concanavalin-a and Metaplasia

The molecular mechanisms underlying the development of intestinal metaplasia (IM) of the human stomach have yet to be clarified in detail. Besides ectopic expression of intestinal transcription factors, Cdx1 and Cdx2, little information is available regarding other regulatory factors. Hence, we here analyzed Sox2, a human homolog of a chicken gastric transcription factor, with reference to our new classification for gastric/intestinal (GI)-mixed type IM.. Twenty specimens of surgically resected antral mucosa were subjected to a gland isolation technique. Isolated glands were classified into gastric (G), GI-mixed, and solely intestinal (I) types according to Alcian blue and paradoxical concanavalin A staining and were quantified for mRNA levels of gastrointestinal markers.. MUC5AC and MUC6 transcripts decreased with the progression of IM, while MUC2 and villin-1 were inversely correlated. Sox2 showed a gradual decrease from G, through GI, to the I type (G vs GI and GI vs I, P<0.01 and P<0.005, respectively). On the other hand, Cdx1 (G vs GI and GI vs I, P<0.0001 and P=0.337, respectively) and Cdx2 (G vs GI and GI vs I, P<0.0001 and P<0.05, respectively) appeared in IM. Immunohistochemical study confirmed decreased expression of Sox2 and ectopic emergence of Cdx2 protein in IM glands.. Down-regulation of Sox2, besides ectopic expression of Cdx genes, may be important factors for the development of IM.

Topics: Avian Proteins; Concanavalin A; Disease Progression; DNA-Binding Proteins; Down-Regulation; Gastric Mucosa; Gene Expression Regulation, Neoplastic; HMGB Proteins; Homeodomain Proteins; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Metaplasia; Mucin 5AC; Mucin-5B; Mucin-6; Mucins; Nuclear Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; SOXB1 Transcription Factors; Stomach Neoplasms; Transcription Factors

Histopathological and lectin-histochemical characteristics were studied in the lining epithelium of postoperative maxillary cysts (POMC).. Histological (HE, PAS, AB), immunohistochemical (CD3 and L26) and lectin (wheat germ agglutinin, WGA; Ulex europaeus agglutinin I, UEA-I; concanavalin A, ConA) stainings were performed in the 360 POMC specimens. The number of goblet cells and inflammatory cells was counted and statistically analyzed.. The lining epithelium was classified into three types based on histopathological characteristics; pseudostratified ciliated epithelium (pSCE), transitional epithelium (TE) and stratified squamous epithelium (SSE). Local infiltration of inflammatory cells into the cyst wall was associated with an increased number of goblet cells in the lining epithelium. The observed association between the infiltration of inflammatory cells and an increase in the number of goblet cells was statistically significant in groups with lining pSCE and TE. Glycoconjugate histochemical analysis revealed that the surfaces of the lining epithelium with squamous metaplasia showed an increased degree of staining reactivity with UEA-I, whereas the staining reactivity with ConA was reduced. Goblet cells were able to be stained with WGA and UEA-I, but showed extremely low reactivity with ConA.. Changes in the glycoconjugate expression of the metaplastic lining epithelium and goblet cell development play an important role in the local defense mechanisms against inflammatory factors in POMC.

Topics: Adult; Aged; Aged, 80 and over; Alcian Blue; Analysis of Variance; B-Lymphocytes; Cilia; Coloring Agents; Concanavalin A; Epithelial Cells; Epithelium; Female; Fluorescent Dyes; Goblet Cells; Humans; Immunohistochemistry; Jaw Cysts; Linear Models; Male; Maxillary Diseases; Metaplasia; Middle Aged; Neutrophils; Periodic Acid-Schiff Reaction; Plant Lectins; Plasma Cells; Postoperative Complications; T-Lymphocytes; Wheat Germ Agglutinins

We report a rare case of pyloric gland-type tubular adenoma of the main pancreatic duct. It was a grossly visible polypoid nodule and was composed of closely packed pyloric-type glands. This adenoma was present within an intraductal papillary mucinous adenoma (IPMA). In this IPMA lesion, aggregations of pyloric-type glands were occasionally observed, and most of the cells including ductal lining cells expressed pyloric gland-type mucin. The IPMA of the present case showed more extensive pyloric gland metaplasia or differentiation than commonly noted in IPMAs. We consider this pyloric gland-type tubular adenoma to be derived from a selective growth of IPMA cells showing pyloric gland metaplasia.

Topics: Adenoma; Aged; Antibodies, Monoclonal; Concanavalin A; DNA, Neoplasm; Exocrine Glands; Gallstones; Gastric Mucosa; Genes, ras; Humans; Immunohistochemistry; Male; Metaplasia; Mucins; Mutation; Neoplasms, Second Primary; Pancreatic Ducts; Pancreatic Neoplasms; Polymerase Chain Reaction

The specificity of monoclonal antibodies against gastric mucins (designated as HIK1083, PGM 36, and PGM 37) was studied immunohistochemically in normal, metaplastic, and neoplastic human tissues. These antibodies labeled class III mucin-producing cells identified by paradoxical concanavalin A staining in normal stomach, duodenum (Brunner gland), biliary tract, and main pancreatic duct; in mucinous metaplasia of pancreas and gallbladder; and in adenocarcinomas of stomach (90%), bile duct (80%), gallbladder (100%), pancreas (80%), lung (100% of goblet cell type adenocarcinomas), ovary (67% of mucinous carcinomas), and uterine cervix (100% of adenoma malignum tumors). Normal and neoplastic cells of esophagus, colon, salivary gland, kidney, endometrium, breast, prostate, and liver, as well as normal small intestine, lung, and uterine cervix, were all negative. The antibodies used should be valuable for the detection of class III mucin and class III mucin-producing cells in normal, metaplastic, and neoplastic tissues.

Topics: Antibodies, Monoclonal; Cell Line; Concanavalin A; Female; Gastric Mucosa; Humans; Male; Metaplasia; Mucins; Neoplasms; Reference Values; Staining and Labeling

Signet ring cell carcinomas of the stomach are thought to arise from the proper gastric mucosa without intestinal metaplasia. It was recently reported that intestinal phenotypes appear along with tumor progression. In this study, we performed several experiments to reconsider the significance of this intestinalization in the growth of signet ring cell carcinoma. We applied mucin histochemistry with monoclonal antibodies MUC2 (Ccp58) and M1 (45M1), and paradoxical concanavalin A staining for class III mucin [PCS(III)] reaction to 29 intramucosal and 25 deeply invasive carcinomas of this type and correlated the phenotypic expression with the size of the mucosal spread and the depth of tumor invasion. It was found that the larger the size of the mucosal lesion, the more frequently the intestinal phenotypes were demonstrated. There was no significant increase in the expression of the intestinal phenotype as the tumor invaded the deeper part of the mucosa or as the intestinal metaplasia increased in the background mucosa. The intestinal expression appeared to be suppressed in the earlier phase of deep invasion. In the mucosal part of the tumor, the intestinal phenotype was often expressed regionally and incompletely, coexisting with gastric phenotypes at the cellular and the tissue levels. These findings indicate that the expression of the intestinal phenotype is a time-dependent and unstable phenomenon probably based on the accumulation of genetic changes and plays a neutral role in progression of signet ring cell carcinomas.

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoma, Signet Ring Cell; Concanavalin A; Female; Gastric Mucosa; Humans; Immunohistochemistry; Intestinal Mucosa; Intestines; Male; Metaplasia; Middle Aged; Mucins; Neoplasm Invasiveness; Phenotype; Stomach Neoplasms

Mucinous tumors of the ovary have been thought to originate in two ways: by müllerian-type metaplasia of surface epithelium, and as monodermal teratomas. To gain a better understanding of their pathogenesis, the authors analyzed these tumors for their expression of estrogen receptors (ER) and progesterone receptors (PR) as markers of müllerian-type differentiation and for their content of gastric-type mucin as a marker of gastric differentiation.. The histochemical expression of ER, PR, and gastric-type mucin was studied in 10 specimens of the cervix with normal endocervical glands (as a representative of müllerian-derived mucin-containing cells), 3 ovary specimens with surface epithelial inclusion cysts that contained endocervical-like mucin-containing cells (representing müllerian-type metaplasia), and 47 mucinous tumors of the ovary (29 benign, 8 with low malignant potential, and 10 malignant).. Normal endocervical glands expressed ER and PR and rarely expressed gastric-type mucin. Ovarian inclusion cysts showed strong expression of ER and PR in the cuboidal cells and drastically reduced expression in the endocervical-like mucin-containing cells. The cuboidal cells were negative for gastric-type mucin, but the endocervical-like mucin-containing cells expressed gastric-type mucin. Endocervical-like mucinous cells in benign and borderline mucinous tumors showed expression of PR and/or gastric-type mucin in all cases.. The staining results for the inclusion cysts support the thesis that the endocervical-like mucinous cells encountered in the ones that express ER and PR weakly or not at all and have histochemical properties of normal gastric epithelium have their origin in metaplasia of müllerian-type epithelium. Application of the same staining methods to benign ovarian tumors and those with low malignant potential suggests strongly that similar müllerian-type metaplasia is a major pathway in their pathogenesis.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Cell Differentiation; Cell Transformation, Neoplastic; Cervix Uteri; Concanavalin A; Cystadenoma, Mucinous; Female; Galactose Oxidase; Gastric Mucins; Humans; Immunohistochemistry; Metaplasia; Middle Aged; Mullerian Ducts; Ovarian Cysts; Ovarian Neoplasms; Receptors, Estrogen; Receptors, Progesterone; Staining and Labeling

Phenotypic expression of tumor cells was investigated in 33 early gastric carcinomas by mucin histochemistry using paradoxical concanavalin A staining. This staining method had been developed to differentiate 3 classes of mucins located at various sites of the alimentary tract. Twenty-five (76%) tumors contained mixtures of neutral or acid class II mucin and class III mucin, suggesting the origin of multipotential stem cells. The surface mucous cell expression was more dominant than the pyloric gland or intestinal phenotypes in the well-and poorly differentiated adenocarcinomas. The intestinal properties of the tumor cells were noted not only in the well-differentiated but also in the poorly differentiated or signet ring cell carcinomas, not closely being related to the presence of background intestinal metaplasia. Signet ring cell carcinomas revealed a distinct pattern of mucin histochemistry compared with the other types.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Cell Differentiation; Concanavalin A; Histocytochemistry; Humans; Intestines; Metaplasia; Mucins; Staining and Labeling; Stem Cells; Stomach Neoplasms

Squamous metaplasia of tracheal mucosa, putative preneoplastic lesions, involves replacement of normal mucociliary epithelium with epidermoid lesions. Alterations in cell differentiation and neoplasia accompany changes in glycoconjugates at the plasma membrane. Lectins which bind to specific cell surface glycoconjugates are used to elucidate such alterations. We have used peanut agglutinin (PNA) and concanavalin A (Con A) as specific molecular probes to elucidate cell specific alterations in the development and progression of squamous metaplasia in the hamster tracheal explants induced by benzo[a]pyrene (BP), a component of cigarette smoke. The tracheal explants were cultured in serum-free chemically defined medium and treated with BP (7.5 micrograms/ml) for up to 15 days. At this time, 80-90% of the carcinogen treated explants exhibited epidermoid lesions at various stages of development. The untreated control explants maintained normal pseudostratified epithelium. In these explants, PNA and Con A exhibited moderate reaction in the cytoplasm of luminal mucociliary cells; the basal cells showed no reaction. In early metaplastic lesions PNA and Con A stained only the cytoplasm of luminal cells; the metaplastic cells along the basal lamina were negative. In well-developed lesions, in which the luminal mucociliary layer was still intact overlying the lesions, the metaplastic epithelium remained unreactive with the lectins. In highly advanced lesions exhibiting cornification, and in which the mucociliary layer was sloughed, the metaplastic lesions showed strong reaction with both the lectins. The reaction was limited mainly to the plasma membrane of the metaplastic cells. These results show that induction and progression of the BP induced lesions accompany dynamic cell specific alterations in glycoconjugates. The epidermoid lesions acquire glycoconjugates rich in beta-D-galactose and D-mannose. These results are also consistent with the basal cell origin of the metaplastic lesions.

Topics: Animals; Benzo(a)pyrene; Cell Membrane; Concanavalin A; Cricetinae; Culture Techniques; Glycoconjugates; Lectins; Mesocricetus; Metaplasia; Peanut Agglutinin; Precancerous Conditions; Trachea; Tracheal Neoplasms

Intestinal metaplasia of the stomach was grouped into 3 subtypes (A, B and C) according to the degree of pyloric gland involution which was judged from patterns of paradoxical Concanavalin A staining after Katsuyama and Spicer. The appearance of endocrine cells was investigated with immunohistochemical and silver methods. Type A metaplasia with slightly to moderately atrophic pyloric glands corresponded to the incomplete type in the previous classification, while Type C showing complete disappearance of pyloric glands corresponded to the complete type. Type B with severely atrophic pyloric glands was an intermediate. This subtyping reflects the cell kinetics in the intestinalized mucosa well. Regarding the endocrine cells, their total number varied in the order Type A greater than Type B greater than Type C. The selective populations of the endocrine cells including glicentin-containing cells, Grimelius-positive argyrophil cells without argentaffinity and intestinal-type enterochromaffin cells frequently formed hyperplastic foci in the intestinalized areas, where the other gut-type and proper gastric-type endocrine cells were scarcely noted. Immunoreactivity of glucagon or bovine pancreatic polypeptide were occasionally identified in a subpopulation of the glicentin-containing cells.

Topics: Adult; Aged; Atrophy; Concanavalin A; Enterochromaffin Cells; Gastric Mucosa; Glucagon; Histocytochemistry; Humans; Intestinal Mucosa; Metaplasia; Middle Aged; Pancreatic Polypeptide; Proglucagon; Protein Precursors; Pyloric Antrum; Staining and Labeling