RNA interference of achaete-scute homolog 1 in mouse prostate neuroendocrine cells reveals its gene targets and DNA binding sites. (49/327)

We have previously characterized a transgenic mouse model (CR2-TAg) of metastatic prostate cancer arising in the neuroendocrine (NE) cell lineage. Biomarkers of NE differentiation in this model are expressed in conventional adenocarcinoma of the prostate with NE features. To further characterize the pathways that control NE proliferation, differentiation, and survival, we established prostate NE cancer (PNEC) cell lines from CR2-TAg prostate tumors and metastases. GeneChip analyses of cell lines harvested at different passages, and as xenografted tumors, indicated that PNECs express consistent features ex vivo and in vivo and share a remarkable degree of similarity with primary CR2-TAg prostate NE tumors. PNECs express mAsh1, a basic helix-loop-helix (bHLH) transcription factor essential for NE cell differentiation in other tissues. RNA interference knockdown of mAsh1, GeneChip comparisons of treated and control cell populations, and a computational analysis of down-regulated genes identified 12 transcriptional motifs enriched in the gene set. Affected genes, including Adcy9, Hes6, Iapp1, Ndrg4, c-Myb, and Mesdc2, are enriched for a palindromic E-box motif, CAGCTG, indicating that it is a physiologically relevant mAsh1 binding site. The enrichment of a c-Myb binding site and the finding that c-Myb is down-regulated by mAsh1 RNA interference suggest that mAsh1 and c-Myb are in the same signaling pathway. Our data indicate that mAsh1 negatively regulates the cell cycle (e.g., via enhanced Cdkn2d, Bub1 expression), promotes differentiation (e.g., through effects on cAMP), and enhances survival by inhibiting apoptosis. PNEC cell lines should be generally useful for genetic and/or pharmacologic studies of the regulation of NE cell proliferation, differentiation, and tumorigenesis.  (+info)

Thyroid transcription factor-1, but not p53, is helpful in distinguishing moderately differentiated neuroendocrine carcinoma of the larynx from medullary carcinoma of the thyroid. (50/327)

Moderately differentiated neuroendocrine carcinoma/atypical carcinoid tumor is the most common nonsquamous malignancy in the larynx; however, due to morphologic overlap and calcitonin immunoreactivity, it can be difficult to distinguish from thyroid medullary carcinoma. Currently, low serum calcitonin is the most reliable means for distinguishing primary laryngeal moderately differentiated neuroendocrine carcinoma from metastatic medullary carcinoma. Thyroid transcription factor-1 (TTF-1) is positive in at least 80% of medullary carcinomas, but has not been evaluated in laryngeal moderately differentiated neuroendocrine carcinomas. Additionally, it has been suggested that p53 is positive in laryngeal moderately differentiated neuroendocrine carcinomas and negative in other neuroendocrine tumors, but this has not been validated. The purpose of this study was to determine if the immunohistochemical markers TTF-1 and p53 could be used to discriminate between laryngeal moderately differentiated neuroendocrine carcinomas and thyroid medullary carcinomas. Eight laryngeal moderately differentiated neuroendocrine carcinomas and 10 thyroid medullary carcinomas were identified from the archival files of the BWH and MGH Pathology Departments. Hematoxylin and eosin slides were reviewed, and immunohistochemistry was performed using antibodies to calcitonin, TTF-1, and p53. Calcitonin immunohistochemistry demonstrated immunoreactivity in 100% of laryngeal moderately differentiated neuroendocrine carcinomas (N=8) and 100% of thyroid medullary carcinomas (N=10). There was weak, focal immunoreactivity with TTF-1 in one of eight (13%) laryngeal moderately differentiated neuroendocrine carcinomas, whereas nine of ten (90%) medullary carcinomas were positive for TTF-1, with strong diffuse staining in seven of these cases (78%). p53 was positive in three of six (50%) laryngeal moderately differentiated neuroendocrine carcinomas, and three of ten (30%) medullary carcinomas. Our data demonstrate that immunoreactivity for TTF-1, but not calcitonin or p53, may be helpful in distinguishing laryngeal moderately differentiated neuroendocrine carcinoma and thyroid medullary carcinoma. In particular, diffuse and/or strong TTF-1 immunoreactivity favors a diagnosis of primary thyroid medullary carcinoma over laryngeal moderately differentiated neuroendocrine carcinoma.  (+info)

Multiple neuroendocrine tumors of the pancreas associated with pancreas divisum. (51/327)

Pancreas divisum is the most common congenital anomaly of the pancreas, characterized by missing fusion of the ventral and dorsal pancreatic duct. It may cause pancreatitis, but is rarely associated with malignancy.We report herein for the first time the rare association, in a symptomless patient, of multiple neuroendocrine tumors of the pancreas with pancreas divisum and a failure of the exocrine system. Diagnosis was made incidentally by routine abdominal ultrasound. Laboratory examinations and a fine-needle aspiration revealed the neuroendocrine nature of the tumor. Spleen-preserving left pancreas resection was performed, with evidence of multiple neuroendocrine tumors of the pancreas with the typical histological characteristics. Eighteen months later the patient is still free of tumor burden.  (+info)

Role of curved planar reformations using multidetector spiral CT in diagnosis of pancreatic and peripancreatic diseases. (52/327)

AIM: To investigate the role of curved planar reformations using multidetector spiral CT (MSCT) in diagnosis of pancreatic and peripancreatic diseases. METHODS: From October 2001 to September 2003, 47 consecutive patients with pancreatic or peripancreatic diseases, which were confirmed by operation, endoscopic retrograde cholangiopancreatography and clinical follow-up, were enrolled in this study. CT scanning was performed at a MSCT with four rows of detector. A set of images with an effective thickness of 1.0-2.0 mm and a gap of 0.5-1.0 mm (50% overlap) were acquired in all patients for post-processing. Curved planar reformations were carried out by drawing a curved line on transverse source images, coronal or sagittal multiplanar reformations according to certain anatomic structures (such as cholangiopancreatic ducts or peripancreatic vessels) and the position of lesion. RESULTS: With thin collimation, MSCT could acquire high-quality curved planar reformations to display the profile of the whole pancreas, to trace the cholangiopancreatic ducts and peripancreatic vessels, and to show the relationship of lesions with pancreas and peripancreatic anatomic structures in one curved plane, which facilitates diagnosis and rapid communication of diagnostic information with referring physicians. CONCLUSION: MSCT with thin collimation could be used to create high-quality curved planar reformations in evaluating pancreatic and peripancreatic diseases with pertinent anatomic information and relative pathologic signs to facilitate the diagnosis and enhance communication with the referring physician. Curved planar reformations can serve as supplements for transverse images in diagnosis and management of pancreatic and peripancreatic diseases.  (+info)

Breast cancer with neuroendocrine differentiation detected by unique staining pattern of neoplastic cells in hercep test. (53/327)

Hercep Test (DAKO) is an immunohistological screening kit to select cases of advanced breast cancer with indication for treatment with a humanized mouse monoclonal antibody to human epidermal growth factor receptor-2, trasthzumab (Herceptin). We report a case of an 84-year-old female with invasive ductal carcinoma of the right breast, whose neoplastic cells showed a unique staining pattern in Hercep Test. The cells showed an intracytoplasmic fine granular staining pattern, instead of the membranous pattern of typical breast cancer cells. This unique staining pattern suggested some special features of the neoplastic cells. This case was finally diagnosed as invasive ductal carcinoma with focal neuroendocrine differentiation by subsequent imunohistochemical and electron microscopic examinations. The neoplastic cells showed positive reactivity for grimelius stain, chromogranin A, synaptophysin, and neuronspecific enolase, as well as electron-dense neurosecretory granules (up to 150 nm in diameter). This unique staining pattern of the neoplastic cells with Hercep Test is a useful clue to detect breast cancer with neuroendocrine differentiation, which is likely to be missed in routine examination. Clinical and pathologic findings including immunohistochemical and ultrastructural findings of this case are reported, together with a brief review of the literature.  (+info)

Position of nuclear medicine techniques in the diagnostic work-up of neuroendocrine tumors. (54/327)

In recent years nuclear medicine has contributed to the impressive development of the knowledge of neuroendocrine tumors in terms of biology (receptor scintigraphy), pharmacology (development of new tracers), and therapy (radiometabolic therapy). At present, it is impossible to plan the management of a patient affected by a neuroendocrine tumor without performing nuclear medicine examinations. The contribution of nuclear medicine had affected and improved the management of these patients by offering various important options that are part of the modern diagnosis and treatment protocols. The clinical experience and the literature confirm that, among the wide variety of tracers and nuclear medicine modalities available today, metaiodobenzylguanidine (MIBG) and DTPA-D-Phe-octreotide (pentetreotide) are the radiopharmaceuticals of current clinical use. Several new somatostatin analogues are under investigation. Positron emission tomography (PET) supplies a range of labelled compounds to be used for the visualization of tumor biochemistry. In addition to the first routinely used PET tracer in oncology, 18F-labelled deoxyglucose (FDG), a number of radiopharmaceuticals based on different precursors such as fluorodopamine and 5-hydroxytryptophan (5-HTP) are going to gain a clinical role. Of course, the diagnosis of neuroendocrine tumors has to be based on integrated information derived from different examinations including nuclear medicine studies. The clinical presentation of neuroendocrine tumors is highly variable: sometimes they manifest typical or atypical symptoms but they may also be detected by chance during an X-ray or ultrasound examination carried out for other reasons. At disease presentation nuclear medicine modalities are sometimes able to direct physicians towards the clinical diagnosis thanks to the specificity of their imaging mechanisms. They also play a role in disease staging and restaging, patient follow-up and treatment monitoring. In addition, the biological characterisation of neuroendocrine tissues (receptor status, glucose metabolism, differentiation, etc.) allows the interpretation of radiopharmaceutical uptake as a prognostic parameter and sometimes as a predictor of the response to treatment.  (+info)

Daily cyclic changes in the urinary excretion of 5-hydroxyindoleacetic acid in patients with carcinoid tumors. (55/327)

BACKGROUND: Vasoactive peptides produced by neuroendocrine tumors can induce characteristic symptoms of the carcinoid syndrome (flushing, diarrhea, and wheezing). To what extent external factors provoke these symptoms and how excretion of 5-hydroxyindoleacetic acid (5-HIAA), the degradation product of serotonin, varies throughout the day remain unknown. In this study, we investigated whether symptoms and daily activity are related to 5-HIAA excretion and whether 24-h urine collection is needed. METHODS: In 26 patients with metastatic carcinoid (14 men and 12 women; median age, 60 years) urine was collected in portions of 4 or 8 h during 2 days. Patients were asked to keep a diary in which they noted symptoms of flushes, consistency of stools, activities, and food intake. RESULTS: Excretion of 5-HIAA in 24-h urine was increased in 88% of the patients (median, 515 micromol/24 h). Overnight-collected urine appeared the most representative for 24-h collection concentrations (correlation coefficient = 0.81). We found no clear correlation between symptoms of the carcinoid syndrome and degree of activity. Watery diarrhea was reported only by patients with strong variations in 5-HIAA excretion. One-half of the patients (n = 16) exhibited a high variability in urinary 5-HIAA excretion throughout the day, with increased concentrations most prominent in morning collections (P = 0.0074) and lower concentrations in the evening (P = 0.0034). In the other patients these curves were flat. CONCLUSIONS: Cyclic changes in patients relate to high variability in 5-HIAA excretion. Overnight-collected urine can replace the 24-h urine collection, and marked variations in 5-HIAA excretion seem to be associated with severity of diarrhea.  (+info)

An unusual presentation of "silent" disseminated pancreatic neuroendocrine tumor. (56/327)

To present a patient diagnosed with pancreatic carcinoid that was extremely rare and produced an atypical carcinoid syndrome. We reported a 58-year old male patient who presented with long standing, prominent cervical lymphadenopathy and occasional watery diarrhea. Pathohistological and immunohistochemical examination of lymph node biopsy showed a metastatic neuroendocrine tumor, which was histological type A of carcinoid (EMA+, cytokeratin+, CEA-, NSE+, chromogranin A+, synaptophysin+, insulin-). Bone marrow biopsy showed identical findings. Primary site of the tumor was pancreas and diagnosis was made according to cytological and immunocytochemical analysis of the tumor cells obtained with aspiration biopsy of pancreatic mass (12 mm in diameter) under endoscopic ultrasound guidance. However, serotonin levels in blood and urine samples were normal. It is difficulty to establish the precise diagnosis of a "functionally inactive" pancreatic carcinoid and aspiration biopsy of pancreatic tumor under endoscopic ultrasound guidance can be used as a new potent diagnostic tool.  (+info)