bromochloroacetic-acid and Crohn-Disease

Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Crohn Disease; Duodenal Neoplasms; Female; Humans; Ileal Neoplasms; Jejunal Neoplasms; Keratins; Male; Metaplasia; Middle Aged; Mucins; Stomach Neoplasms

Topics: Alleles; Animals; Crohn Disease; Diabetes Mellitus, Type 2; Disease; DNA; Evolution, Molecular; Female; Genome, Human; Humans; Interleukin-18; Keratins; Liver Cirrhosis, Biliary; Male; Neanderthals; Optic Disk; Sequence Analysis, DNA; Smoking

We have identified miss-sense mutations in keratin 8 in a subset of patients with inflammatory bowel disease (Crohn disease and ulcerative colitis). Inflammatory bowel diseases are a group of disorders that are polygenic in origin and involve intestinal epithelial breakdown. We investigated the possibility that these keratin mutations might contribute to the course of the disease by adversely affecting the keratin filament network that provides mechanical support to cells in epithelia. The mutations (Gly62 to Cys, Ile63 to Val and Lys464 to Asn) all lie outside the major mutation hotspots associated with severe disease in epidermal keratins, but using a combination of in vitro and cell culture assays we show that they all have detrimental effects on K8/K18 filament assembly in vitro and in cultured cells. The G62C mutation also gives rise to homodimer formation on oxidative stress to cultured intestinal epithelial cells, and homodimers are known to be polymerization incompetent. Impaired keratin assembly resulting from the K8 mutations found in some inflammatory bowel disease patients would be predicted to affect the maintenance and re-establishment of mechanical resilience in vivo, as required during keratin cytoskeleton remodeling in cell division and differentiation, which may lead to epithelial fragility in the gut. Simple epithelial keratins may thus be considered as candidates for genes contributing to a risk of inflammatory bowel disease.

Topics: Actin Cytoskeleton; Animals; Antibodies, Monoclonal; Base Sequence; Cell Differentiation; Chromosomes, Human, Pair 12; Colitis, Ulcerative; Crohn Disease; Dimerization; Electrophoresis, Polyacrylamide Gel; Humans; Inflammation; Inflammatory Bowel Diseases; Keratin-8; Keratins; Mice; Models, Genetic; Molecular Sequence Data; Mutation; Oxidative Stress; Polymers; Protein Binding; Protein Conformation; Sequence Analysis, DNA; Time Factors; Transfection; Xenopus

The nuclear DNA contents of atypical mesothelial cells from five patients who had an eosinophilic pleural effusion (EPE) were studied by the use of DAPI (4',6-diamidino-2-phenylindole dihydrochloride) DNA staining. Analysis of the nuclear DNA content revealed a polyploid pattern, with a major peak in the tetraploid region. Using an immunocytochemical technique, the atypical mesothelial cells showed a positive reaction for cytokeratin. In contrast carcinoembryonic antigen (CEA) was always negative in these cells. It is suggested that the atypical mesothelial cells with EPE had a higher rate of proliferation than did the normal mesothelial cells.

Topics: Adult; Aged; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Cell Division; Cell Nucleus; Crohn Disease; DNA; Eosinophilia; Epithelium; Female; Humans; Indoles; Keratins; Lung Neoplasms; Male; Mediastinal Cyst; Membrane Glycoproteins; Mucin-1; Pleural Effusion; Pneumonia; Pneumothorax; Polyploidy

IgG1 and activated complement are colocalised on the colonic epithelial brush border in active ulcerative colitis. To investigate whether such deposition is specific for ulcerative colitis, we examined ethanol fixed mucosal specimens from 18 patients with Crohn's colitis and 14 with terminal ileitis by indirect two colour immunofluorescence staining. Monoclonal antibodies to the IgG subclasses and to neoepitopes of activated complement C3b and the terminal complement complex were used in combination with rabbit antiserum to C1q, C4c or cytokeratin. Granular deposition of C3b and terminal complement complex were observed at the luminal face of the surface epithelium in 10 of 18 patients with Crohn's colitis. Specimens from eight of 14 patients with ileal involvement were intensely stained for activated complement (primarily C3b) within the surface mucus layer. No epithelial IgG, C1q or C4c deposition was observed. The results suggest that early and late phase complement activation takes place at the luminal face of the epithelium in Crohn's disease. The absence of colocalised IgG and complement components involved in the classical activation pathway (C1q and C4c), however, suggest that other immunopathological mechanisms (the alternative pathway?) are primarily involved in Crohn's disease in contrast with ulcerative colitis.

Topics: Adolescent; Adult; Colitis, Ulcerative; Colon; Complement Activation; Complement C3b; Complement C4; Complement C4b; Complement Membrane Attack Complex; Crohn Disease; Epithelium; Female; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Intestinal Mucosa; Keratins; Male; Middle Aged; Peptide Fragments

We present two cases of small-bowel adenocarcinoma and dysplasia in patients with longstanding Crohn's disease. In one case, the dysplasia and cancer were exclusively located in the terminal ileum, whereas in the other case, several cancers were found from the ileum toward the transverse colon. In both cases, we found a clinically unsuspected Dukes C1 mucinous adenocarcinoma together with large foci of polypoid villous dysplasia or with multifocal high-grade dysplasia and intramucosal carcinoma. Immunohistochemical staining for carcinoembryonic antigen (CEA) revealed a different staining pattern in various diseased areas. The intensity of CEA staining paralleled the histologic degrees of dysplasia and neoplasia. Cytokeratin expression was disturbed in inflamed mucosa, and it was more pronounced in high-grade dysplasia and invasive carcinoma. We conclude that the presence of dysplasia in an intestinal biopsy of a patient with Crohn's disease should arouse the pathologist's suspicion of carcinoma and force him or her to take multiple sections from strictures and polypoid lesions, especially since the clinical symptoms of a carcinoma may be obscured by the symptoms of inflammatory bowel disease. Immunohistochemical staining with CEA and cytokeratin are useful in the objectivation of dysplasia.

Topics: Adenocarcinoma; Adult; Carcinoembryonic Antigen; Colitis; Colonic Neoplasms; Crohn Disease; Female; Humans; Ileal Neoplasms; Ileitis; Intestinal Mucosa; Keratins; Male; Middle Aged; Neoplasm Invasiveness

A high prevalence of antibodies to cytoskeleton components (anti-CYTO) and of anti-smooth muscle (SMA) and antinuclear (ANA) antibodies has been found in inflammatory bowel disease (IBD). In particular, a significant correlation has been documented between anti-CYTO and activity of the disease in ulcerative colitis and anti-fibroblast intermediate filaments (anti-vimentin) antibodies and Crohn's disease. The antibodies are detectable in the three major immunoglobulin classes, including IgA. While titres of anti-CYTO did not exceed 1:40, ANA and SMA were of high titres (up to 1:1,280). Antibodies to epithelial cells intermediate filaments (anti-cytokeratin) were detected only occasionally. The significance of these findings in IBD is discussed.

Topics: Adolescent; Adult; Aged; Antibodies; Antibodies, Antinuclear; Autoantibodies; Colitis, Ulcerative; Crohn Disease; Cytoskeleton; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Keratins; Male; Microtubules; Middle Aged; Muscle, Smooth; Vimentin