Automated review - Keywords: nse.

Found 53 matching records.

90 neuroendocrine neoplasias (APUDomas) (including islet-cell tumours, phaeochromocytomas, medullary thyroid carcinomas, oat-cell tumours, and APUDomas of the gut, pancreas, and lungkeyword) reacted strongly with antisera to NSEkeyword. In addition, large amounts of the enzyme were found by radioimmunoassaykeyword in the tumours (mean 1626 +/- 479 SEM ng of NSEkeyword/mg protein), whereas control non-endocrine neoplasias contained less than 15 ng NSEkeyword/mg protein. Thus NSEkeyword, a specific enzyme produced in the neural and endocrine systems, was found to be produced in considerable quantities by all types of APUDomas but not in any non-endocrine tumours.
DAKO quick staining kits were used to immunostain for Epithelial Membrane Antigen (EMA) Neuron Specific Enolase (NSEkeyword) and S-100 protein (S-100) in 18 carcinoid tumors of the gastrointestinalkeyword tract. S-100 immunostainingkeyword showed immunopositive stellate cells present within the tumor especially within type A carcinoids. In addition in one carcinoid tumor thick, strongly S-100 positive bundles were noticed at the periphery of nests of tumor cells.
The light-microscopic and immunohistochemical characteristics of 65 duodenal carcinoids are presented. Most tumors showed a mixture of cribriform, insular, glandular, solid, and trabecular growth patterns. Eighty-five percent of the tumors were argyrophil and 15% argentaffin. The nonspecific neuroendocrine markers chromogranin, Leu-7, and neuron-specific enolase were positive in 97, 91, and 83% of tumors, respectively. Immunoreactivity for specific hormones/amines were as follows (percent positive tumors): somatostatin, 47%; N-gastrin, 56%; serotonin, 39%; calcitonin, 19%; insulin, 5%; pancreatickeyword polypeptide, 3%; adrenal corticotropic hormonekeyword, 0%; glucagon, 0%. Sixty-eight percent had gastrin/cholecystokinin-like reactivity. Ten psammomatous tumors were located near the ampulla; eight were somatostatin positive, including two in patients with neurofibromatosiskeyword. One additional tumor in a patient with neurofibromatosiskeyword lacked psammoma bodies but elaborated somatostatin. Eight additional tumors in nonneurofibromatosis patients produced solely somatostatin. Duodenal carcinoids often elaborate more than one polypeptide hormonekeyword; those in the ampulla often elaborate somatostatin and have psammoma bodies.
A case of thymic atypical carcinoidkeyword with Cushing's syndrome and unfavorable clinical course is reported. Immunohistochemical analysis reveals distinct staining of tumor cells for ACTH, neuron-specific enolase, chromogranins (CG) and S-100 protein and with PHE-5 monoclonal antibodykeyword. S-100-positive cells, which are present throughout the tumor, recall 'sustentacular cells', described in other neuroendocrine tumors.
In order to compare histologic subtypes and endocrine profiles, immunohistochemical and silver stains were performed on 120 appendiceal carcinoids. Forty-three were predominantly insular; 21 were mixed insular, glandular, and trabecular; 33 were goblet cell; 17 were tubular; and five were clear cell carcinoids. Many were cytokeratin-positive, but often focally. Goblet cell carcinoids contained few endocrine cells, but these were strongly argentaffin and positive for serotonin in nearly all, and positive for HPP in almost a third. All goblet cell and tubular carcinoids were diffusely positive for CEA and cytokeratin. Thus, among appendiceal carcinoids, the endocrine content varies according to histologic subtype.
About 50% of all insulin-producing insulomas are endowed with stromal amyloid deposits, which chemically are composed of a peptide designated islet amyloid polypeptide. This molecule has been observed by electron microscopical immunocytochemistry to occur exclusively in the beta-cells and is co-stored with insulin in the beta-cell granules.
Six pulmonary spindle cell carcinoids were reviewed. Immunoreactivity for chromogranin, neuron-specific enolase, synaptophysinkeyword, S-100 protein and Leu-7 was typically present; bombesin, serotonin, insulin and calcitonin were focally present in some cases. No reactivity for adrenocorticotropic hormonekeyword, somatostatin, gastrin, vasoactive intestinal polypeptide, pancreatickeyword polypeptide, low-molecular-weight cytokeratin (MAK-6) or carcinoembryonic antigen was observed.
A 54-year-old man underwent a radical nephrectomy for a presumed renal cell carcinomakeyword. The tumor cells were argentaffin- and argyrophil-negative but were chromogranin-, neuron-specific enolase-, and leu-7-positive.
Atypical carcinoidkeyword tumor of the lungkeyword with amyloid stroma seen in a 43-year-old woman is reported. Immunostainingkeyword for amylin, a polypeptide isolated from insular amyloid in type II diabetes mellituskeyword or insulinomakeyword showing a 50% homology with calcitonin gene-related peptide (CGRP), was negative. The specificity of immunostainingkeyword for calcitonin, CGRP and amylin was confirmed by immunoabsorption tests using synthetic humankeyword antigens. Immunoelectron microscopic studies disclosed peptide localization in neurosecretory-type granules and CGRP immunoreactivity in extracellular amyloid fibrils. This is the first report describing CGRP as a component of amyloid of endocrine origin.
Investigators have analyzed two lesions from bile ductkeyword adenomas,which in addition to the typical small caliber ducts, contained periductular nests and clusters of uniform round cells, suggestive of endocrine cell proliferation. The results showed these cells to decorate with several endocrine markers, namely, neuron-specific enolase, chromogranin, synaptophysinkeyword, and Leu-7.
A cell linekeyword expressing neuroendocrine (NE) markers, designated as KTS9, was established from a humankeyword large cell carcinoma of the lungkeyword using serum-free medium, ACL-3. KTS9 cells showed morphological characteristics of large cell undifferentiated carcinoma (LCUC) and expressed some general NE markers including neuron-specific enolase (NSEkeyword), protein gene product (PGP) 9.5, neural cell adhesion moleculekeyword (N-CAM), synaptophysinkeyword and neurofilaments (NF) of 200 kd. Such a cell linekeyword derived from LCUC with NE properties has not previously been reported. The biological and NE properties of the KTS9 cell linekeyword were compared with those of 2 surgical cases of LCUC with NE markers. Tumor cells of 2 large cell carcinomas expressed NSEkeyword, PGP9.5, N-CAM and NF.
To establish morphological distinction between phaeochromocytomas and paragangliomas, the universality and differential utility of a panel of tumour markers for diagnosis in formalin-fixed, paraffin-embedded specimens was made. Antibodies to neuron-specific enolase (NSEkeyword), chromogranin, synaptophysinkeyword, Leu-7, neurofilaments, cytokeratins, carcinoembryonic antigen (CEA), melanomakeyword antigen HMB-45, S-100 protein and glial fibrillary acid protein (GFAP), were used on 11 phaeochromocytomas and 8 paragangliomas. Only in 5 phaeochromocytomas was there a focal reaction by neurofilaments. Cytokeratins, CEA and HMB-45 were never detected. We conclude that NSEkeyword, chromogranin, synaptophysinkeyword and S-100 protein are useful markers of both types of tumour, whereas GFAP staining is limited to a small number of these neoplasms. Leu-7 reactivity seems to favour diagnosis of phaeochromocytoma rather than paragangliomakeyword, but further studies with larger series are needed to confirm this. Unlike previous reports, we did not find cytokeratin or HMB-45 immunostainingkeyword in any case.
A case of primary renalkeyword carcinoid has been reported. Immunohistochemical analysis revealed staining for chromogranin A, neuron-specific enolase, Leu-7, and synaptophysinkeyword, as well as pancreatickeyword polypeptide.
This study concerns 45 patients group one suffering from broncho-pulmonary cancer, the diagnosis was obtained by bronchial biopsies or by transparietal puncture using a scanner: there were 35 non-small cell bronchial carcinomas (CNPC) and 10 small cell bronchial cancers (CPC). The control patients (99 patients) were divided up as follows: 44 pleuro-pulmonary infections (group two) and 55 with respiratory failure of various causes other than infectious episodes (group three). In group one the level for TPA was positive in 30 cases (the threshold value was 90 units per litre), 9 for CA 19.9, 7 for ACE and 9 for NSEkeyword. The overall sensitivity was thus better for TPA. There was no correlation between TPA and type of tumour histologykeyword nor between the different markers. Their association did not improve the sensitivity. The NSEkeyword however, remained the most sensitive test for the diagnosis of CPC with six positive tests out of ten. In the control population, the specificity of TPA (66%) was less than that of ACE (100%) or of CA 19.9 (94%) and the false positives were significantly more numerous in group two: 21 patients had a positive test compared to only 12 in group three. Finally the investigators noticed an increase in the level of TPA contrary to other markers, as a function of the extent of the disease from the carcinoma (CNPC unique). The TPA is thus the most sensitive and it turns out to be better reflector to the extent of the tumour disease than either ACE, CA 19.9 or NSEkeyword but this applies uniquely to non-small cell carcinoma.
Two Merkel cell tumor cultures (MC-MA1, MC-MA2) have been established from metastases of typical Merkel cell tumors. The mestastases in vivo were characterized by co-expression of cytokeratins 8, 18, 19, 20 and neurofilaments, presence of intermediate filament whirls, expression of synaptophysinkeyword, neuron-specific enolase, and chromogranin A, rare and weak immunostainingkeyword for plakoglobin but absence of cadherins and desmoplakins. Ultrastructural and immunoelectron microscopic studies of the Merkel cell tumor cells in vitro (MC-MA1, MC-MA2) revealed sparse membrane-bound neuroendocrine granules and typical IFs that were partly arranged in paranuclear whirls and were labeled by antibodies against cytokeratins and neurofilaments. In immunocytochemical studies using antibodies to cytokeratins 8, 18, 19, and 20 and neurofilament protein NF-L, Merkel cell tumor cells in vitro showed a uniform staining appearing as paranuclear whirls and cytoplasmic fibrils as well. Biochemically we found cytokeratins 8, 18, 19, and 20, and NF-L in tumor cells in vitro. These established cell cultures will allow further studies devoted to the biology, differentiation, and hormonekeyword secretion of Merkel cell tumors that may also increase our knowledge about normal Merkel cells.
Two cases of duodenal gangliocytic paragangliomakeyword were studied by means of immunocytochemical methods using 41 kinds of antibodies. The tumors consisted of three histological types; carcinoid, ganglioneuroma and paragangliomakeyword. Tumors of both cases exhibited immunoreactivity to at least one or as many as three of the following: calcitonin, calcitonin-gene related peptide, endocrine granule constituent, Leu7, neuropeptide Y and basic fibroblast growth factorkeyword.
A rare insulin-immunoreactive neuroendocrine tumor of the duodenumkeyword in a 54 year old male has been reported. In addition to positive reactivities of chromogranin A, neuron-specific enolase, synaptophysinkeyword, Leu 7 (CD57), cystatin C, CA15-3 and cytokeratin, the non-argyrophilic tumor cells were strongly immunoreactive for insulin and C-peptide.
The aim of this article was to present a case of primary neuroendocrine tumor (typical carcinoidkeyword) of the mandible that occurred in a 46-year-old black woman who was seropositive for the humankeyword immunodeficiency virus. Immunocytochemical staining showed diffuse, intense positivity for MAK 6, pancytokeratin, S-100, and neuron-specific enolase and focal, intense, positive staining for chromogranin A. Origin from foregutkeyword-derived, immature, and functionally uncommitted endocrine cells is presumed.
One hundred sixty-seven ileal and jejunal carcinoids were retrospectively studied with emphasis on clinical, pathologic, immunohistochemical, and prognostickeyword features. The mean age of patients at the time of presentation was 62 +/- 12 years (range, 13-93 years). Eight patients had carcinoid syndromekeyword (5%) and 1 had Zollinger-Ellison syndrome. Twenty-six percent of tumors were multiple, and 77% were transmurally invasivekeyword; 31% had regional lymph node metastaseskeyword only, and 32% had liverkeyword or mesenteric metastases. Ninety-three percent of tumors had an insular growth pattern. Serotonin was expressed in 86% of tumors (86 of 102), chromogranin in 92%, and neuron specific enolase in 95%. Twenty percent of tumors (10 of 51) expressed prostatic acid phosphatase; 96% were argyrophil, and 98% argentaffin. Of 80 cases with follow-up data (mean follow-up, 52 +/- 5 months), 21% were dead of disease, 16% were dead of other causes, 19% were alive with disease, and 44% had no evidence of disease at last follow-up. The 5-year Kaplan-Meier survival estimate for all cases was 58%. By univariate analysis, survival was negatively correlated with distant metastaseskeyword at the time of surgery (P = 0.002), mitotic rate (P = 0.01), tumor multiplicity (P = 0.01), the presence of carcinoid syndromekeyword (P = 0.02), depth of invasion (P = 0.03), and female gender (P = 0.05); by multivariate analysis, survival was negatively associated with distant metastasis (P = 0.002), carcinoid syndromekeyword (P = 0.01), and female gender (P = 0.03).
Nobels et al evaluate the clinical usefulness of CgAkeyword as neuroendocrine serum marker. Serum levels of CgAkeyword, neuron-specific enolase (NSEkeyword), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgAkeyword, NSEkeyword, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgAkeyword was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSEkeyword was most frequently elevated in patients with small cell lungkeyword carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgAkeyword concentrations. A significant positive relationship was demonstrated between the tumor loadkeyword and serum CgAkeyword levels (P < 0.01, by chi 2 test). Elevated concentrations of CgAkeyword, NSEkeyword, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgAkeyword, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgAkeyword is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSEkeyword and alpha-SU.
A case of malignant neuroendocrine tumor presenting a huge mediastinal mass controlled with radiation therapykeyword has reported. Immunohistochemically the tumor was positive to NSEkeyword and slightly positive to keratin, but negative to LCA, L26, UCLH-1, EMA, Leu7, and chromogranin, suggesting a malignant tumor derived from neuroendocrine tissue.
Key peptide processing enzymes are expressed by a variant form of small-cell carcinoma of the lungkeyword. RT-PCRkeyword for mRNAs representing PC1, PC2, CPEkeyword, and PAM was performed on total RNAkeyword extracted from NCI H82 (a cell linekeyword variant of small-cell carcinoma of the lungkeyword). The primers selected for PCRkeyword and partial sequencing were synthetic 20, 21, 22, and 24 oligomers designed to yield products of 533, 880, 405, and 560 base pairs (bp) for PC1, PC2, CPEkeyword, and PAM, respectively. For the conditions used, the authors were able to demonstrate products for all four enzymes. Each of the four products generated were of the expected size. Cloning and sequencing of these products revealed that each had a structure identical to that published for the humankeyword form of the respective enzyme. Western analysis with antibodies against PC1, PC2, CPEkeyword, and PAM, provided evidence that mRNAs for the four enzymes are translated into proteins that could represent functional forms. These findings therefore demonstrate that key enzymes involved in the generation of active neuropeptides, unlike the marker enzymes NSEkeyword and DDCkeyword, continue to be expressed by variant small-cell carcinoma of the lungkeyword.
To resolve the conflicting diagnoses of five pathologists (which included well-differentiated neuroendocrine carcinoma, malignant carcinoid, undifferentiated small-cell carcinoma, primitive neuroectodermal tumour, metastases of small-cell lungkeyword carcinoma (SCLC) and Merkel cell carcinomakeyword (MCC)), and tumour-free lungs after necropsy, the metastasizing MCC in a 32-year-old Caucasian man was examined using chromosomal in-situ hybridizationkeyword (CISH). Paraffin sections of the thorax, buccal lymph nodes and scalp tumours were stained with haematoxylin and eosin. Immunohistochemistrykeyword was performed with antibodies against pancytokeratin, keratin 20, neuron-specific enolase (NSEkeyword), chromogranin, neurofilaments and vimentin, among others. Although positive for pancytokeratin, keratin 20, chromogranin, NSEkeyword, synaptophysinkeyword and vimentin, the similarity in antigen profiles expressed by SCLC and MCC prevented a definitive tumour diagnosis. Thus, MCC and SCLC have different therapeutic strategies. Chromosomekeyword X may be of prognostickeyword relevance in MCC, which apparently predominates in females and yet shows poorer prognosis in males, and hence be worthy of further investigation.
A primary neuroendocrine carcinoma with ganglion cell differentiationkeyword is described in a crural lymph node. Histologically, the lesion was composed mostly of small cells immunoreactive for cytokeratins, neuron specific enolase and synaptophysinkeyword. Ganglion cells expressed neuron-specific enolase, synaptophysinkeyword, neurofilament proteins and S-100 protein. Moreover, a minority of them featured cytokeratin expression. Although similarities with previous cases of primary neuroendocrine carcinoma of lymph node, ganglion cell differentiationkeyword has never been described.
A new case of primary Merkel cell carcinomakeyword (MCC) of the vulva is reported and the literature reviewed for noting its clinical presentation, microscopic, immunohistochemical and ultrastructural features, as well as for establishing the role of immunohistochemistrykeyword in the ultimate diagnosis of this uncommon and aggressive tumor. The immunohistochemical study showed positivity for wide spectrum and low molecular weight cytokeratins, epithelial membrane antigen, neurofilaments, neuron specific enolase and chromogranin A. The coexpression of cytokeratins (including cytokeratin 20) and neurofilaments, both in typical globular paranuclear arrangement, made possible the diagnosis of MCC, differentiating it from other malignant small cell tumors such as neuroendocrine metastatickeyword carcinoma.
A 58-year-old male patient complaining of pain in the right lower quadrant was diagnosed with acute appendicitis and underwent an appendectomy. Histological examination of the resected appendixkeyword revealed goblet cell carcinoid. The expression of beta-catenin and E-cadherinkeyword was investigated to compare with that of typical rectal carcinoids (n = 3) and colonkeyword adenocarcinomas (n = 3). In normal colonic and rectal mucosae, beta-catenin and E-cadherinkeyword stained positive on the plasma membrane. In the case reported here, beta-catenin showed a preserved expression on the plasma membrane of goblet cell carcinoid; a pattern similar to typical carcinoids rather than to adenocarcinomas. This staining pattern was identical to those both of carcinoids and of adenocarcinomas. These findings suggest the possibility that, in some cases, the adherens junctions of goblet cell carcinoids are similar to those of typical carcinoids rather than to those of adenocarcinomas.
In this study, the establishment and characterisation of a cell linekeyword derived from the lymph-node metastasis of a patient with highly aggressive Merkel cell carcinomakeyword (MCC) is reported. Merkel carcinoma cells (MCC-1) grew as floating aggregates in suspension cultures for more than two years and over 70 subcultures. The immunocytochemical pattern of the cultured MCC-1 was similar to that of the original tumor with expression of cytokeratin 18, neuron-specific enolase, neurofilaments, and synaptophysinkeyword. In addition, reverse transcriptase polymerase chain reaction (RT-PCRkeyword) revealed presence of chromogranin A mRNA in the MCC-1 cell linekeyword. Furthermore, electron microscopykeyword yielded the rare finding of neuroendocrine granules in the cytoplasm of the cultured cells. The cell linekeyword MCC-1 was able to form colonies in soft agar. The MCC-1 line may thus serve as a model for studying the biology and the metastatickeyword potential of Merkel cell carcinomakeyword.
Five cases of spindle cell carcinoids of the lungkeyword were analyzed by immunohistochemical and ultrastructural technique. They were found to be biphasic tumors composed of the major component of neuroendocrine cells (chief cells) and a minor component of dendritic cells (supporting cells). The supporting cells were dendritic in appearance and displayed strong positivity for S-100 protein in all cases. It is proposed that pulmonary carcinoids with biphasic features are better designated as gangliocytic paragangliomas of the lungkeyword rather than paraganglioid carcinoids.
A case study of a 46-year-old Japanese man with a metastatickeyword skin tumor on his left palmar region. He underwent resectionkeyword for a mediastinal neuroendocrine carcinoma in February of 1998. After the operation, he immediately noticed an elevated tumor on his left palm. In September 1999, a brain tumor was discovered. The skin and brain tumors were subsequently removed surgically. Neuron specific enolase (NSEkeyword) in the serum was elevated to 25 ng/ml. A skin biopsykeyword specimen from the left palmar site revealed multiple tumor nests which showed the same histological features as the primary mediastinal tumor. Immunostainingkeyword was positive for chromogranin, synaptophysinkeyword, and NSEkeyword but negative for S-100 protein and CD57.
The authors report a unique case of a combined pulmonary large-cell neuroendocrine carcinoma and spindle-cell carcinoma. The left upper lobectomy specimen revealed an 8.0-cm mass with central necrosis. The spindle cells were positive for low-molecular-weight keratin and vimentin with focal expression of CD68 and muscle-specific actin. The combination of neuroendocrine malignancies and spindle-cell carcinomas appears to be uncommon in the lungkeyword.
The group of 35 carcinoid tumours obtained from 34 patients was reviewed according to recent histopathological criteria. Consequently, evaluation of the Grimelius staining and immunohistochemical detection of chromogranin A (CgAkeyword), Leu-7 (CD-57), synaptophysinkeyword, neuron-specific enolase (NSEkeyword), (beta-III tubulin, Ki-67keyword and proliferating cell nuclear antigen (PCNAkeyword) was performed. Thirty-four tumours (97.1%) showed granular cytoplasmic positivity for both markers of neuroendocrine granules (CgAkeyword and Leu-7). One tumour (2.9%) was positive only for Leu-7.
A case of gastrickeyword carcinoid tumor with ossification is reported. Histologically, the tumor was widely occupied by mature bone tissues, where scattered carcinoid tumor cell nests surrounded bone tissues or located in stromal areas. Immunohistochemically, the tumor cells were strongly positive for cytokeratin, chromogranin A, synaptophysinkeyword, neurofilaments and neuron-specific enolase, underscoring the diagnosis of carcinoid tumor. There are only four cases in the world literature, including a current case of ossifying gastrickeyword carcinoid tumor, in which the excessive production of peptides promoting ossification was considered to be implicated in the unusual appearance of the bone.
Sixty-three neuroendocrine tumors positive for one or more immunohistochemical marker of neuroendocrine differentiationkeyword (chromogranin A, chromogranin B, synaptophysinkeyword, secretogranin II, neuron-specific enolase) were selected for the study and consisted of 34 typical carcinoids (15 pulmonary, 11 ileal, 4 gastrickeyword, and 4 rectal), 19 PETs, and 10 pheochromocytomas (4 sporadic, 3 MEN-2, 2 neurofibromatosiskeyword type 1, and 1 VHLkeyword). All cases were stained for NESP-55 after microwave antigen retrieval using a rabbit polyclonal antibodykeyword. NESP-55 immunoreactivity was seen as brown finely granular cytoplasmic staining with prominent perinuclear accentuation. All gastrickeyword and ileal carcinoids studied were completely negative for NESP-55. One of four rectal and 1 of 15 pulmonary carcinoids showed focal positivity for it in less than 5% of tumor cells. In contrast, all 10 pheochromocytomas and 14 of 19 PETs showed strong immunohistochemical staining in a variable proportion of tumor cells. Diffuse positivity (>75% of tumor cells) was seen in 6 of 14 PETs and 8 of 10 pheochromocytomas. These results indicate that, in contrast to the other granins, NESP-55 reactivity is restricted to endocrine tumors of the pancreas and the adrenal medulla. Immunohistochemical expression of NESP-55 may thus be useful in assigning a pancreatickeyword or adrenal origin to metastatickeyword endocrine tumors of unknown originkeyword.
The prevalence and distribution of neuroendocrine differentiationkeyword in non-small cell lung cancerkeyword (NSCLC) was estimated by assays for synaptophysinkeyword (SYN), chromogranin A (CgAkeyword), Leu7 and neuron-specific enolase (NSEkeyword). Serum NSEkeyword <12.5 ng/mL and serum CgAkeyword <46 U/L were taken as cutoff levels. RESULTS: 63.8% (37/58) of NSCLC were scored as NE1-NE4 according to the SYN, CgAkeyword and Leu7 levels; 34.5% as NE1; 29.3% as NE2-NE4. 56.8% of tumors were positive for SYN, 34.4% for CgAkeyword, 22.4% for Leu7, and 79.3% for NSEkeyword.
The differential expression of secretagogin in normal mucosa, adenocarcinomas, and neuroendocrine tumors has been investigated. Western blottingkeyword, immunohistochemistrykeyword, immunofluorescencekeyword microscopykeyword and ELISAkeyword were applied. Western blot analysis detected a 32-kDa secretagogin band in samples from normal mucosa. Immunohistochemical analyses on tissue specimens showed that secretagogin is exclusively expressed in neuroendocrine cells and nerve cells in normal mucosa of the digestive tract. Tissues adjacent to benign hyperplasic polyps and adenomas showed a decreased number of secretagogin-expressing neuroendocrine cells. Secretagogin co-localized with neuroendocrine markers (chromogranin A, neuron-specific enolase, synaptophysinkeyword) in neuroendocrine cells in crypts of normal mucosa, and in tumor cells of carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of 19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as well as in neuroendocrine tumors from the lungkeyword, pancreas and adrenal gland. Secretagogin was detected in plasma from carcinoid patients with distant metastasis. Combined immunohistochemical analysis of secretagogin and FK506-bindingkeyword protein 65, a protein de novo synthesized in adenocarcinomas, distinguished well-differentiated carcinoids, adenocarcinoids and undifferentiated carcinomas. Secretagogin is a novel marker for neuroendocrine differentiationkeyword.
The authors present the case of a 55-year-old woman with cervical metastases almost 3 years after a primary diagnosis of temporal bone carcinoid. Histologic examination after the neck dissection was suggestive of lymph node metastaseskeyword from a carcinoid tumor. Immunohistochemical analysis of the lymph node metastaseskeyword showed neoplastic cells positive for vimentin.
Gastrointestinalkeyword (GI) carcinoid tumor cell lines were analyzed by RT-PCRkeyword and immunoblot and repression of tryptophan hydroxylase 1 mRNA was noted.
Secretagogin (SCGNkeyword) expression in normal and tumor tissues from various organ sites compared with three other conventional neuroendocrine markers [chromogranin A (CgAkeyword), neuron specific enolase, and synaptophysinkeyword]. Strong SCGNkeyword staining was found in most normal neuroendocrine tissues except in the adrenal cortex. SCGNkeyword expression was identified in 140 out of 213 neuroendocrine tumors and 12 conventional carcinomas with neuroendocrine differentiationkeyword. In a subset of neuroendocrine tumors, such as gastrickeyword neuroendocrine cancers and typical carcinoidkeyword tumors of rectumkeyword and ovary, SCGNkeyword showed strong staining while CgAkeyword expression was often negative. It is intriguing to note that SCGNkeyword staining was positive in 26 out of 31 small cell lungkeyword cancers, more frequently than the other three markers. SCGNkeyword is a novel neuroendocrine marker that may be useful in routine surgical pathology practice.
We assessed the usefulness of several immunohistochemical stains in distinguishing these two neoplasms, including cytokeratin 7, cytokeratin 20 (CK20), neuron-specific enolase, chromogranin, synaptophysinkeyword, neurofilaments (NF), thyroid-transcription factorkeyword-1 (TTF-1), CD56keyword antigen, S-100 protein, vimentin, c-erbB-2 oncoprotein, and CD117 antigen. Twelve of 13 Merkel cell carcinomakeyword cases were positive for NF. All small cell lungkeyword carcinoma cases were negative for NF, and all but one were negative for CK20. These findings suggest that a set of three immunohistochemical stains, including CK20, NF, and TTF-1, is useful in affording a distinction between Merkel cell carcinomakeyword and small cell lungkeyword carcinoma.
In 43 patients with carcinoid tumors somatostatin serum level, 5-HIAAkeyword (5-hydroxyindolacetic acid), NSEkeyword (neuron-specific enolase), and chromogranin A were examined. Fifteen patients received 30mg of somatuline (Lanreotid) in two-week intervals. Therapykeyword with somatostatin analogue improved symptoms in 70-80% of patients with metastases and carcinoid syndromekeyword. 5-HIAAkeyword significantly decreased after lanreotid therapykeyword. NSEkeyword values are undulating. With progressionkeyword of the disease they rise. Chromogranin is higher in patients with advanced metastatickeyword disease. Mesor of the diurnal excretion of somatostatin is higher (32 pg/mL) in patients with metastatickeyword disease than in patients without (20 pg/mL). After lanreotid administration mesor decreased (16 pg/mL) in the group of patients with metastases.
The immunoreactivity for secretagogin has been analyzed in consecutive sections from 87 formalin-fixed paraffin-embedded (FFPE) benign hyperplastic (n = 10) and prostatekeyword adenocarcinoma (n = 77) specimens. The intracellular distribution of secretagogin was examined by confocal fluorescent microscopykeyword, and characterized secretagogin in eight samples by Western blottingkeyword. Secretagogin is cytoplasmic and nuclear expressed in NE and NE differentiated cells, and to a lesser extent in epithelial cells, in the benign prostatekeyword and prostatekeyword adenocarcinoma cells. Secretagogin stained 82% (46/56) of benign and 71% (48/68) of prostatekeyword adenocarcinomas and co-localized with the NE markers CgAkeyword and NSEkeyword. The expression of secretagogin is significantly correlated to CgAkeyword (P < 0.001) and NSEkeyword (P < 0.048) in prostatekeyword adenocarcinoma and to CgAkeyword in normal epithelium (P < 0.028). Secretagogin is a novel NE marker in the prostatekeyword with more extended immunoreactivity compared to the NE markers CgAkeyword, SYN, and NSEkeyword. Secretagogin is widely expressed in prostatic adenocarcinoma as opposed to adenocarcinomas in other organs.
The long-term postsurgical outcome of a single-institution series of 67 radically treated bronchopulmonary carcinoids was correlated with the tumor phenotype assessed by combining conventional histologykeyword with a panel of immunohistochemical markers exploring cell differentiationkeyword (chromogranin, NSEkeyword, TTF1keyword), cell turnover (Mib1keyword), and apoptosiskeyword (Bcl2keyword, Baxkeyword). All cases expressed all neuroendocrine markers except TTF1keyword. At univariate analysis, tumor recurrence (n = 6) correlated significantly with Bcl2keyword expression (P = 0.024). The best cutoffs for Bcl2keyword expression (calculated by receiver operating characteristic curves) discriminating recurrent versus nonrecurrent tumors was 2.0% for Bcl2keyword (Bcl2keyword: sensitivity, 83%; specificity, 65%; area under curve, 0.769 +/- 0.12). By stratifying the patients according to the obtained cutoffs, significant differences emerged in the patients' disease-free survivalkeyword (log-rank test: Bcl2keyword, P = 0.01). The authors concluded that Bcl2keyword significantly discriminates between recurrent versus nonrecurrent tumors, producing a biologically plausible, diagnostically suitable immunohistochemical pattern.
In this study, two examples of Merkel cell carcinomakeyword developed within epithelial cysts are described. Neoplastic cells of Merkel cell tumor expressed immunoreactivity for chromogranin, synaptophysinkeyword, neuron-specific enolase, CAM 5.2 and cytokeratin 20, the last two markers showing the characteristic paranuclear dot-like pattern. In contrast, the epithelial wall lining the cyst and surrounding Merkel cell tumor only expressed immunoreactivity for cytokeratin MNF116. The description of five cases of Merkel cell carcinomakeyword within follicular cysts, including the two cases of this report, support some relationship between Merkel cell tumor and the hair follicle.
The aim of our work was to confirm an immunohistochemical profile of routine markers of epithelial and neuroendocrine differentiationkeyword in eleven cases of Merkel cell carcinomakeyword, In all the investigated tumours the characteristic "dot-like" pattern of cytokeratin 20 immunoexpression, as well as negative immunostainingkeyword for cytokeratin 7 and thyroid transcription factorkeyword 1 (TTF-1) were disclosed; An interesting finding was observed when the anti-cytokeratin monoclonal antibodykeyword MNF 116 was used. The characteristic "dot-like" pattern was detected in high proportion of tumours, including two samples of local recurrence of one of the carcinomas, where neoplastic cells have lost the expression of cytokeratin 20.
To examine whether immunocytochemistry can distinguish pulmonary large cell neuroendocrine carcinoma (LCNECkeyword) among non-small cell lungkeyword cancers (NSCLCs). Tumor touch imprint cytologic specimens of 109 lungkeyword cancers were studied by Immunocytochemistry using 8 primary antibodies: chromogranin A, synaptophysinkeyword, neural cell adhesion moleculekeyword, neuron specific enolase, CK34betaE12, thyroid transcription factorkeyword-1, cytokeratin 18 and E-cadherinkeyword. If 2 or 3 antibodies of chromogranin A, synaptophysinkeyword and neural cell adhesion moleculekeyword were stained positive and CK34betaE12 was not stained, pulmonary LCNECkeyword can be selected accurately among other NSCLCs with 100% sensitivity and 100% specificity.
The authors report the case of a moderately differentiatedkeyword neuroendocrine carcinoma NECkeyword (atypical carcinoidkeyword) of the larynx in a heavy smoker 67-year-old woman. The lesion was biopsied and microscopic examination revealed moderately differentiatedkeyword NECkeyword. On immunohistochemical analysis, overexpression of p53 protein was noted. The authors concluded that this neoplasm was not due to an HPV infection, but a mutation of p53 gene which could cause mmunohistochemical overexpression of p53 protein.
Thirty-three consecutive patients (22 men and 11 women; mean age +/- SD, 57.8 +/- 12.1 y) were investigated at baseline and again 3 mo after initiation of the first cycle of PRRT. (68)Ga-DOTATATE receptorkeyword expression was assessed using 2 measures of standardized uptake value (SUV): maximum SUV (SUV(max)) and tumor-to-spleen SUV ratio (SUV(T/S)). Percentage change in SUV scores after PRRT relative to baseline (DeltaSUV) was calculated. After completing 1-3 cycles of PRRT, patients entered the follow-up study, for estimation of time to progressionkeyword. According to the Response Evaluation Criteria in Solid Tumors, progressionkeyword was defined on the basis of contrast-enhanced CTkeyword. Clinical symptoms, as well as the tumor markers chromogranin A and neuron-specific enolase, were also recorded during regular follow-up visits. The 23 of 31 patients with decreased SUV(T/S) after the first PRRT cycle had longer progressionkeyword-free survival than did the 8 of 31 patients with stable or increased scores (median survival not reached vs. 6 mo, P = 0.002). For the 18 of 33 patients showing a reduction in SUV(max), there was no significant difference in progressionkeyword-free survival (median survival not reached vs. 14 mo, P = 0.22). Multivariate regression analysis identified SUV(T/S) as the only independent predictor for tumor progressionkeyword during follow-up. In the 17 of 33 patients with clinical symptoms before PRRT, DeltaSUV(T/S) correlated with clinical improvement (r = 0.52, P < 0.05), whereas DeltaSUV(max) did not (r = 0.42, P = 0.10). Changes in the tumor markers (chromogranin A and neuron-specific enolase) did not predict DeltaSUV scores, clinical improvement, or time to progressionkeyword.
Gilbert assessed 104 NETs (74 cases) for biomarkers targeted by anticancer drugs under development for other forms of cancer. Activating mutations were assessed in epidermal growth factorkeyword receptorkeyword (EGFRkeyword), stem cell factor receptorkeyword (KITkeyword), and platelet-derived growth factorkeyword receptorkeyword alpha (PDGFRA), as well as non-response mutations in KRASkeyword. Copy number of EGFRkeyword and HER-2/neu was quantified with fluorescence in situkeyword hybridizationkeyword. Immunohistochemical analyses were performed for EGFRkeyword, KITkeyword, PDGFRA, somatostatin receptorkeyword subtypes 2A and 5 (SSTR5keyword), vascular endothelial growth factorkeyword receptorkeyword 1, mammalian target of rapamycin (mTORkeyword), insulin-like growth factorkeyword 1 receptorkeyword (IGF1Rkeyword), heat shock protein 90 (Hsp90), and transforming growth factorkeyword-beta receptorkeyword 1 (TGFBR1). NETs lacked HER2-overexpression predictive of anti-HER2 response and KITkeyword and PDGFRA activating mutations indicative of imatinibkeyword sensitivity. High EGFRkeyword aneusomy (20% of all cases) and elevated EGFRkeyword copy number (39%) were found, but few KRASkeyword mutations associated with non-response to anti-EGFRkeyword therapykeyword (3%). Hsp90, TGFBR1, IGF1Rkeyword, and SSTR5keyword exhibited highest levels of immunohistochemical staining in the largest percents of tumors. In subsequent in vitro studies, anticancer drug 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) (targetingkeyword Hsp90) inhibited proliferation of BP NET lines NCI-H727, NCI-H720, and NCI-H835 with IC(50) values of 70.4, 310, and 788 nM respectively; BMS-754807 (targetingkeyword IGF1Rkeyword/IR) inhibited growth with IC(50) values of 428 nM, 2.8 microM, and 1 microM. At growth-inhibiting concentrations, 17-AAG (24 h) induced loss of EGFRkeyword and IGF1Rkeyword in the IGF1Rkeyword-expressing NCI-H727 line, and BMS-754807 (24 h) inhibited constitutive IGF1Rkeyword autophosphorylation.
A 46-year-old woman was hospitalized with a preoperative diagnosis of gallbladderkeyword carcinoma, The patient was referred for surgical opinion and laparotomy was subsequently performed. A 4 x 5 cm mass was found within the gallbladderkeyword, located on the free surface of the body and fundus of the gallbladderkeyword. Neither metastases nor direct invasion to the liverkeyword was found. The entire mass and gallbladderkeyword were excised and intact. Histologically, the tumor consisted of small oval cells with round-to-oval neclei and tumor cells formed small nodular, trabeculare and acinar structures. The tumor showed moderate pleomorphism with scattered mitotic figures, but no definite evidence of vascular permeation, perineural invasion or lymphatic permeation was seen. The tumor cells invaded the mucosa extensively, and some penetrated the muscular layer but not through the serosa of the gallbladderkeyword into the liverkeyword. Immunohistochemical studies revealed strong positive reaction for chromogranin A and NSEkeyword. This lesion was proved to be a primary carcinoid tumor of the gallbladderkeyword. A brief review of literature, clinical feature, pathology and treatment of this rare disease was discussed.
Two methods of evaluation of hemolysis have been compared: the determination of free haemoglobin (Hb) by spectrophotometrykeyword and the indirect measurement of an hemolytic index with a multiparameter analyzer, the Modular (Roche Diagnostics). The correlation between these 2 methods on 42 samples is very satisfactory: Y (free Hb) = 12.337 X (index) + 31.743 r = 0.997. The NSEkeyword assay is based on TRACE (Time Resolved Amplified Cryptate Emission) technology, on a Kryptor (BRAHMS). The influence of hemolysis on the determination of NSEkeyword was confirmed by overloading with hemoglobin (hemolysate) 3 pools of serum with NSEkeyword concentrations close to the threeshold decision. The determination of NSEkeyword shows an increase in concentration parallely to the hemolytic index (about 150% for an hemolytic index of 10). Consequently, the NSEkeyword determination is realized only for samples presenting an hemolytic index < or = 10, this allowing a good monitoring of kinetics of this marker.
The long-term post-surgical outcome of 106 radically treated patients affected by bronchopulmonary carcinoid from two Italian centers was correlated with tumor characteristics assessed by combining conventional histologykeyword with a panel of immunohistochemical markers of neuroendocrine differentiationkeyword (chromogranin-A, NSEkeyword) and proliferation activity (Ki-67keyword score). Carcinoids were assessed as typical (TC = 75; 70.8%) and atypical (AC = 31; 29.2%). Mean follow-up was 8.3 years (range: 0–20; median: 8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid histotype (P = 0.003), tumor sizekeyword (P = 0.012), mitotic index (P = 0.044), Ki-67keyword score (P < 0.0001), and synchronous node metastasis (P = 0.037). Of these, Cox multivariate analysis confirmed only Ki-67keyword score as independent predictor of disease recurrence (P = 0.009). The best cut-off for Ki-67keyword score (calculated by ROC curves) discriminating recurrent vs non-recurrent disease was 4% (sensitivity 79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients according to this cut-off, a significantly different disease-free survivalkeyword was found (log-rank test P < 0.0001).
Primary neuroendocrine tumors of the kidney: morphological and molecular alterations of an uncommon malignancy --- Patients included 5 men and 6 women with a median age of 50 years. These tumors occurred in the left (5/11), right (3/11), and horseshoe (1/11) kidney. The histologic patterns were predominantly solid, trabecular, and pseudoglandular. Lymphovascular invasion and calcification were found in 3 and 1 cases, respectively. There were 2 atypical and 9 typical carcinoids. At the time of surgery, 2 patients with atypical carcinoids had hepatic metastasis, and 1 of the typical carcinoidkeyword patients had lymph node metastasis. All cases showed <1% proliferative rate, except 2 cases with hepatic metastasis, which showed 3% to 5% with MIB1keyword/Ki-67keyword immunostainingkeyword. Immunostainings were frequently positive for synaptophysinkeyword, chromogranin, CD56keyword, CD99keyword, and neuron-specific enolase. Follow-up data (average 4 years) were available for 6 patients. Two patients with distant metastasis were alive with disease, and four patients with no metastasis were alive without disease. We evaluated the association of PNRT and loss of heterozygositykeyword (LOH) on chromosomekeyword 3p21 and found LOH in 2 of 3 cases. However, the comparative genomic hybridizationkeyword study (2/2) did not demonstrate significant chromosomal imbalances.
Biological Variation of Neuroendocrine Tumor Markers Chromogranin A and Neuron-Specific Enolase -- We collected five blood specimens from each of 22 healthy volunteers (10 men and 12 women, 23-54years) on the same day every two weeks for two months. Serum specimens were stored at -80 degrees C until analysis and analyzed in a single run in duplicate. Data were analyzed by the ANOVA. RESULTS: Serum CgAkeyword concentrations were significantly higher for women than for men (P=0.01), whereas no difference was found for NSEkeyword. Intra-individual variance was not different between genders for both biomarkers. Within- and between-subject CVs were 16.3% and 33.5% for CgAkeyword and 13.6% and 11.5% for NSEkeyword, respectively. CgAkeyword showed marked individuality, suggesting that the use of population-based reference limits is inadequate for its interpretation. Conversely, the low individuality of NSEkeyword allows the use of a single reference interval. Reference change values were 46% for CgAkeyword and 39% for NSEkeyword. Desirable analytical goals for imprecision, bias, and total error were <8.2%, +/-9.3%, and +/-22.8% for CgAkeyword, and <6.8%, +/-4.5%, and +/-15.7% for NSEkeyword, respectively.

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