pylori infection. Cytoplasmic swelling and vacuolation, micropapillary change, mucin loss, erosion of the juxtaluminal cytoplasm and cell desquamation were the main effects of bacterial cytotoxicity on gastric surface-foveolar epithelium. Activated macrophages and granulocytes (partly linked to the mucosal IgG immune response) concentrate in the foveolar-neck region of the mucosa, where they may enhance damage and impair regeneration of the epithelium. Both direct bacterial cytotoxicity and inflammatory cell aggression against gastric epithelium may predispose the patient to peptic ulcer disease.

Session 5: Morphology and Pathogenesis of Endocrine Hyperplasias, Precarcinoid Lesions, and Carcinoids Arising in Chronic Atrophic Gastritis

Solcia E, Fiocca R, Villani L, Gianatti A, Cornaggia M, Chiaravalli A, Curzio M, Capella C. Morphology and pathogenesis of endocrine hyperplasias, precarcinoid lesions, and carcinoids arising in chronic atrophic gastritis. Scand J Gastroenterol 1991, 26(suppl 180), 146–159The spectrum of endocrine cell changes occurring in 80 cases of body-fundus chronic atrophic gastritis (CAG), mostly type A or multifocal, including various types of hyperplasia, precarcinoid lesions (20 cases), and neoplasia (carcinoid, 24 cases) have been analyzed histologically, histochemically, and ultrastructurally. Changes associated with gland atrophy, pyloric- or intestinal-type metaplasia, regenerative hyperplasia, and hypergastrinemia have been identified and their neoplastic potential evaluated in the light of their proliferative capacity (bromodeoxyuridine incorporation) and clinicopathologic behavior. A close link between disseminated precarcinoid lesions of non-tumor mucosa and multiple carcinoids (carcinoidosis) arising in...

Helicobacter colonization and histopathological profile of chronic gastritis in patients with or without dyspepsia, mucosal erosion and peptic ulcer: A morphological approach to the study of ulcerogenesis in man

Helicobacter pylori colonization and the incidence, severity, activity and topography of gastritis were investigated systematically in antrum and corpus mucosal biopsies of 1177 subjects undergoing endoscopy in the absence of gastric complaints (asymptomatic, 49) or for non-ulcer dyspepsia (NUD; 631 patients, 72 of whom had gastric and/or duodenal erosions), active gastric ulcer (GU, 76 patients), active duodenal ulcer (DU, 138 patients), and healed gastric (HGU, 39 cases) or duodenal ulcer (HDU, 230 cases). In the antrum,H. pylori colonization and the incidence, severity and activity of gastritis increased progressively in the sequence asymptomatic, erosion-free NUD, erosive NUD, healed ulcer and active ulcer. The same trend was observed in the corpus as regardsH. pylori and gastritis incidence, whereas the severity and activity of gastritis were lower in active DU and erosive NUD and higher in active, proximal GU than in the remaining patients. Active DU and erosive NUD showed the highest incidence of nonatrophic gastritis and lowest type-A or AB atrophic gastritis, while active GU had lowest normal mucosa or type-A gastritis and highest type-B atrophic gastritis. In conclusion,H. pylori colonization and gastritis incidence, severity and, especially, activity of the antrum might all contribute to mucosal erosion and ulceration, whereas the same factors, at least in part and with the exception of proximal GU, seem to have a preventive role when affecting corpus mucosa.

Characterization of Four Main Cell Types in Gastric Cancer: Foveolar, Mucopeptic, intestinal Columnar And Goblet Cells: An histopathologic, histochemical and ultrastructural study of “early” and “advanced” tumours

Gastrectomy specimens of 148 gastric cancers, 40 of them being intramucosal or microinvasive, 27 penetrating the submucosa and 81 invading the muscularis propria, with or without involvement of the serosa and perigastric tissues, have been investigated with conventional histopathologic techniques, mucin histochemistry and electron microscopy to characterize the various lines of tumour cell differentiation and to correlate these with the histologic patterns of tumour growth. More or less differentiated intestinal columnar, intestinal goblet, gastric foveolar or mucopeptic cells were recognized in most tumours, of glandular, diffuse or mucoid type. Although simultaneous expression of more than one cell type into the same tumour occurred very frequently, intestinal columnar cells were more prominent in tubular adenocarcinomas, goblet cells (especially of colorectal type) in mucoid cancers, mucopeptic cells in diffuse cancers of invasive desmoplastic type and foveolar cells in diffuse cancers of intramucosal signet-ring cell type. In general, an increased tendency to foveolar cell differentiation and a reduced tendency to mucopeptic differentiation has been found in intramucosal cancers as compared to invasive cancers. It is concluded that the type of tumour cell differentiation, which might have some influence on the natural history of gastric cancer, is better related with more defined tumour subtypes than with the usually recognized glandular or diffuse patterns.

Helicobacter pylori vacuolating toxin accumulates within the endosomal-vacuolar compartment of cultured gastric cells and potentiates the vacuolating activity of ammonia.

This study explored the relationship between vacuolating toxin and ammonia in the genesis of Helicobacter pylori‐induced vacuolation in cultured human gastric cells and investigated the intracellular sites of toxin accumulation. Neutral red dye uptake and electron microscopy were used in the investigation of the respective roles of, and of the reciprocal interaction between, toxin and ammonia in cell vacuolation and ultrastructural immunocytochemistry was used for the identification of the intracellular sites of internalized toxin. Toxin was found to cause an expansion of the endosomal compartment, where it accumulates after cellular internalization. However, toxin does not form large, neutral red‐positive vacuoles unless combined with ammonia, whose moderate vacuolating activity is markedly potentiated by the toxin. It is concluded that the toxin accumulated within the endosomal compartment alters the morphology and function of this organelle and plays a permissive role towards cell vacuolation, possibly by increasing the accumulation of protonated ammonia within endosomes. In turn, ammonia induces excessive dilatation of the endosomes with reciprocal fusion of their membranes, thus causing cytoplasmic vacuolation.

Distinct profiles of gastritis in dyspepsia subgroups: Their different clinical responses to gastritis healing after helicobacter pylori eradication

BACKGROUNDnA contribution of Helicobacter pylori gastritis to the pathogenesis of non-ulcer dyspepsia (NUD) remains uncertain.nnnMETHODSnAdministration of an appropriate clinical questionnaire followed by endoscopy allowed us to select, among 139 outpatients with dyspepsia, 87 non-ulcer dyspepsia patients with more severe and group-distinctive symptoms, 35 of whom were classified as having ulcer-like (ULD). 38 as dysmotility-like (DLD), and 14 as reflux-like dyspepsia (RLD). Biopsy specimens were evaluated for H. pylori gastritis in accordance with the Sydney system. The 70 H. pylori-positive cases were treated with omeprazole, 20 mg twice daily, and amoxycillin, 1 g three times daily for 2 weeks.nnnRESULTSnHigher rates of H. pylori colonization were found histologically in the gastric mucosa of ULD (91%) and RLD (86%) than in that of DLD (68%) or asymptomatic (42%) patients. ULD differed from RLD patients in their higher score of antritis activity. Three and 6 months after H. pylori eradication ULD (but not DLD) showed significant regression of dypspetic symptoms scores.nnnCONCLUSIONSnIt seems likely that H. pylori gastritis, with special reference to active antritis, is among causative factors of ULD. Its role in the pathogenesis of RLD and DLD needs further investigation.

Gastric Endocrine Cells and Gastritis in Patients Receiving Long-Term Omeprazole Treatment

Both argyrophil endocrine cells and gastritis were investigated in 2,120 biopsies of gastric corpus mucosa from 443 out of 448 patients receiving long-term (for periods ranging from several months to 4 years) omeprazole treatment. None of the patients showed neoplasia or dysplasia, either endocrine or non-endocrine. In 123 out of 443 patients (27.8%), endocrine hyperplasia of diffuse (9.3%), linear (4.1%) or micronodular (14.4%) type was detected either before or at some time during treatment. Chronic atrophic gastritis was found in 45 (10.2%) patients, 60% of whom also showed micronodular hyperplasia. In patients with chronic atrophic gastritis, micronodular hyperplasia occurred in 49% of 96 biopsies, compared with 6% of 1,083 biopsies from patients with non-atrophic chronic gastritis and 2% of 941 biopsies from patients with no evidence of gastritis. In 202 patients treated with omeprazole for at least 330 days, the incidence of micronodular hyperplasia increased from 2.5% at the first biopsy to 10.4% at the final biopsy, while the incidence of chronic atrophic gastritis increased from 1.0% to 13.0%. The present and parallel studies suggest that progression of gastritis is inherent in the natural history of acid-related diseases, while endocrine cell changes are mostly secondary to gastritis-related gland atrophy and have no tumorigenic potential.

Localization of bombesin and GRP (gastrin releasing peptide) sequences in gut nerves or endocrine cells.

SummaryFive anti-gastrin releasing peptide (GRP) sera have been characterized against GRP, bombesin and related polypeptides spotted on cellulose acetate discs. Antibodies reacting with the C-terminal G-14 sequence of bombesin and the 19–27 sequence of GRP, were detected in all sera. Antibodies directed exclsively against the bombesin unrelated 1–17 sequence of GRP were found only in one serum (R-6902). With parallel immunohistochemical tests only the C-terminal immunoreactivity was detected in endocrine-paracrine cells of the chicken proventriculus, while both immunoreactivities were present in nerve fibres and a few nerve cell bodies of the mammalian gut. The distribution of GRP- and bombesin-like immunoreactive nerves in the gastric mucosa of both pyloric and oxyntic type the submucosal and myenteric plexus along the whole gastrointestinal wall and at sphincter regions is detailed.

Genetic pattern, histological structure, and cellular phenotype in early and advanced gastric cancers: Evidence for structure-related genetic subsets and for loss of glandular structure during progression of some tumors

Gastric cancer shows remarkable heterogeneity in histological pattern, cellular phenotype, and genotype. Tumor subsets identified by varying procedures have shown limited reciprocal correlation and have failed to provide a sound rationale for the characterization and classification of all tumors. Based on a case series of 130 gastric cancers that covered both early (70 cases) and advanced (60 cases) stages and that represented most histological types and structural patterns, this study investigated (1) microsatellite instability and p53 gene mutation by means of PCR-based molecular techniques and (2) p53 protein accumulation or tumor cell immunophenotype by means of immunoperoxidase procedures. It was found that microsatellite instability and p53 gene mutation involve two distinct subsets of both early and advanced-stage glandular (intestinal) cancer, and that, contrastingly, they leave purely diffuse cancers unaffected. Mixed cancers, namely, those in which glandular admixed with diffuse growths, showed scarce microsatellite instability at all stages, whereas prominent p53 gene mutation and p53 protein accumulation was limited to the advanced stage alone. No significant correlation was found between tumor cell immunophenotype and either genotype or histotype, although some correlation with particular structural patterns was detected. Comparison of intramucosal with invasive growths within any given tumor suggested that invasive cancers with diffuse-type growth arise in part from mucosal cancers of glandular or mixed structure through progressive loss of intercellular junctional systems. It is concluded that at least two genetically distinct subsets of glandular cancer, one with microsatellite instability and the other with p53 lesions, should be separated both from purely diffuse cancer and, at least in the advanced stage, from mixed cancer. Available evidence suggests distinct clinicopathologic profiles for such tumor entities.