Adenoma ; metabolism ; Adrenal Cortex Neoplasms ; metabolism ; Biomarkers, Tumor ; metabolism ; Calcium-Binding Proteins ; metabolism ; Carcinoma, Neuroendocrine ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Neuroendocrine Cells ; metabolism ; Neuroendocrine Tumors ; metabolism ; Secretagogins ; Small Cell Lung Carcinoma ; metabolism

Animals ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; physiopathology ; Carcinoma, Small Cell ; metabolism ; pathology ; physiopathology ; Cell Differentiation ; Chromogranin A ; metabolism ; Humans ; Male ; Neuroendocrine Cells ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; physiopathology

Here we report the detection and distribution of synaptophysin (SPY), non-neuronal enolase (NNE), glial fibrillary acidic protein (GFAP), vimentin (VIM), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) expression in the goat forestomach during prenatal development. A total of 140 embryos and fetuses were examined to evaluate protein expression from the first stage of prenatal life until birth. In all cases, SPY immunoreactivity was detected at 53 days gestation in the lamina propria-submucosa, tunica muscularis, serosa, and myenteric plexuses. Immunoreactivity to NNE was observed at 64 days gestation in the same locations as well as the epithelial layer. Glial cells were found at 64 days as indicated by signals corresponding to GFAP and VIM at 39 days. Positive staining for NPY and VIP was observed at 113, 75, and 95 days in the rumen, reticulum, and omasum, respectively, in the lamina propria-submucosa, tunica muscularis, and myenteric plexuses of each of these gastric compartments. These findings indicate possible preparation of the fetal goat forestomach for postnatal function. Compared to other ruminant species, neuroendocrine cells, glial cells and peptidergic innervations markers were detected earlier compared to sheep but at around the same stage as in deer.
Animals ; Biological Markers/metabolism ; Embryo, Mammalian ; Endocrine Cells/*metabolism ; Fetus/metabolism ; Gene Expression Regulation, Developmental ; Goats/*embryology/genetics ; Immunohistochemistry ; Neuroendocrine Cells/*metabolism ; Neuroglia/*metabolism ; Proteins/genetics ; Rumen/*embryology/metabolism

Breast Neoplasms, Male ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; surgery ; Carcinoma, Papillary ; metabolism ; pathology ; surgery ; Cell Differentiation ; Chromogranin A ; metabolism ; Humans ; Male ; Middle Aged ; Neuroendocrine Cells ; pathology ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Synaptophysin ; metabolism

OBJECTIVETo identify the differentially expressed proteins or peptides and potential biomarkers of tumorigenesis for colorectal cancers.

METHODSImmobilized pH gradient two-dimensional gel electrophoresis (2-DE) was used to separate and obtain the differentially expressed protein spots between colorectal cancers and matched normal mucosa. Liquid chromatography/mass spectrometry (LC-MS/MS) was used to characterize these proteins. Selected candidate proteins were further studied by Western blot, semi-quantitative RT-PCR and immunohistochemical staining.

RESULTSThirty-five protein spots showed marked expression changes (more than 5-fold) in colorectal carcinoma compared to normal mucosa. Fifteen proteins were up regulated and 20 were down regulated. Fourteen of these proteins were identified by tandem mass spectrometry, among which secretagogin (SCGN) was down-regulated and glucose-related protein (GRP) 78 was up-regulated in the tumors. The SCGN down-regulation was further supported by Western blot and RT-PCR analyses. Immunohistochemistry revealed that SCGN was strongly expressed in neuroendocrine cells of the colonic crypts and 53 of 54 (98%) neuroendocrine tumors. At protein level, although GRP78 was up regulated in colorectal carcinoma, there was no difference in the mRNA expression level between the tumor and paired normal mucosa.

CONCLUSIONSThe 2-DE combined with MS is a powerful tool for screening potential tumor biomarkers. The differentially expressed candidate proteins identified by 2-DE may be of significance in understanding the tumorigenesis of the colon cancer. SCGN is a potential biomarker for neuroendocrinal differentiation. GRP78 up-regulation in colorectal carcinomas may be related to its post-translational modification.

Biomarkers, Tumor ; genetics ; metabolism ; Calcium-Binding Proteins ; genetics ; metabolism ; Colorectal Neoplasms ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression Profiling ; methods ; Gene Expression Regulation, Neoplastic ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Molecular Chaperones ; genetics ; metabolism ; Neuroendocrine Cells ; metabolism ; Neuroendocrine Tumors ; metabolism ; Proteomics ; methods ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Secretagogins

OBJECTIVETo study the clinical and pathological features of pulmonary neuroendocrine cell hyperplasia and tumorlets with bronchiectasis.

METHODSBoth the clinicopathologic changes and immunohistochemical findings were examined with microscopy and EnVision method in 22 cases of pulmonary neuroendocrine cell hyperplasia and tumorlets.

RESULTSThe average age of the 22 patients was 53 years, with a male to female ratio of 9:13. On macroscopic examination the lungs showed bronchiectasis; one case was accompanied by gray-white, soft nodules (diameter < 5 mm). Microscopy of the HE sections showed the basic pathologic change was bronchiectasis, accompanied by neuroendocrine cell hyperplasia and tumorlet formation in the pulmonary parenchyma surrounding the bronchioles, presenting as single nodule (10 patients), or multifocal nodules (12 patients), with average size of 1.6 mm in diameter. No tumor cells were identified in the lymph nodes. Sixteen of 22 patients were disease-free after an average follow-up period of 58 months (17 - 117 months); one patient died suddenly after surgery; and five were loss of follow up. Immunohistologically, the tumor cells were positive for CgA (18/18), Syn (16/16), AE1/AE3 (16/16) , TTF-1 (14/15), and CD56 (14/14), and Ki-67 index was < 2% in 12 cases.

CONCLUSIONSImmunohistological staining for CgA, Syn, CD56, TTF-1 and AE1/AE3 can confirm the diagnosis. Early detection, pulmonary resection and follow-up help prevent the progression of these diseases.

Adult ; Aged ; Bronchiectasis ; pathology ; Chromogranin A ; metabolism ; DNA-Binding Proteins ; metabolism ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Hyperplasia ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neuroendocrine Cells ; pathology ; Neuroendocrine Tumors ; metabolism ; pathology ; surgery ; Pneumonectomy ; Synaptophysin ; metabolism ; Transcription Factors

OBJECTIVETo investigate neuroendocrine differentiation and its mechanism in ovarian epithelial tumors.

METHODSNeuroendocrine (NE) cells were identified by immunohistochemical staining for chromogranin A and synaptophysin in 79 cases of ovarian epithelial tumor and 22 cases of normal ovary. Double-labeling technique was used for simultaneous detection of CgA and epithelial membrane antigean (EMA), and the staining intensity was quantitatively evaluated using an image analysis system.

RESULTSThe positive staining rate for CgA and SYN in ovarian epithelial tumors was 59.4% and 65.36%, respectively, which was higher than that in normal ovary (P=0.000), in which numerous NE cells were found. Both the number and staining intensity of NE cells in ovarian epithelial tumor were increased as compared with normal ovary. Cells co-expressing CgA and EMA were detected in the ovarian epithelial tumors.

CONCLUSIONThe presence of NE cells in ovarian epithelial tumor suggests heterogeneity of the tumors, and the occurrence of "multidirectional differentiation cells" within the these tumors indicates that NE cells might derive from malignant cells with multidirectional differentiation capacity.

Adult ; Aged ; Case-Control Studies ; Cell Differentiation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasms, Glandular and Epithelial ; genetics ; metabolism ; pathology ; Neuroendocrine Cells ; metabolism ; pathology ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Ovary ; cytology ; metabolism ; pathology ; Young Adult

Nesidioblastosis is a term used to describe pathologic overgrowth of pancreatic islet cells. It also means maldistribution of islet cells within the ductules of exocrine pancreas. Generally, nesidioblastosis occurs in beta-cell and causes neonatal hyperinsulinemic hypoglycemia or adult noninsulinoma pancreatogenous hypoglycemia syndrome. Alpha-cell nesidioblastosis and hyperplasia is an extremely rare disorder. It often accompanies glucagon-producing marco- and mircoadenoma without typical glucagonoma syndrome. A 35-year-old female was referred to our hospital with recurrent acute pancreatitis. On radiologic studies, 1.5 cm sized mass was noted in pancreas tail. Cytological evaluation with EUS-fine-needle aspiration suggested serous cystadenoma. She received distal pancreatectomy. The histologic examination revealed a 1.7 cm sized neuroendocrine tumor positive for immunohistochemical staining with glucagon antibody. Multiple glucagon-producing micro endocrine cell tumors were scattered next to the main tumor. Additionally, diffuse hyperplasia of pancreatic islets and ectopic proliferation of islet cells in centroacinar area, findings compatible to nesidioblastosis, were seen. These hyperplasia and almost all nesidioblastic cells were positive for glucagon immunochemistry. Even though serum glucagon level still remained higher than the reference value, she has been followed-up without any evidence of recurrence or hormone related symptoms. Herein, we report a case of alpha-cell nesidioblastosis and hyperplasia combined with glucagon-producing neuroendocrine tumor with literature review.
Adult ; Chromogranin A/blood ; Female ; Glucagon/*metabolism ; Glucagon-Secreting Cells/metabolism ; Humans ; Hyperplasia/complications/*diagnosis ; Islets of Langerhans/metabolism/ultrasonography ; Nesidioblastosis/complications/*diagnosis ; Neuroendocrine Tumors/complications/*diagnosis/pathology ; Pancreas/*pathology ; Tomography, X-Ray Computed

Autoimmune Diseases ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Female ; Gastrectomy ; Gastric Mucosa ; pathology ; Gastrin-Secreting Cells ; metabolism ; pathology ; Gastrins ; metabolism ; Gastritis, Atrophic ; metabolism ; pathology ; surgery ; Humans ; Hyperplasia ; Middle Aged ; Mucin-6 ; metabolism ; Neuroendocrine Tumors ; metabolism ; pathology ; surgery ; Stomach ; pathology ; surgery ; Stomach Neoplasms ; metabolism ; pathology ; surgery ; Synaptophysin ; metabolism

OBJECTIVETo study the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades.

METHODSThe clinicopathologic features of 139 cases of neuroendocrine neoplasm occurring in digestive system were retrospectively reviewed and graded according to the 2010 World Health Organization classification of tumours of the digestive system. Immunohistochemical study for synaptophysin, chromogranin A and Ki-67 was carried out. The follow-up and survival data were analysed using Kaplan-Meier method. Prognostic factors were tested by Log-rank testing and independent risk factors were analysed using Cox regression model.

RESULTSAmongst the 139 cases studied, there were 88 cases (63.3%) of grade 1 tumors, 9 cases (6.5%) of grade 2 tumors and 42 cases (30.2%) of grade 3 tumors. There was diffusely positive staining for synaptophysin and chromogranin A in most of the grade 1 and grade 2 tumors. The staining in grade 3 tumors however was focal (P < 0.05). The differences in tumor size, depth of invasion, presence of tumor emboli, perineural permeation, nodal involvement, distant metastasis and survival rate amongst the three groups was statistically significant (P < 0.05).

CONCLUSIONSThere is significant difference in the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. It is considered as an independent prognostic factor and represents a useful tool for prognostic evaluation of such tumors, both in clinical practice and research.

Adult ; Aged ; Aged, 80 and over ; Chromogranin A ; metabolism ; Digestive System Neoplasms ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Neuroendocrine Tumors ; metabolism ; pathology ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Synaptophysin ; metabolism ; Tumor Burden ; Young Adult