Although it is becoming widely accepted that medulloblastoma and cerebral primitive neuroectodermal tumor(PNET) are identical tumors occurring at different locations, there are some controversies in their orgin and pathological classification. As a method of investigating whether the tumors are identical in pathological aspects, immunohistochemical characteristics of medulloblastomas and cerebral PNETs were compared in this study. Also the prognostic significance of the immunohistochemical findings in medulloblastoma patients was analyzed. Clinical features of twenty-seven patients with medulloblastoma and eleven patients with cerebral PNET were reviewed, excluding tumors with significant cellular differentiation such as ependymoblastoma, pineoblastoma and neuroblastoma. The presence of glial fibrillary acidic protein(GFAP), neurofilament(NF), S-100 protein, vimentin, synaptophysin, and epithelial membrane antigen(EMA) was examined with immunohistochemical method and the differences of the results between the two tumors were statistically analyzed. The positive rates of NF and synaptophysin were significantly higher in medulloblastomas(p=0.006 and 0.003, respectively) and so was the positive rate of vimentin in cerebral PNET's(p=0.004). S-100 protein showed a higher positive rate in cerebral PNETs althought it was not statistically significant. Univariate and multivariate analyses did not show any significant correlation between the duration of survival and the presence of cellular antigens.
Classification ; Humans ; Immunohistochemistry ; Medulloblastoma ; Membranes ; Multivariate Analysis ; Neural Plate ; Neuroblastoma ; Neuroectodermal Tumors, Primitive* ; Pinealoma ; S100 Proteins ; Synaptophysin ; Vimentin

Caveolin-1 (Cav-1) is a marker protein for caveolae, and acts as scaffolding protein to regulate the activities of signaling molecules. Previous studies indicate that Cav-1 mainly locates at the base of axonal and dendritic terminals of mouse primary hippocampal neurons and plays an active role in the regulation of injury-induced synaptic and terminal remodeling in central nervous system. The aim of this study was to identify the expression profile of Cav-1 protein in the brains of rats at different ages and to investigate the role of Cav-1 in Y-maze bright-dark discrimination learning (BDL). Firstly, the expressions of Cav-1 in the brains of young (1-month), adult (3-month) and aged (22-month) rats were observed by Western blot. Higher expression in the hippocampus and lower expression in the cortex were shown in the adult rats. It was also found that the score of BDL was related with the expression level of Cav-1. Secondly, using open-field test for spontaneous locomotor activities (SLA) and BDL, the role of Cav-1 in the learning and memory was observed. Compared with that in the control adult group, the Cav-1 protein expression in the hippocampus and prefrontal cortex of Y-maze trained adult rats significantly increased, while no marked changes in the cerebellum. These results suggest that Cav-1 protein is involved in BDL and plays an important role in the plasticity of central nervous system.
Age Factors ; Animals ; Brain Chemistry ; Caveolin 1 ; analysis ; physiology ; Discrimination Learning ; GAP-43 Protein ; analysis ; Male ; Maze Learning ; Rats ; Rats, Sprague-Dawley ; Synaptophysin ; analysis

Patients with primary small cell carcinoma of the liver have rarely been described in medical literature. Knowledge of clinical, pathological and immunohistochemical properties remains limited. We described an 82-year-old female patient with primary small cell carcinoma of the liver. Histologically, the tumor showed typical morphology of a pulmonary small cell carcinoma. Immunohistochemically, the tumor revealed neuroendocrine differentiation; positive reaction for chromogranin, synaptophysin, CD56, and neuron specific enolase. The tumor was also positive for TTF-1 and c-kit but completely negative for hepatocyte, carcinoembryonic antigen, cytokeratin 7; 19; and 20. Herein, we discussed the clinical, pathological and immunohistochemical findings of extrapulmonary small cell carcinoma of the liver and reviewed the relevant literature.
Aged, 80 and over ; Antigens, CD56/analysis ; Carcinoma, Small Cell/metabolism/*pathology ; Chromogranins/analysis ; Female ; Humans ; Immunohistochemistry ; Liver/chemistry/*pathology ; Liver Neoplasms/metabolism/*pathology ; Lung Neoplasms/pathology ; Phosphopyruvate Hydratase/analysis ; Synaptophysin/analysis

OBJECTIVETo describe the morphologic features and immunohistochemistry of spindle cell carcinoma of breast with neuroendocrine differentiation.

METHODSRetrospective review of 2500 cases of breast carcinoma showed 5 cases (0.2%) with a predominance (> 80%) of spindle cell component. Amongst the 5 cases studied, 2 represented intraductal spindle cell carcinoma and 3 represented invasive spindle cell carcinoma. The paraffin sections were stained with hematoxylin and eosin, alcian blue, periodic acid-Schiff and reticulin stain. Immunohistochemical studies for AE1/AE3, CEA, EMA, CK7, 34betaE12, NSE, synaptophysin, chromogranin A, Leu-7, vimentin, S-100, SMA, calponin, estrogen receptor, progesterone receptor, c-erbB2, E-cadherin, Ki-67 and p53 were also carried out. Follow-up information was available in 4 of the 5 cases.

RESULTSThe mean age of the patients was 68 years. Histologically, all tumors were predominantly composed of elongated spindle cells. Three of these cases also contained tumor cells with vacuolated cytoplasm, alcian blue-positive tumor cells were observed in 4 cases. Immunohistochemically, the spindle tumor cells in all cases expressed AE1/AE3, CEA, EMA, E-cadherin and synaptophysin. CK7 was positive in 4 cases, NSE in 3 cases, chromogranin A and Leu-7 in 2 cases. Estrogen receptor was expressed in 4 cases and progesterone receptor in 2 cases. Overexpression of c-erbB2 oncoprotein was detected in only 1 case. Vimentin was focally positive in 1 case. Two cases of intraductal spindle cell carcinoma and 1 of the 3 cases of invasive spindle cell carcinoma were classified as neuroendocrine carcinoma of spindle cell type, while the remaining 2 cases of invasive spindle cell carcinoma were considered as metaplastic carcinoma with neuroendocrine differentiation. Amongst the 4 patients with follow-up information available, 3 were still alive 24 to 58 months after the initial diagnosis. One patient died within 27 months of diagnosis.

CONCLUSIONSThe presence of spindle tumor cells and sometimes intracytoplasmic mucin are useful morphologic clues in diagnosing spindle cell carcinoma of the breast with neuroendocrine differentiation. Intraductal neuroendocrine spindle cell carcinoma needs to be distinguished from usual ductal hyperplasia and intraductal papilloma. On the other hand, invasive spindle cell carcinoma with neuroendocrine differentiation needs to be distinguished from spindle cell myoepithelioma, malignant melanoma and sometimes soft tissue neoplasm.

Aged ; Biomarkers, Tumor ; analysis ; Breast Neoplasms ; chemistry ; pathology ; Carcinoma ; chemistry ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; chemistry ; pathology ; Chromogranin A ; Chromogranins ; analysis ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neuroendocrine Tumors ; chemistry ; pathology ; Phosphopyruvate Hydratase ; analysis ; Retrospective Studies ; Synaptophysin ; analysis

BACKGROUNDThere are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.

METHODSThe right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.

RESULTSGrafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded.

CONCLUSIONCultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

Animals ; Astrocytes ; transplantation ; Brain ; pathology ; Cell Proliferation ; Cell Survival ; Cells, Cultured ; Cerebral Infarction ; metabolism ; pathology ; therapy ; Fetal Tissue Transplantation ; Glial Fibrillary Acidic Protein ; analysis ; Humans ; Microtubule-Associated Proteins ; analysis ; Neocortex ; cytology ; Neurons ; transplantation ; Rats ; Synaptophysin ; analysis

BACKGROUND/AIMS: p53 is known to play a central role in sensing and signaling for the growth arrest and apoptosis in cells with DNA damage. Mutation of p53 is a frequent event in esophageal squamous cell carcinoma (ESCC). p16 protein binds to cyclin dependent kinase 4 (CDK4) inhibiting the ability of CDK4 to interact with cyclin D1, and stimulates the passage through the G1 phase of cell cycle. We observed the expression patterns and frequencies of p53, p16, and cyclin D1 in esophageal dysplasia and in esophageal squamous cell carcinomas. METHODS: In 15 patients of ESCC, 5 patients of esophageal dysplasia and 5 volunteers with normal esophagus, tissue specimens were taken from esophageal lesions during the operation or endoscopic examination. We used specific monoclonal antibodies for p53 protein, p16INK4 protein and cyclin D1. Immunoreactivity was scored. RESULTS: Mean age of all groups was 66 years old (range 47-93) and men to women ratio was 19:1. p53 mutation was observed in 87% (13/15) of ESCC, in 80% (4/5) of esophageal dysplasia, in 0% (0/5) of normal mucosa (p=0.001). p16 expression was seen in 40% (2/5) of esophageal dysplasia, 27% (4/15) of ESCC and 100% (5/5) of normal mucosa (p=0.016). Cyclin D1 expression was not significantly different among 20% (1/5) of esophageal dysplasia, 53% (8/15) of ESCC and 20% (1/5) of normal mucosa. Either the expression of p53 mutation or the loss of p16 occurred in 80% (4/5) of esophageal dysplasia and in 93% (14/15) of ESCC. CONCLUSIONS: The expression of p53 mutation and the loss of p16 might play a central role in the pathogenesis of esophageal squamous cell carcinoma (ESCC), and contribute to the development of precancerous lesion such as dysplasia. In addition, there is a possibility that the mutations of p53 and p16 silencing would be the early events in ESCC development.
Aged ; Carcinoma, Neuroendocrine/*diagnosis/pathology ; Chromogranin A/analysis/immunology ; Drainage ; Female ; Humans ; Immunohistochemistry ; Liver Abscess/*radiography/surgery ; Liver Neoplasms/*diagnosis/pathology ; Radiography, Abdominal ; Synaptophysin/analysis/immunology ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. METHODS: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. RESULTS: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512 patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n=2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. CONCLUSIONS: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy.
Adenocarcinoma/pathology ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; Carcinoma, Neuroendocrine/drug therapy/mortality/*pathology ; Chromogranin A/analysis/immunology ; Colorectal Neoplasms/drug therapy/mortality/*pathology ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Retrospective Studies ; Sigmoid Neoplasms/drug therapy/mortality/pathology ; Synaptophysin/analysis/immunology ; Tumor Markers, Biological/analysis/immunology

OBJECTIVETo study the pathologic characteristics and prognosis in different subtypes of adult medulloblastoma (MB).

METHODSThe clinical information, imaging findings and pathologic characteristics of 151 cases of adult medulloblastomas were retrospectively reviewed and analyzed by chi-square test. The survival data were assessed using the Kaplan-Meier method.

RESULTSAmongst the 151 MB cases studied, there were 73 cases of classic MB, 36 cases of desmoplastic/nodular MB, 39 cases of anaplastic MB and 3 cases of large cell MB. The primary tumors were more frequently located in cerebral hemisphere in desmoplastic/nodular MB than in other subtypes (P=0.000).On the other hand, large cell/anaplastic MB were associated with more frequently local recurrence and distant metastasis (P=0.003). The post-operative overall survival time ranged from 6 to 150 months, with median survival being (103.3±5.7) months (95%CI, 92.52 to 115.09). The median survival of classic MB, desmoplastic/nodular MB and large cell/anaplastic MB was (110.7±7.8) months, (125.5±7.6) months and (57.6±7.6) months, respectively. The differences were statistically significant (P=0.000).

CONCLUSIONSThe three variants of MB show different biologic behavior. Large cell/anaplastic MB represents an independent poor prognostic indicator in adults.

Adolescent ; Adult ; Cerebellar Neoplasms ; classification ; metabolism ; pathology ; radiotherapy ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen ; metabolism ; Male ; Medulloblastoma ; classification ; metabolism ; pathology ; radiotherapy ; surgery ; Middle Aged ; Neoplasm Recurrence, Local ; Phosphopyruvate Hydratase ; metabolism ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Synaptophysin ; metabolism ; Young Adult

OBJECTIVETo study the effects of ketamine combined with penehyclidine hydrochloride on the learning and memory abilities and the expression of synaptophysin in the hippocampus CA3 region in the brain of neonatal rats.

METHODSEighty seven-day-old Sprague-Dawly rats were randomly intraperitoneally injected with 50 mg/kg of ketamine (K group), 2 mg/kg of penehyclidine hydrochloride (P group), 50 mg/kg of ketamine plus 2 mg/kg penehyclidine hydrochloride (PK group) or normal saline (control group). The rats were trained and tested in a Morris water maze 14 days after administration. The immunhistochemical method was used to ascertain the expression of synaptophysin in the hippocampus CA3 region 24 hrs, 14 days and 28 days after administration.

RESULTSIn the Morris water maze training, the rats in the PK group performed worst, followed by the K group. The rats from the P and NS groups performed well. Compared with the NS group, the expression of synaptophysin in the K and the PK groups decreased significantly 24 hrs and 14 days after administration (p<0.05). The PK group had lower synaptophysin expression than the K group 24 hrs and 14 days after administration (p<0.05). Up to 28 days after administration, the synaptophysin expression increased in all of the four groups and there were no significant differences between groups.

CONCLUSIONSKetamine combined with penehyclidine hydrochloride may inhibit more significantly learning and memory abilities and the synaptophysin expression in the hippocampus CA3 region than ketamine alone in neonatal rats. Penehyclidine hydrochloride alone has no effect on learning and memory abilities and the synaptophysin expression. The synaptophysin expression may increase to a normal level by training and with increasing age.

Animals ; Animals, Newborn ; Cholinergic Antagonists ; pharmacology ; Drug Therapy, Combination ; Excitatory Amino Acid Antagonists ; pharmacology ; Hippocampus ; chemistry ; drug effects ; Ketamine ; pharmacology ; Maze Learning ; drug effects ; Memory ; drug effects ; Quinuclidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; physiology ; Synaptophysin ; analysis