oxyntomodulin and Adenocarcinoma

The occurrence of endocrine cells in 350 cases of colorectal adenocarcinoma was studied by immunohistochemistry for chromogranin A (CGA). The hormone profile of endocrine tumor cells, the correlation between endocrine differentiation and presence of other colorectal epithelial-cell lineages and the prognostic relevance of endocrine differentiation in colorectal cancer were investigated. CGA-positive tumor cells were found in 30% of cases, 21% showing moderate positivity and 9.0% extensive positivity. Of CGA-positive tumors, 70% additionally produced neurohormones, mainly indigenous to normal colorectal epithelium: 55% showed immunoreactivity for glucagon-like substances, 20% for serotonin and 10% for somatostatin, PYY and HCG. No immunoreactivity was found for various neurohormones not normally produced by colorectal endocrine cells. CGA-positive tumors tended to be more aggressive than CGA-negative tumors. Especially, tumors with extensive CGA positivity showed shorter survival, which was most apparent within Dukes' stage C. In multivariate analysis, extensive CGA positivity was an independent indicator of poor prognosis. CGA immunoreactivity significantly correlated with mucin production, but not with expression of secretory component (SC), a columnar-cell marker. Mucin production significantly correlated with SC expression. Tumors positive for CGA but not for mucin and/or SC showed the worst prognosis. SC expression was a relatively favorable feature, and mucin-producing tumors showed intermediate behavior.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Chromogranin A; Chromogranins; Colonic Neoplasms; Cytoplasm; Endocrine Glands; Female; Follow-Up Studies; Glicentin; Glucagon; Glucagon-Like Peptides; Humans; Male; Middle Aged; Neoplasm Staging; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Rectal Neoplasms; Serotonin; Somatostatin; Survival Analysis

It has been shown in several studies that a colonic J-pouch obviates much of the early dysfunction after a low anterior resection in terms of urgent and frequent bowel movements. In search for specific mediators of the postoperative functional adaptation, two gut peptides, peptide YY and enteroglucagon, were studied. Plasma and "neorectal" mucosal levels of both peptides were measured in 12 patients with a straight coloanal anastomosis and in 11 patients with a colonic J-pouch anastomosis. Patients were part of a randomized trial comparing straight and colonic pouch anastomosis. Fasting plasma samples of both peptides were collected intraoperatively, after one week, before loop ileostomy closure, and at 1, 3, and 12 months after loop ileostomy closure.. There was no difference between the straight and the pouch groups in plasma concentrations of either peptide at any time period postoperatively. The only longitudinal hormonal changes were transient increases in mucosal peptide YY content at one-month follow-up and in mucosal enteroglucagon content before loop ileostomy closure.. Peptide YY and enteroglucagon responses in these patients appear not to be major factors for improved outcome after formation of a colonic pouch in low anterior resection.

Topics: Adaptation, Physiological; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Ileostomy; Intestinal Mucosa; Male; Middle Aged; Peptide YY; Peptides; Proctocolectomy, Restorative; Rectal Neoplasms

To elucidate the biological and clinicopathological significance of endocrine differentiation in gastric adenocarcinoma, an immunohistochemical study was made of 127 cases with ascertained five-year survivals, and of 45 recent cases of bromodeoxyuridine (BrdU) labeling. Endocrine differentiated cancer cells were demonstrated in 37 out of the 127 cases (29.1%) evaluated by chromogranin A (CGA) immunoreactivity, and all CGA-positive tumors were classified as advanced gastric cancer. Analysis of retrospective five-year survival rates revealed the adenocarcinomas with endocrine differentiation to have had significantly longer survival times than those without endocrine immunoreactivity in stage II, but not in stages III or IV. Double immunolabeling for CGA and BrdU in the other 45 adenocarcinoma cases showed only a single CGA-positive cancer cell with BrdU incorporation among a total of 454 CGA-positive cells examined. There was no significant difference between the labeling indices of the general cancer population and the cancer cells adjacent to CGA-positive cells. In conclusion, endocrine differentiation of gastric cancer is not uncommon, particularly in advancing cancer, and it would be a useful marker for a better prognosis in stage II. Probably, endocrine differentiated cancer cells are almost dormant with virtually no DNA synthesizing activity, and their paracrine effect is most unlikely to work in vivo.

Topics: Adenocarcinoma; Bromodeoxyuridine; Cell Differentiation; Cell Division; Chromogranin A; Chromogranins; Gastrins; Glicentin; Glucagon; Glucagon-Like Peptides; Glycoprotein Hormones, alpha Subunit; Hormones; Humans; Immunohistochemistry; Lymph Nodes; Lymphatic Metastasis; Peptide Fragments; Protein Precursors; Serotonin; Somatostatin; Stomach Neoplasms

Gut endocrine cells in a total of 122 intestinal-tract adenocarcinomas induced in inbred Wistar rats by 1,2-dimethylhydrazine dihydrochloride were examined histologically, ultrastructurally, and immunohistochemically for gastrin, somatostatin, vasoactive-intestinal polypeptide (VIP), and glicentin (enteroglucagon). Of the 122 tumors, argyrophil cells were detected in 42 tumors (34.3%) comprising 15 tumors of the well differentiated type and 27 tumors of the poorly differentiated type, including signet-ring-cell carcinomas. Of the 27 tumors of the poorly differentiated type, 12 were regarded as endocrine-cell carcinomas composed of numerous argyrophil or argentaffin cells and mucus-containing cells. Immunohistochemically, 7 of the 12 tumors had glicentin and two of these seven tumors also had gastrin and argentaffin cells synchronously. None of the tumors showed immunoreactivity for somatostatin and VIP. Nine of the 12 tumors metastasized to the lung, pancreas, liver, mesenterium, omentum, and lymph nodes. The metastatic foci of these tumors were also shown to have glicentin and argentaffin cells. Ultrastructurally, four types of endocrine granule were found in the tumor cells and amphicrine cells containing endocrine granules and mucous granules were noted. These endocrine-cell tumors were assumed to develop from totipotent immature cells of endodermal origin.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Carcinogens; Chromaffin System; Dimethylhydrazines; Enterochromaffin Cells; Female; Gastrins; Glucagon-Like Peptides; Intestinal Neoplasms; Male; Microscopy, Electron; Neoplasm Metastasis; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Somatostatin; Vasoactive Intestinal Peptide

In a consecutive material consisting of 24 stomachs resected due to adenocarcinoma, intestinal metaplasia occurred in 21. Gastrin-producing cells (G-cells) were found to be distributed in a sporadic manner in antra with intestinal metaplasia. Not a single G-cell could be demonstrated in areas with metaplasia, while in the nonmetaplastic areas the distribution of the G-cells corresponded to that of the middle part of the mucosa. This means, that an error can occur when determining the quantity of G-cells, and can explain the previous controversial results regarding the density of G-cells. Enteroglucagon containing cells (GLI-cells) on the contrary were demonstrated in areas with intestinal metaplasia in antra of 19 of the stomachs showing intestinal metaplasia but never in the nonmetaplastic mucosa. This indicated that metaplasia also includes the endocrine cells. The identification of the G-cells and the GLI-cells was carried out by means of indirect immunoperoxidase technique combined with alcian blue pH 2,6-PAS staining.

Topics: Adenocarcinoma; Cell Count; Gastrins; Glucagon-Like Peptides; Humans; Metaplasia; Pyloric Antrum; Stomach Neoplasms