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W G Mccluggage - One of the best experts on this subject based on the ideXlab platform.
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inhibin is more specific than Calretinin as an immunohistochemical marker for differentiating sarcomatoid granulosa cell tumour of the ovary from other spindle cell neoplasms
Journal of Clinical Pathology, 2003Co-Authors: V I Shah, O N Freites, Patrick H Maxwell, W G MccluggageAbstract:Aims: To describe a case of recurrent sarcomatoid adult granulosa cell tumour (AGCT) of the ovary and to evaluate the usefulness of two ovarian sex cord stromal markers (inhibin and Calretinin) in separating sarcomatoid AGCT from true sarcomas. Methods: A 72 year old woman presented with a recurrent sarcomatoid AGCT in the sigmoid colon mesentery, which histologically mimicked a malignant gastrointestinal stromal tumour (GIST). This index case and 79 sarcomas (32 GISTs, 28 leiomyosarcomas, 15 endometrial stromal sarcomas (ESSs), including one with sex cord-like areas, and four undifferentiated uterine sarcomas) were immunostained using antibodies to inhibin and Calretinin. Results: The recurrent sarcomatoid AGCT expressed diffuse, strong cytoplasmic immunoreactivity with inhibin and focal but strong nuclear and cytoplasmic positivity with Calretinin. Focal, weak cytoplasmic inhibin expression limited to sex cord-like areas was present in one ESS. None of the other sarcomas expressed inhibin. Focal, strong Calretinin immunoreactivity was identified in 11 leiomyosarcomas and one GIST. The case of ESS with sex cord-like areas showed strong immunoreactivity for Calretinin limited to the sex cord-like areas. Conclusions: Inhibin is a useful immunomarker to distinguish sarcomatoid AGCT from other spindle cell neoplasms that may enter into the differential diagnosis. Calretinin appears to be less specific than inhibin.
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immunohistochemical staining for Calretinin is useful in the diagnosis of ovarian sex cord stromal tumours
Histopathology, 2001Co-Authors: W G Mccluggage, Patrick H MaxwellAbstract:Immunohistochemical staining for Calretinin is useful in the diagnosis of ovarian sex cord–stromal tumours Aims: Ovarian sex cord–stromal tumours are a heterogeneous group of neoplasms which may be confused morphologically with a wide variety of tumours. Calretinin positivity has previously been demonstrated in a small number of ovarian sex cord–stromal tumours. The aim of this study was to investigate Calretinin staining in a series of these tumours and their histological mimics in order to determine the value of Calretinin staining in a diagnostic setting. Methods and results: Seventy-two neoplasms, including 37 ovarian sex cord–stromal tumours and 35 miscellaneous neoplasms which may enter into the differential diagnosis, were stained with a commercially available polyclonal antibody against Calretinin. All sex cord–stromal tumours exhibited positivity except for a single fibrothecoma. In this group of tumours staining was generally diffuse and strong. Small numbers of the miscellaneous group of neoplasms exhibited positivity but this tended to be focal and weak, although this was not always the case. There was consistent strong positive staining of granulosa cells in follicular cysts and corpora lutea. There was also positive staining of luteinized stromal cells in two cases of ovarian stromal hyperplasia and hyperthecosis. Conclusions: Calretinin is a sensitive immunohistochemical marker of ovarian sex cord–stromal tumours and may be useful in a diagnostic setting. However, the value is somewhat limited since occasional neoplasms which enter into the morphological differential diagnosis may be positive. Be that as it may, Calretinin positivity may be of value in the diagnosis of an ovarian sex cord–stromal tumour and its differentiation from other neoplasms. In this regard, Calretinin should always be used as part of a larger panel.
Patrick H Maxwell - One of the best experts on this subject based on the ideXlab platform.
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inhibin is more specific than Calretinin as an immunohistochemical marker for differentiating sarcomatoid granulosa cell tumour of the ovary from other spindle cell neoplasms
Journal of Clinical Pathology, 2003Co-Authors: V I Shah, O N Freites, Patrick H Maxwell, W G MccluggageAbstract:Aims: To describe a case of recurrent sarcomatoid adult granulosa cell tumour (AGCT) of the ovary and to evaluate the usefulness of two ovarian sex cord stromal markers (inhibin and Calretinin) in separating sarcomatoid AGCT from true sarcomas. Methods: A 72 year old woman presented with a recurrent sarcomatoid AGCT in the sigmoid colon mesentery, which histologically mimicked a malignant gastrointestinal stromal tumour (GIST). This index case and 79 sarcomas (32 GISTs, 28 leiomyosarcomas, 15 endometrial stromal sarcomas (ESSs), including one with sex cord-like areas, and four undifferentiated uterine sarcomas) were immunostained using antibodies to inhibin and Calretinin. Results: The recurrent sarcomatoid AGCT expressed diffuse, strong cytoplasmic immunoreactivity with inhibin and focal but strong nuclear and cytoplasmic positivity with Calretinin. Focal, weak cytoplasmic inhibin expression limited to sex cord-like areas was present in one ESS. None of the other sarcomas expressed inhibin. Focal, strong Calretinin immunoreactivity was identified in 11 leiomyosarcomas and one GIST. The case of ESS with sex cord-like areas showed strong immunoreactivity for Calretinin limited to the sex cord-like areas. Conclusions: Inhibin is a useful immunomarker to distinguish sarcomatoid AGCT from other spindle cell neoplasms that may enter into the differential diagnosis. Calretinin appears to be less specific than inhibin.
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immunohistochemical staining for Calretinin is useful in the diagnosis of ovarian sex cord stromal tumours
Histopathology, 2001Co-Authors: W G Mccluggage, Patrick H MaxwellAbstract:Immunohistochemical staining for Calretinin is useful in the diagnosis of ovarian sex cord–stromal tumours Aims: Ovarian sex cord–stromal tumours are a heterogeneous group of neoplasms which may be confused morphologically with a wide variety of tumours. Calretinin positivity has previously been demonstrated in a small number of ovarian sex cord–stromal tumours. The aim of this study was to investigate Calretinin staining in a series of these tumours and their histological mimics in order to determine the value of Calretinin staining in a diagnostic setting. Methods and results: Seventy-two neoplasms, including 37 ovarian sex cord–stromal tumours and 35 miscellaneous neoplasms which may enter into the differential diagnosis, were stained with a commercially available polyclonal antibody against Calretinin. All sex cord–stromal tumours exhibited positivity except for a single fibrothecoma. In this group of tumours staining was generally diffuse and strong. Small numbers of the miscellaneous group of neoplasms exhibited positivity but this tended to be focal and weak, although this was not always the case. There was consistent strong positive staining of granulosa cells in follicular cysts and corpora lutea. There was also positive staining of luteinized stromal cells in two cases of ovarian stromal hyperplasia and hyperthecosis. Conclusions: Calretinin is a sensitive immunohistochemical marker of ovarian sex cord–stromal tumours and may be useful in a diagnostic setting. However, the value is somewhat limited since occasional neoplasms which enter into the morphological differential diagnosis may be positive. Be that as it may, Calretinin positivity may be of value in the diagnosis of an ovarian sex cord–stromal tumour and its differentiation from other neoplasms. In this regard, Calretinin should always be used as part of a larger panel.
David M Jacobowitz - One of the best experts on this subject based on the ideXlab platform.
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Developmental expression of Calretinin-immunoreactivity in the thalamic eminence of the fetal mouse.
International Journal of Developmental Neuroscience, 1999Co-Authors: Louise C. Abbott, David M JacobowitzAbstract:Abstract An investigation of the developmental expression of Calretinin immunoreactivity and mRNA expression was carried out in the developing mouse diencephalon. Attention was focused on the thalamic eminence, which is a prominent structure previously described in the thalamus of the fetal mammalian diencephalon and adult lower vertebrates. Calretinin-positive staining was first observed in the thalamic eminence beginning at embryonic day 11. In situ hybridization histochemistry confirmed the presence of Calretinin mRNA in the thalamic eminence. During subsequent embryonic development Calretinin expression was very intense in neurons in the thalamic eminence though embryonic day 17, and thereafter, was increasingly difficult to distinguish. By postnatal day 0 the thalamic eminence was no longer discernable. Additional neurons within the murine diencephalon also expressed Calretinin positive cell bodies and/or neuronal processes, including the stria medullaris, the habenular commissure and the paraventricular thalamic nucleus. It is possible that the thalamic eminence may form during development in order to act as an organizing center for the diencephalon.
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The mouse Calretinin gene promoter region: structural and functional components
Molecular Brain Research, 1997Co-Authors: Kenneth I. Strauss, Lois Winsky, Jacek Kuźnicki, Jun Ichi Kawagoe, Michael Hammer, David M JacobowitzAbstract:Abstract The 5′ flanking region of the mouse Calretinin gene was cloned and a 1.8 kbp region adjacent to exon 1 was sequenced. Putative upstream promoter and enhancer elements were identified, including appropriately positioned TATA and CAAT boxes (positions −50 and −68, respectively). There was considerable sequence and structural homology between mouse and human upstream elements. Neuron-restrictive activity was demonstrated via transfection of Calretinin promoter-reporter constructs into primary embryonic mouse brain cultures expressing Calretinin. In promoterless reporter constructs, the proximal upstream 1.5 kbp of the mouse Calretinin gene boosted luciferase activity (up to 100-fold) exclusively in the neuronal population. Deletion analysis revealed the minimal promoter to be within the 95-bp proximal to the transcription start site. Transfections with SV40 promoter constructs in these cultures resulted in reporter gene expression predominantly in non-neuronal cells. Inserting the proximal 1.5 kbp of mouse Calretinin upstream in SV40 promoter-reporter constructs reduced luciferase activity. Thus, Calretinin upstream sequences increased reporter expression in cultured neurons and decreased expression from the SV40 promoter in non-neuronal cultured brain cells. The Calretinin promoter contained relevant regulatory element consensus motifs and demonstrated in vitro neuron-restrictive bioactivity.
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Calretinin-Containing Neurons in Rat Cerebellar Granule Cell Cultures
Brain Research Bulletin, 1997Co-Authors: Ann M. Marini, Kenneth I. Strauss, David M JacobowitzAbstract:Using an antiserum against Calretinin, a calcium-binding protein, we discovered two distinct neuronal cell types that stain intensely in enriched cerebellar granule cells. One neuronal cell type resembles unipolar brush cells, whereas the other resembles Lugaro cells. During early culture times, these Calretinin-positive neurons are most numerous but represent less than one percent of the total neuronal population. In cultured cells, Calretinin mRNA levels peak at day three in vitro, followed by a rapid decline to undetectable levels by day six in vitro. However, Calretinin-immunoreactive neurons are observed up to 29 days in vitro. Excitotoxic concentrations of glutamate receptor agonists failed to elicit an excitotoxic response on the intensely staining Calretinin-positive neurons, whereas greater than 95% of the cerebellar granule cells were susceptible to the excitotoxic actions of the glutamate receptor agonists. To distinguish between the two possibilities that Calretinin-positive neurons either do not express glutamate receptors or they are not susceptible to the excitotoxic effects of glutamate receptor agonists, we performed immunocytochemistry using glutamate receptor antibodies to detect the presence of receptor protein. We found that the AMPA/kainate glutamate receptor (GluR2R3) colocalized with Calretinin, suggesting that Calretinin-immunoreactive neurons express the AMPA/kainate receptor; cerebellar granule cells, which are known to express this receptor, were also immunoreactive for the GluR2R3 receptor.
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Calretinin mRNA and immunoreactivity in the medullary reticular formation of the rat: colocalization with glutamate receptors.
Brain research, 1996Co-Authors: Lois Winsky, K R Isaacs, David M JacobowitzAbstract:Calretinin-positive cells were identified in the medullary reticular formation of the rat by both immunohistochemistry and in situ hybridization histochemistry. In addition, double immunocytochemical labeling was used to examine the degree of colocalization of Calretinin with GluR2/R3, GluR4 and GluR5-7 glutamate receptor subtypes. Results indicated regional variation in Calretinin expression across reticular formation regions with the exception of the largest cells which were mostly Calretinin-positive. Calretinin mRNA was particularly abundant in the parvocellular reticular nucleus. Most Calretinin-immunoreactive cells also expressed at least one of the glutamate receptor subtypes examined with the exception of the smallest Calretinin-positive cells of the parvocellular reticular formation which were generally not immunoreactive for any of the glutamate receptors examined. Calretinin immunoreactivity was colocalized with immunoreactivity for all three glutamate receptor subtypes examined in most of the large cells of the reticular formation. Immunoreactivity for the GluR4 antibody was least abundant in the reticular formation and GluR4 immunoreactive cells were least likely to co-express Calretinin. These results suggest that Calretinin and glutamate receptor antibodies may be used to identify specific subsets of reticular formation neurons.
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Expression and rapid purification of recombinant rat Calretinin: similarity to native rat Calretinin.
Protein Expression and Purification, 1994Co-Authors: Kenneth I. Strauss, Lois Winsky, J. Kuznicki, David M JacobowitzAbstract:Rat Calretinin coding region was subcloned into a prokaryotic expression vector (pGEX). The glutathione-S-transferase:Calretinin fusion protein produced in Escherichia coli was purified on a glutathione-Sepharose affinity column. Recombinant rat Calretinin was cleaved on the column by thrombin, eluted, and purified to homogeneity using DEAE-cellulose chromatography. Recombinant and native rat Calretinin performed the same on DEAE columns, denaturing polyacrylamide gel electrophoresis (SDS-PAGE), Western blots, and 45Ca overlay on nitrocellulose blots. The recombinant Calretinin migrated similarly to the more basic (pI 5.3) of two forms of native Calretinin demonstrated by two-dimensional SDS-PAGE. Calcium binding equilibria revealed identical apparent binding affinity and capacity. Difference(s) between native and recombinant did not affect the binding of calcium to Calretinin or antibody recognition. Thus recombinant Calretinin may be useful in the elucidation of possible cellular targets of native Calretinin.
Robert J Kurman - One of the best experts on this subject based on the ideXlab platform.
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Calretinin a more sensitive but less specific marker than α inhibin for ovarian sex cord stromal neoplasms an immunohistochemical study of 215 cases
The American Journal of Surgical Pathology, 2002Co-Authors: Saeid Movahedilankarani, Robert J KurmanAbstract:Although inhibin has been shown to be a sensitive marker for ovarian sex cord-stromal and fibrous neoplasms, it may be negative in some cases. Calretinin, a mesothelial marker, has shown promise as a marker for sex cord-stromal neoplasms. The aim of this study was to evaluate and compare Calretinin and inhibin as immunohistochemical markers for sex cord-stromal and fibrous neoplasms. A total of 215 ovarian neoplasms were immunostained with commercially available antibodies to Calretinin and inhibin. These tumors included 87 sex cord-stromal (39 granulosa cell, 13 Sertoli-Leydig, 4 Sertoli, 9 thecomas, 14 fibrothecomas, and 8 other stromal tumors), 37 fibrous (20 fibromas, 9 adenofibromas, and 8 fibrosarcomas), 65 epithelial, 22 germ cell, and 4 miscellaneous neoplasms. The staining was evaluated on a 0-4 scale based on percentage of neoplastic cells labeling: 0 = none; 1+ = 1-25%; 2+ = 26-50%; 3+ = 51-75%; 4+ = 76-100%. Calretinin reactivity was detected in 100% of sex cord-stromal and 90% of fibrous neoplasms, including 32 that were inhibin negative (2 granulosa cell tumors, 1 Sertoli-Leydig cell tumor, 1 thecoma, 3 fibrothecomas, 16 fibromas, 6 adenofibromas, and 3 fibrosarcomas). All four Calretinin-negative fibrous neoplasms were inhibin negative. Calretinin staining was also detected in 22% of epithelial neoplasms but none of the germ cell and miscellaneous neoplasms tested. Inhibin staining was detected in 92% of sex cord-stromal neoplasms, 22% of fibrous neoplasms, 2% of epithelial neoplasms, and none of the germ cell and miscellaneous neoplasms tested. Calretinin has a 97% sensitivity and 85% specificity for sex cord-stromal and fibrous neoplasms, whereas inhibin has a 71% sensitivity and 99% specificity. This study shows that both Calretinin and inhibin are useful in the diagnosis of ovarian sex cord-stromal and fibrous neoplasms. Calretinin is a more sensitive but less specific immunohistochemical marker than inhibin. Calretinin is particularly useful in the diagnosis of sex cord-stromal and fibrous neoplasms that are inhibin negative. The high frequency of Calretinin in fibrous neoplasms suggests that a subgroup of these neoplasms may be derived from specialized gonadal stromal cells, perhaps thecal cells.
Martina Storz - One of the best experts on this subject based on the ideXlab platform.
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d2 40 and Calretinin a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation
Modern Pathology, 2007Co-Authors: Marc Hinterberger, Tanja Reineke, Martina Storz, Walter Weder, Peter Vogt, Holger MochAbstract:Anti-Calretinin antibodies are useful to differentiate adenocarcinomas from malignant mesotheliomas of the lung. Therefore, Calretinin expression is rarely reported for sarcomatoid mesotheliomas. Anti-podoplanin antibodies (eg D2-40) react with lymphatic endothelia, Kaposi's sarcoma, lymphangioma and mesotheliomas. For the interpretation of spindle cell lesions of the pleura, knowledge of Calretinin and D2-40 expression frequencies in sarcomatoid mesothelioma is desirable. To systematically investigate the sensitivity of Calretinin and D2-40 antibodies in epithelioid and sarcomatoid areas of malignant mesotheliomas, a tissue microarray with 341 malignant mesotheliomas, including 112 epithelioid, 46 sarcomatoid and 183 biphasic tumors was constructed. Epithelioid and sarcomatoid differentiated tumor areas were clearly separated within the tissue microarray. Expression of Calretinin and D2-40 was separately studied in epithelioid and sarcomatoid areas by immunohistochemistry. Calretinin expression was found in 91% of epithelioid and 57% of sarcomatoid tumor areas. D2-40 immunostaining was present in 66% of the epithelioid and 30% of the sarcomatoid tumor areas. A combination of Calretinin and D2-40 increased the sensitivity in epithelioid tumor areas to 0.96 and in sarcomatoid tumor areas to 0.66. These data indicate that a combination of Calretinin and D2-40 will improve diagnostic accuracy for spindle cell lesions of the pleura, whereas almost all epithelioid mesotheliomas are identified by Calretinin alone.
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Calretinin expression in human normal and neoplastic tissues a tissue microarray analysis on 5233 tissue samples
Human Pathology, 2003Co-Authors: Alessandro Lugli, Martina Storz, Yvonne Forster, Philippe Haas, Antoinio Nocito, Christoph Bucher, Heidi Bissig, Martina Mirlacher, Michael J Mihatsch, Guido SauterAbstract:Calretinin is a calcium-binding protein expressed in different normal and neoplastic tissues. Early studies suggested that Calretinin is a useful marker to differentiate adenocarcinomas from malignant mesotheliomas of the lung, but subsequent work has shown that Calretinin can be expressed in several other tumor types. To systematically investigate the epidemiology of Calretinin expression in normal and neoplastic tissues, we used tissue microarrays (TMAs) to analyze the immunohistochemically detectable expression of Calretinin in 5233 tissue samples from 128 different tumor categories and 76 different normal tissue types. At least 1 case with weak expression could be found in 74 of 128 (58%) different tumor types and 46 entities (36%) had at least 1 tumor with strong positivity. In normal tissues, a particularly strong expression was found in Leydig cells of the testis, neurons of the brain, theca-lutein and theca interna cells of the ovary, and mesothelium. In tumors, strong Calretinin expression was most frequently found in malignant mesotheliomas (6 of 7), Leydig cell tumors of the testis (5 of 5), adenomas of adrenal gland (5 of 9), and adenomatoid tumors (4 of 9). In summary, Calretinin is frequently expressed in many different tumor types. Metastases of various different origins must be included in the differential diagnosis of Calretinin-positive pleura tumors.
