gastrins and Adenocarcinoma--Mucinous

Gastrin producing ovarian tumor is a rare cause of the Zollinger-Ellison syndrome. We report the case of an ovarian carcinoma showing increased plasma gastrin concentration. A 60-yr-old woman presented with epigastric pain and diarrhea. Physical examination showed a large mass in the lower abdomen. Computed tomography revealed a large multilocular ovarian cyst. Upper gastrointestinal endoscopy examination showed multiple ulcerations of the stomach and duodenum. The plasma gastrin level was 1500 pg/ml. No tumors were found in the pancreas and duodenum, and salpingo-oophorectomy was performed. Histologic examination revealed a mucinous tumor of borderline malignant potential. Immunoperoxidase studies for gastrin showed many gastrin-producing cells within the epithelium of the tumor. There have been 11 cases (including our patient) of gastrin-producing ovarian tumor reported in the literature. We review here the relevant literature. Although ovarian gastrinoma is extremely rare, it should be considered as a possible cause of the Zollinger-Ellison syndrome in women.

Topics: Adenocarcinoma, Mucinous; Female; Gastrins; Hormones, Ectopic; Humans; Middle Aged; Ovarian Neoplasms; Zollinger-Ellison Syndrome

It has been assumed that gastrin stimulates the growth of pancreatic cancer in an autocrine way through co-expression of gastrin and the cholecystokinin-B receptor (CCK-BR). However, pancreatic cancer cell lines established directly from patients have revealed a great heterogeneity in cell proliferation when exposed to CCK, gastrin and their receptor antagonists. The aim of this study was therefore to examine co-expression of CCK-A and CCK-B receptor (CCK-AR and CCK-BR), and gastrin mRNA as well as the secretion of CCK and gastrin peptides in these cell lines.. Fourteen cell lines were established from primary pancreatic cancers or their metastases. Total RNA was isolated from the cell lines and reverse-transcribed into single-stranded cDNA. A PCR technique based on Taq polymerase-antibody interaction and CCK-AR, CCK-BR and gastrin-specific primers, followed by Southern blot analysis, were the methods used. The incubation mediums were analysed for the presence of secreted CCK/proCCK and gastrin/progastrin peptides by specific radioimmunoassays (RIA).. By means of nested Reverse-Transcribed Polymerase Chain Reaction (nested RT-PCR), combined with Southem blot analysis of the PCR amplified products, CCK-AR and gastrin mRNA co-expression was detected in cell lines LPC-6p and LPC-10m, whereas CCK-BR and gastrin mRNA could be detected in cell lines LPC-8p and LPC-12m. A low level of secreted CCK peptides was detected in cell line LPC-6p, which also expressed CCK-AR mRNA. In no other cases were CCK or gastrin peptides detected in the cell culture mediums.. The lack of CCK-BR and gastrin mRNA co-expression, and not detectable levels of secreted CCK and gastrin in culture media, does not lend support to the hypothesis that concomitant gene-expression of CCK receptors and gastrin or CCK are essential to maintaining pancreatic cancer cell proliferation.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Biopsy; Blotting, Southern; Carcinoma, Ductal, Breast; Carcinoma, Papillary; Cell Division; Cholecystokinin; Gastrins; Gene Expression Regulation, Neoplastic; Humans; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Radioimmunoassay; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

The endocrine cells in intraductal papillary-mucinous neoplasms (IPN) of the pancreas have rarely been investigated. In the normal pancreatic ducts of normal pancreases (n = 5) there were a few endocrine cells: argyrophil in 5 (100%), chromogranin A in (100%), pancreatic polypeptide (PP) in 3 (60%), and insulin in 7 (20%). These endocrine cells were scattered, and located in the basal portions of pancreatic ducts. In IPN of the pancreas (n = 9), there were many endocrine cells: argyrophil in 7 (78%), argentaffin in 8 (89%), chromogranin A in 8 (89%), PP in 7 (78%), serotonin in 7 (78%), insulin in 4 (44%), and gastrin in 5 (56%). In invasive ductal adenocarcinoma of the pancreas (n = 6), many endocrine cells were also detected: argyrophil cells in (67%), chromogranin A in 3 (50%), insulin in 3 (50%), glucagon in 4 (67%), and somatostatin in 3 (50%). In positive cases, endocrine cells were situated under or among the neoplastic cells and the proportion of endocrine cells in IPN was less than 5% of the total neoplastic cell population. These data show that normal pancreatic ducts contain endocrine cells and that IPN frequently contain argyrophil, argentaffin, chromogranin A, and hormone-containing endocrine cells. These data also suggest that endocrine differentiation occurs during neoplastic transformation and progression of IPN of the pancreas.

Topics: Adenocarcinoma, Mucinous; Adenoma; Aged; Aged, 80 and over; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Chromogranin A; Chromogranins; Enterochromaffin Cells; Female; Gastrins; Glucagon; Histocytochemistry; Humans; Immunohistochemistry; Insulin; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Serotonin; Vasoactive Intestinal Peptide

Endocrine cells (EC) were found in 19 out of 42 cases of the pancreas carcinoma (42.5%). Among them, 4 cases had a positive rate of EC more than 50%. The positive rate of EC in the well differentiated carcinomas (5/20) was lower than that of the poorly-differentiated ones (12/19) or mucinous carcinoma (2/2), and the positive rate in histologic grade I cases (5/18) was significantly lower than that of the grade III cases (7/8). The number of mast cells infiltrating in the matrix in EC positive cases was significantly higher than that of the negative ones. The positive rate of EC in the cases with metastasis (8/14) was higher than that of the non-metastasis cases (7/21). Immunocytochemical staining showed that GN (8), SS(4), HCG(5), CK(12), EMA(13) and CEA(9) were positive in 19 EC positive cases.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Female; Gastrins; Humans; Keratins; Male; Middle Aged; Neurosecretory Systems; Pancreatic Neoplasms

One hundred and twenty-eight cases of gastric carcinoma were examined with immunohistochemical technic for carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), serotonin, gastrin and lysozyme. CEA were observed in 105 cases. Twenty-four cases were positive for HCG, 53 cases for serotonin, 31 cases for gastrin, 89 cases for lysozyme. Sixty-nine cases exhibited more than two hormones or one hormone and lysozyme simultaneously in different cells of the same tumor. Ultrastructurally, sometimes three types of secretory granules were noticed. The electron dense granules in the lysozyme-containing tumor cells were similar to those of Paneth's cells in intestinal metaplasia. The positive rates of the above three hormones, lysozyme and multi-marker expression in diffuse type carcinoma were higher than those in intestinal type, and 42/44 cases of the diffuse type carcinoma were histologically undifferentiated carcinomas or signet-ring cell carcinomas. Lymph node metastasis occurred more frequently in those carcinomas with hormone or lysozyme positivity. These findings suggest that these neoplastic endocrine cells and Paneth's cells have originated from multipotential differentiation of neoplastic stem cells in the stomach, reflecting the state of the gene activity in the tumor cells.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoembryonic Antigen; Carcinoma; Chorionic Gonadotropin; Gastrins; Humans; Immunohistochemistry; Lymphatic Metastasis; Muramidase; Neoplasm Staging; Serotonin; Stomach Neoplasms

1,351 specimens resected surgically from 100 patients with gastric carcinoma were studied with PAP immunoperoxidase and ultrastructural method. The tumor cells were found positive for gastrin, serotonin, somatostatin and argyrophil particles in 19 patients. Among them the gastrin-secreting tumor cells consisted of 50% of the total in 4 cases, representing a separate new subtype, neuro-endocrine (NE) gastric carcinoma. Of the 100 cases, 16 (32%) contained NE cells among 50 undifferentiated type, while only 3 cases (6%) contained NE cells among the remaining 50 cases, the well-differentiated type. These results suggest that the appearance of NE tumor cells is closely correlated with the degree of differentiation of cancer, and confirms theoretically the heterogenicity of gastric carcinoma, and further supports the concept that exocrine and endocrine type gastric cancer cells are isogenous, i.e., from the endodermal stem cells.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Female; Gastrins; Humans; Immunohistochemistry; Male; Middle Aged; Serotonin; Somatostatin; Stomach Neoplasms

Three hundred and one gastric cancer patients have been examined preoperatively to investigate their gastric acid secretions after stimulation by tetragastrin, and serum gastrin stimulation by a test meal, as well as for skin reactions and an evaluation of their serum glycoproteins. The results have indicated that their gastric secretions and serum gastrin response were found to be reduced, according to the advancement of their cancer, and that the gastric acid secretion of patients with signet ring cell carcinoma was higher than that of patients with other histological carcinomas. Gastric acid secretions of patients with an ulcerated type of cancer, that is, type IIc and type III in an early cancer stage and type IIc of an advanced Borrmann V type, was higher than in patients with other types, and there were significant correlationships between gastric secretions and PHA skin test and gastric secretions and the IAP and the sialic acid.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Female; Gastric Acid; Gastrins; Glycoproteins; Humans; Immunity, Cellular; Male; Middle Aged; Skin Tests; Stomach Neoplasms

Gastric acid secretions and serum gastrin levels have been examined in 128 patients with early gastric cancer and in 98 gastric ulcer patients. Gastric cancer patients were found to have lower acid secretions than did gastric ulcer patients, and those with elevated types of a differentiated adenocarcinoma had lower acid secretions than did those with depressed types of an undifferentiated adenocarcinoma. Gastric acid secretions in patients with both a gastric ulcer and cancer were found to decrease with aging. However, the serum gastrin levels were found to be decreased in patients with a gastric ulcer and to be increased in patients with a gastric cancer. Incidences of a differentiated adenocarcinoma increased with aging. From these observations, it has been speculated that the carcinogenesis of a differentiated adenocarcinoma may be related to increasing endogenous gastrin levels and decreasing gastric acid secretions. These results suggest that a continuous check of the serum gastrin levels might be a good marker for cancer detection and that gastrin antibodies might be useful for treatment.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Adult; Aged; Aging; Biomarkers, Tumor; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Stomach Neoplasms; Stomach Ulcer

Eight mucinous carcinomas of the breast were studied by light microscopy and immunohistochemistry; one was studied by electron microscopy. All 8 cases had abundant, relatively clear cytoplasm that contained mucin. Cells were argyrophil positive and argentaffin negative. Eight cases were positive for neuron specific enolase (NSE), 5 cases for serotonin, 1 case for serotonin and somatostatin and 2 cases for serotonin, somatostatin, and gastrin. None had clinical evidence of abnormal neuroendocrine function. Three patients had axillary lymph node metastases. Only 1 of 5 patients in whom there was clinical followup died of her disease. Electron microscopy of one case showed abundant intracytoplasmic and extracellular mucin, round and pleomorphic dense-core granules, numerous cell processes, and aggregates of intermediate filaments. These cases expand the histologic spectrum of breast carcinomas which may show neuroendocrine differentiation.

Topics: Adenocarcinoma, Mucinous; Breast Neoplasms; Cytoplasm; Gastrins; Histocytochemistry; Humans; Immunochemistry; Microscopy, Electron; Mucins; Neurosecretory Systems; Serotonin; Somatostatin

The localization of peptide hormones and serotonin in ovarian mucinous and endometrioid tumors with argyrophil cells was examined by immunohistochemistry. All of the 15 mucinous tumors had argyrophil cells which resemble the enterochromaffin cells seen in the gastrointestinal tract, and peptide hormones such as gastrin and somatostatin were found in 3 of 5 benign, in 3 of 5 borderline, and in all of 5 malignant tumors. Serotonin was found in 4 benign, 3 borderline and 2 malignant tumors. Of 19 endometrioid adenocarcinomas, type I argyrophil cells which resemble enterochromaffin cells were found in 4 tumors, type II argyrophil cells which contain argyrophil granules mainly in the apical portion or throughout the whole cytoplasm were found in 14, and mixed type cells were found in one. Somatostatin-positive cells were found only in type I cells of a tumor with mixed type argyrophil cells. Serotonin-positive cells were found in 3 tumors containing type I cells. The results obtained were discussed in the comparison with those of cervical and endometrial adenocarcinomas of the uterus. In conclusion, the present study suggests that type I or similar argyrophil cells in ovarian tumors may have endocrine activity.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Antibodies, Monoclonal; Endometriosis; Female; Gastrins; Glucagon; Histocytochemistry; Humans; Ovarian Neoplasms; Serotonin; Somatostatin

A total of 87 surgical cases of gastric carcinoma including 3 carcinoid tumors were investigated with the methods of silver reaction and immunoperoxidase stain for 8 different brain-gut hormones. Argyrophil (AP) cells were demonstrated in 38 cases (44%), argentaffin (AF) cells in 18 (21%) and endocrine cells in 13 (14%). The occurrence of endocrine cells had no relation with histological types. Glicentin cells were demonstrated in 10 cases, somatostatin in 7, motilin in 3, beta-endorphin in 2 and gastrin in one. Endocrine cells appeared generally in small numbers except one carcinoid tumor which had numerous somatostatin cells. No single cell positive for more than two kinds of hormones could be demonstrated. Two undifferentiated carcinomas looking like carcinoid tumors had argyrophil cells and endocrine cells of either somatostatin or beta-endorphin. These results suggest that carcinoid-like carcinoma or endocrine cell carcinoma may lie on the intermediate state between carcinoma and carcinoid tumor.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Carcinoid Tumor; Endorphins; Female; Gastrins; Gastrointestinal Hormones; Glucagon; Histocytochemistry; Humans; Male; Microscopy, Electron; Middle Aged; Motilin; Proglucagon; Protein Precursors; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide; Vasopressins

Topics: Adenocarcinoma, Mucinous; Adolescent; Adult; Child; Female; Gastrins; Histocytochemistry; Humans; Immunoenzyme Techniques; Microscopy, Electron; Ovarian Neoplasms; Serotonin; Silver; Somatostatin; Staining and Labeling

One of five gastro-entero-pancreatic hormones, gastrin, serotonin, histamine, glucagon, and insulin, was intraperitoneally administered for a long period to the rats that received N-methy-N'-nitro-N-nitrosoguanidine. A frequent development of scirrhous carcinoma was demonstrated in the group treated with gastrin.

Topics: Adenocarcinoma, Mucinous; Adenocarcinoma, Scirrhous; Animals; Gastrins; Glucagon; Histamine; Insulin; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Nitrosoguanidines; Pancreatic Hormones; Rats; Serotonin; Stomach; Stomach Neoplasms