Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have attempted to characterize a group of bronchopulmonary neoplasms that share certain structural features with true carcinoids but appear distinctly more pleomorphic and behave far more aggressively. In reviewing our files from 1973 to 1982, 11 such neoplasms were identified; the original diagnoses were "atypical bronchial carcinoid" (3 cases), "malignant carcinoid" (1 case), "bronchial carcinoid" (3 cases), "peripheral carcinoid" (2 cases), and "peripheral oat cell carcinoma" (2 cases). Of the 11 neoplasms, 5 were central and 6 were peripherally located. At presentation, 7 patients had lymph node metastases and 1 had a distant metastasis. No patient had a conventionally defined hormonal syndrome; however, 2 patients had a history of episodic flushing, one of which was associated with diarrhea. All cases were studied by light microscopy and light microscopic immunohistochemistry for NSE (neuron-specific enolase), serotonin, and broad-spectrum neuropeptides. Five cases were studied by electron microscopy. By light microscopy, the tumors were composed of solid clusters of polygonal to fusiform cells in an evident organoid arrangement. Foci of glandular and/or squamous differentiation were seen in 7 cases. Pleomorphism was moderate and mitoses were readily found. Focal necrosis was seen. By immunohistochemistry, 10 cases expressed NSE immunoreactivity. All cases demonstrated hormonal immunoreactivity; in 9 cases, immunoreactivity for more than one hormone was observed. The hormones most frequently expressed were serotonin, bombesin, gastrin, leu-enkephalin, and ACTH. By electron microscopy, all cases studied contained heterogeneous populations of neurosecretory granules; the latter, however, were not abundant and tended to aggregate either in the basal pole of the cells or, more frequently, interlacing "dendritelike" cytoplasmic processes. Aggregates of intermediate filaments were frequently seen. Basal lamina deposition was seen but gaps and larger areas of discontinuity were frequent. We believe that these neoplasms constitute a distinct pathologic entity for which the term "well-differentiated neuroendocrine carcinoma" has been proposed. Clinically, these tumors merit special attention since they are demonstrably more aggressive than true carcinoids but are distinctly less malignant than the intermediate or small cell variants of neuroendocrine carcinoma.
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PMID:Immunohistochemical and ultrastructural analysis of bronchopulmonary neuroendocrine neoplasms. II. Well-differentiated neuroendocrine carcinomas. 608 31

Twenty-five strictly defined bronchopulmonary carcinoids were studied by light microscopic immunohistochemistry by the peroxidase technique for NSE (neuron-specific enolase), serotonin, and a broad spectrum of neuropeptides. Eighteen cases were also studied by electron microscopy. Twenty-three of the twenty-five cases showed immunostaining for NSE; 24 cases displayed immunostaining for at least two of the hormones tested for; the single case that failed to show hormonal immuno-reactivity was however positive for NSE and had granules by electron microscopy. Serotonin was the most frequently demonstrated hormone followed by bombesin, vasoactive intestinal peptide, gastrin, leu-enkephalin , alpha-melanocyte stimulating hormone, somatostatin, substance P, and calcitonin. In several cases, adjacent-step sections stained for different hormones strongly indicated immunoreactivity for more than one hormone in single neoplastic cells. By electron microscopy, all 18 cases studied showed generally abundant neurosecretory granules, which, however, displayed considerable heterogeneity in their size, shape, and density. Twelve of these eighteen cases displayed evidence of squamous differentiation and 10 showed characteristic exocrine lumina. The capability of single neuroendocrine tumors and single neuroendocrine tumor cells to produce more than one immunoreactive hormone is hereby amply confirmed; these broad capabilities are certainly reflected in the heterogeneous granule populations seen by electron microscopy. The synchronous presence of squamous and exocrine features in broncho-pulmonary carcinoids indicates that they too are capable of multidirectional differentiation, which should not detract from their being regarded basically as well-differentiated neuroendocrine neoplasms. The clinical significance of strictly defining bronchial carcinoids is underscored by the fact that of 25 cases followed for 2-13 years, only one developed metastases 9 years postoperatively.
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PMID:Immunohistochemical and ultrastructural analysis of bronchopulmonary neuroendocrine neoplasms. I. Carcinoids. 637 57

Macroscopic stomach tumors induced in Sprague-Dawley rats during two chronic bioassays with the acetanilide herbicide butachlor at a dietary concentration of 3000 ppm, were evaluated histologically and immunohistochemically in order to determine their identity and pathogenesis. The tumors, which occurred primarily in female rats, were a heterogeneous series, including a few consisting wholly or partly of classic solid or anaplastic epithelium, but with the majority containing diffusely distributed primitive neoplastic cells. The latter had either the general appearance of undifferentiated epithelium or presented a more "mesenchyme-like" pattern where the cells were epithelioid, blastema-like, neuroendocrine-like or sarcoma-like with fascicular disposition. Gastric glandular profiles were also present, usually located near the periphery of the tumors, but in some cases extending into the diffuse tumor tissue. Most of the tumors displayed variable immunohistochemical reactivity for cytokeratin, vimentin and neuron-specific enolase but were negative for muscle-specific actin or desmin except in the stromal tracts. Detailed examination of all available gastric tissue revealed the presence of additional microscopic neoplasms and precursor hyperplastic lesions. All of these were typical gastric neuroendocrine cell lesions (gastric carcinoids) originating in the fundic mucosa but occasionally invading submucosally, and consisting of epithelial cells in organized clusters, rosettes or primitive tubules. The enterochromaffin-like (ECL) nature of these microscopic neoplasms and precursor lesions was substantiated by strong immunohistochemical reactivity for cytokeratin, neuron-specific enolase and chromogranin A, and a negative reaction for vimentin. One microscopic tumor showed a transition from differentiated neuroendocrine type in the fundic mucosa to a dispersed "mesenchyme-like" pattern in the submucosal extension. An additional finding in the butachlor-treated male and female rats was atrophy of the fundic mucosa involving, in particular, reduction in the numbers of parietal cells. This effect was dose-related, being most severe in the high-dose (3000 ppm) females. On the basis of their morphological characteristics, coupled with the continuity evident in the microscopic lesions, it is concluded that the macroscopic stomach tumors associated with the dietary administration of butachlor are poorly differentiated gastric carcinoids, in some cases admixed with a non-neuroendocrine epithelial element. Fundic ECL and stem cells are known to be under the trophic influence of gastrin, which is apparently responsible for the induction of the tumors associated with butachlor administration. Gastric tumor development involving gastrin is recognized as a secondary, hormonal mechanism of carcinogenesis, demonstrating a dose-threshold phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identity and pathogenesis of stomach tumors in Sprague-Dawley rats associated with the dietary administration of butachlor. 758 Jan 13

We present the cytologic, immunohistochemical, flow cytometric and ultrastructural findings of a case of invasive ductal carcinoma of the breast with features of neuroendocrine differentiation occurring in an 83-year-old male. Fine needle aspiration (FNA) cytology of the patient's tumor demonstrated a markedly cellular specimen to discohesive tumor cells, present primarily singly, with occasional loose groups. The cells were relatively large, with pleomorphic, eccentrically placed, round to oval nuclei. The cytoplasm was abundant and contained prominent red granules (Papanicolaou stain) that were also argyrophilic. Immunohistochemical studies performed on the aspirate and the subsequently excised malignant breast tissue revealed positive staining for neuron-specific enolase, chromogranin A, synaptophysin and gastrin. Also, the majority of the tumor stained positive with antibodies to both estrogen and progesterone hormone receptors. DNA flow cytometry demonstrated an aneuploid stemline population with a DNA index of 1.73 and an S-phase fraction of 4.5%. Electron microscopy was performed on the FNA material, and numerous variable-sized, membrane-bound, dense-core granules diffusely scattered within the cytoplasm of the neoplastic cells were identified. The specific cytologic features of this tumor, along with the immunocytochemical and ultrastructural features, can aid the pathologist in rendering an accurate FNA diagnosis of this specific subtype of breast carcinoma.
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PMID:Fine needle aspiration cytology of a male breast carcinoma exhibiting neuroendocrine differentiation. Report of a case with immunohistochemical, flow cytometric and ultrastructural analysis. 763 60

The cases of three patients with primary carcinoid tumor of the testis were reported. The patients were 41, 44, and 83 years of age. At initial examination, all three had testicular masses with or without associated pain, and none had the carcinoid syndrome. The tumors measured 4.3 cm, 3.0 cm, and 6.5 cm in dimension. All three tumors manifested classic histologic features of carcinoid tumors. The neoplastic cells exhibited argyrophilia, and all were immunoreactive to chromogranin, serotonin, neuron-specific enolase, and cytokeratin. Two tumors had positive test results for gastrin and one had positive test results for substance P and vasoactive intestinal polypeptide. No tumors reacted with somatostatin, insulin, pancreatic polypeptide, or placental alkaline phosphatase. Intracytoplasmic, membrane-bound, round-to-elliptical pleomorphic granules were identified by ultrastructural analysis in all cases. DNA flow cytometric analysis revealed a low degree (near-diploid) DNA aneuploidy in all cases, with a DNA index of 1.15 in two tumors and 1.3 in the third tumor. The three patients are alive and well 11 years, 7 years, and 6 months, respectively, after diagnosis. A total of 57 cases of this entity, including the 3 reported here, have been reported. Of these, 43 were pure carcinoid, and 14 were associated with teratoma; 6 (11.6%) patients developed metastases. Tumor size and the presence of carcinoid syndrome have been found to correlate with metastatic potential. Neither tumor necrosis nor local tumor invasion (into vessels, tunica albuginea, etc.) correlated with adverse prognosis. Carcinoid tumor of the testis is a rare indolent neoplasm with potential for distant metastases.
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PMID:Primary carcinoid tumor of testis. Immunohistochemical, ultrastructural, and DNA flow cytometric study of three cases with a review of the literature. 768 60

Histologically normal liver biopsy specimens from patients with Hodgkin's lymphoma were investigated with three immunohistochemical methods for the occurrence of peptidergic nerve fibers and endocrine cells. Numerous immunoreactive nerve fibers were seen with antisera against peripheral nerves markers (neuron-specific enolase, neurofilament protein, and S-100). These nerve fibers were localized in the tunica media of branches of both the hepatic artery and portal vein, around the bile ducts, and in the connective tissue of the interlobular septa. In the liver, 10 types of peptidergic nerve fibers were detected: glucagon-, glucagon-like peptide- (GLP), somatostatin-, neuropeptide Y- (NPY), vasoactive intestinal polypeptide-, neurotensin-, gastrin/cholecystokinin C-terminus-, substance P-, serotonin-, and galanin-immunoreactive nerve fibers. GLP-, somatostatin-, NPY-, neurotensin-, substance P-, and galanin-immunoreactive nerve fibers were abundant; the other nerve fibers were scarce. The nerve fibers showed two distinct patterns of distribution: they occurred in the blood vessel wall and in connective tissue of the interlobular septum. Pancreatic polypeptide- and NPY-immunoreactive cells were found among the lining epithelial cells of the bile ducts in the interlobular septum.
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PMID:Peptidergic innervation and endocrine cells in the human liver. 769 56

The studies were performed on pig embryos between 23rd and 31st day of intrauterine life. Immunocytochemical markers of neuroendocrine cells, i.e. neuron-specific enolase, chromogranin and synaptophysin as well as basal hormones, i.e. insulin, glucagon, somatostatin, pancreatic polypeptide and, additionally, serotonin and gastrin were detected in serial sections. Our studies indicate that differentiation of pancreatic endocrine cells does not take place unitemporally. At the first stage, the cells acquire the traits of neuroendocrine cells and secrete more than one hormone while final specialization toward cells secreting individual hormones take places at a later stage.
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PMID:Immunocytochemical studies on pancreatic endocrine cells at early stages of development of the pig. 784 63

Previously, we have shown that a significant proportion of human gastric carcinomas of the diffuse type may be neuroendocrine tumors derived from the enterochromaffinlike (ECL) cell. The growth of the ECL cell is specifically regulated by gastrin, suggesting an important role of gastrin in human gastric carcinogenesis. However, patients with antral-resected stomachs have reduced plasma gastrin and despite that an increased risk of gastric cancer. Recently, it has been shown that gastrin has a negative trophic effect on the oxyntic D-cell of the rat. The present study evaluates whether gastric stump carcinomas are D-cell derived. Twenty gastric stump carcinomas that had developed from 20 to 53 years after antral resection were examined for neuroendocrine differentiation by neuron-specific enolase immunohistochemistry and for D-cell origin by somatostatin immunohistochemistry. Half the tumors were classified as gastric carcinomas of the intestinal type, while the other half initially was classified as gastric carcinomas of the diffuse type. One of these latter tumors could, however, be reclassified as carcinoid tumor by appearance in hematoxylin erythrosin saffron-stained sections as well as by neuron-specific enolase positivity. Interestingly, this tumor was also positive for somatostatin, suggesting D-cell origin. Three other tumors were positive for neuron-specific enolase, but they were negative for somatostatin. Nevertheless, this study suggests that some gastric stump carcinomas may be malignant neuroendocrine tumors derived from neuroendocrine cells and possibly from D-cells. Furthermore, this study may indicate an important role for hormones and neuroendocrine cells in human gastric carcinogenesis.
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PMID:Do neuroendocrine cells, particularly the D-cell, play a role in the development of gastric stump cancer? 786 15

31 cases of the so-called sclerosing hemangiomas of the lung were studied by light microscope, immunohistochemical and electron microscopy. This tumor is benign and has 3 histologic patterns: papillary, hemangioma-like and solid type. Characteristic morphology being uniform round tumor cells, lying within the stroma in different patterns and regarded as the major component of sclerosing hemangioma, expressing neuroendocrine markers which include chromagranin A, neuron-specific enolase, ACTH, growth hormone, calcitonin and gastrin. Only a few tumor cells were positive for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), all the tumor cells were negative for keratin (Polyclonal, Z622) stain. However, in contrast to the round tumor cells, the cells lining papillary projections or cystic spaces, which presented as normal or hyperplastic alveolar cells, stained positive for keratin, EMA and CEA but negative for neuroendocrine markers. Both the surface cells and tumor cells were negative for Factor VIII-related antigen and alpha 1-AT. Therefore, pulmonary sclerosing hemangioma was regarded to be a benign tumor originating from the neuroendocrine cells of the lung and we suggest that it be renamed as benign neuroendocrine tumor of the lung (LBNET). This viewpoint has not been previously reported in the literature.
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PMID:[A benign neuroendocrine tumor of the lung: study on the origin of the so-called sclerosing hemangioma of the lung]. 808 41

Two cases of paraganglioma of the urinary bladder are reported. Their immunohistochemical profiles and the clinical features are compared with other cases in the literature. The three pan-endocrine markers (neuron-specific enolase, synaptophysin and chromogrannin) were positive in both cases. Positivity to other neuropeptides (including the present two cases and those in literature) includes adrenocorticotropic hormone (three out of five cases), calcitonin (two out of nine cases), gastrin (two out of six cases), glial fibrillary acidic protein (one out of five cases), glucagon (two out of six cases), serotonin (five out of nine cases), and somatostatin (four out of eight cases). A previously unmentioned association between paraganglioma of the urinary bladder and carcinoid in the gastrointestinal tract is noted in one of the present cases. This peculiar association highlights the importance of multiplicity of tumours of the neuroendocrine system other than the classical multiple endocrine neoplasia syndromes.
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PMID:Paraganglioma of the urinary bladder: an immunohistochemical study and report of an unusual association with intestinal carcinoid. 810 19


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