The Experts below are selected from a list of 4491 Experts worldwide ranked by ideXlab platform
Andrew T. Parsa - One of the best experts on this subject based on the ideXlab platform.
-
sarcoma arising as a distinct nodule within glioblastoma a morphological and molecular perspective on Gliosarcoma
Journal of Neuro-oncology, 2011Co-Authors: Cynthia A Jimenez, Jill M Hagenkord, Martin P Powers, Andrew T. Parsa, Christine M Glastonbury, Tarik TihanAbstract:Gliosarcoma is a variant of glioblastoma and is characterized by distinct glial and sarcomatous components. Typically, there is no macroscopic boundary between the components and special stains are often required to distinguish the glial and sarcomatous elements. Some studies suggest similar genetic alterations in both components pointing to a common origin. We present an extreme case of Gliosarcoma arising as a discrete fibrous nodule adjacent to a typical glioblastoma. A 65 year-old woman presented with progressive weakness, seizures and right-sided hemiparesis. CT scan demonstrated an irregular enhancing left frontal lobe mass and an adjacent discrete nodule with different imaging characteristics. The unique nature of this macroscopically biphasic neoplasm allowed us to compare the molecular characteristics of glial and sarcomatous elements which were strikingly similar except for small losses and gains in Chr 3. Studies are under way to determine the significance of chromosome 3 alterations in Gliosarcomas.
-
clinical characteristics and outcomes for a modern series of primary Gliosarcoma patients
Cancer, 2010Co-Authors: Seunggu J. Han, Michael D Prados, Isaac Yang, Tarik Tihan, Brian J Ahn, Jose Otero, Michael W Mcdermott, Mitchel S Berger, Andrew T. ParsaAbstract:BACKGROUND: Primary Gliosarcoma (PGS) is a rare central nervous system tumor with limited experience reported in the literature. In the current study, the authors present a modern series of confirmed PGS cases treated in the era of magnetic resonance imaging (MRI), after the accepted glioblastoma management of resection, radiation, and temozolomide. METHODS: Using a retrospective review, patients with confirmed PGS were identified (1996-2008). Cases were determined to be PGS by central pathology review using the 2007 World Health Organization criteria. Extensive chart review was performed to gather clinical and pathologic data on these cases. RESULTS: All but 1 patient had undergone a preoperative MRI, with 1 patient receiving a computed tomography scan due to a cardiac pacemaker. A total of 10 patients received radiotherapy with concurrent and adjuvant temozolomide chemotherapy, and 8 patients received radiotherapy alone or in combination with other chemotherapeutic agents. In 2 patients, the history of adjuvant treatment could not be confirmed. The overall median survival was 13.9 months (range, 2.2-22.9 months). Patients with Gliosarcomas resembling meningioma were found to have a significantly prolonged median survival compared with patients harboring Gliosarcoma resembling glioblastoma multiforme (16 months vs 9.6 months; P = .011). However, no difference in survival was noted between patients who received concurrent radiotherapy and temozolomide compared with those who did not (10.4 months vs 13.9 months; P = .946). CONCLUSIONS: The results of the current study support previous hypotheses that there are 2 distinct types of PGS. The type mimicking the appearance of a meningioma appears to carry a significantly more favorable prognosis, most likely due to an increased chance at achieving macroscopic total resection. Cancer 2010. © 2010 American Cancer Society.
-
Primary Gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity
Journal of Neuro-Oncology, 2010Co-Authors: Seunggu J. Han, Michael D Prados, Isaac Yang, Tarik Tihan, Andrew T. ParsaAbstract:This report presents the historical experience, clinical presentation, treatment, prognosis, and pathogenesis of Gliosarcoma described to date in the English literature. PubMed query of term “Gliosarcoma” was performed, followed by a rigorous review of cited literature. Articles selected for analysis included: (1) case reports of Gliosarcoma, (2) review articles of Gliosarcoma, and (3) studies of the pathogenesis or genetics of Gliosarcoma in humans. Our review identified 219 cases of Gliosarcoma in 34 reports and eight articles addressing the pathogenesis. Survival in larger series ranged 4–11.5 months. Features unique to Gliosarcoma compared to glioblastoma (GBM) include their temporal lobe predilection, potential to appear similar to a meningioma at surgery, repeated reports of extracranial metastases, and infrequency of EGFR mutations. Published experience is limited to small case series, and the pathogenesis remains unclear. Clinical and pathologic characteristics distinct from GBM suggest that they may warrant specific treatment, separate from conventional GBM therapy.
-
Secondary Gliosarcoma: a review of clinical features and pathological diagnosis.
Journal of neurosurgery, 2010Co-Authors: Seunggu J. Han, Isaac Yang, Tarik Tihan, Susan M. Chang, Andrew T. ParsaAbstract:Object Although secondary Gliosarcoma after treatment of primary glioblastoma multiforme has been described, little is known of these rare tumors. In this article the authors review the literature on secondary Gliosarcoma, with attention to clinical course and pathological features. Methods A PubMed search of the key word intracranial “Gliosarcoma” with and without “radiation” or “radiotherapy” in humans was performed. The 204 citations yielded were screened for relevancy to Gliosarcomas that occur after treatment of previous intracranial neoplasms. Results A search of the literature yielded 24 relevant articles, combined for a total of only 12 cases of secondary Gliosarcoma and 12 cases of radiation-induced Gliosarcoma. Of the 12 cases of secondary Gliosarcoma, all were previously treated with surgery and radiotherapy (mean dose 50.7 Gy), with a mean survival of 13 months since time of Gliosarcoma diagnosis (range 6.9–19.4 months). In the cases of radiation-induced Gliosarcoma, the mean dose of previous ...
-
Secondary Gliosarcoma after diagnosis of glioblastoma: clinical experience with 30 consecutive patients
Journal of neurosurgery, 2010Co-Authors: Seunggu J. Han, Isaac Yang, Tarik Tihan, Susan M. Chang, Brian J Ahn, Jose Otero, Michael W Mcdermott, Mitchel S Berger, Andrew T. ParsaAbstract:Object Gliosarcoma can arise secondarily, after conventional adjuvant treatment of high-grade glioma. The current literature on the occurrence of secondary Gliosarcoma (SGS) after glioblastoma multiforme (GBM) is limited, with only 12 reported cases. The authors present a large series of histologically confirmed SGSs, with follow-up to describe the clinical and radiological presentation, pathological diagnosis, and treatment outcomes. Methods Gliosarcoma cases were identified using the University of California, San Francisco's Departments of Neurological Surgery and Neuropathology databases. Through a retrospective chart review, cases of Gliosarcoma were considered SGS if the following inclusion criteria were met: 1) the patient had a previously diagnosed intracranial malignant glioma that did not have Gliosarcoma components; and 2) the histopathological tissue diagnosis of the recurrence confirmed Gliosarcoma according to the most current WHO criteria. Extensive review of clinical, surgical, and patholog...
Masaya Nagaishi - One of the best experts on this subject based on the ideXlab platform.
-
Gliosarcoma with ependymal and PNET-like differentiation.
Clinical neuropathology, 2013Co-Authors: Masayuki Shintaku, Masaya Nagaishi, Hiroyuki Yoneda, Junko Hirato, Hidetoshi OkabeAbstract:A rare case of Gliosarcoma which arose in the temporal lobe of a 39-yearold man was reported. The gliomatous area of the tumor showed ependymal differentiation, and also contained immature neuroectodermal tissue resembling a primitive neuroectodermal tumor (PNET) in addition to an ordinary glioblastomatous component. Tumor cells in the PNET-like component were immunoreactive for synaptophysin, CD99, neurogenin 3, and α-internexin, but not for glial fibrillary acidic protein (GFAP), Class III-β tubulin, or Neu N. The mesenchymal area exhibited a compact fascicular proliferation of atypical spindle cells invested by fine reticulin fibrils. In addition, these cells were immunoreactive for Slug and Twist - transcription factors which are involved in the "epithelial-mesenchymal transition (EMT)" phenomenon. Gliosarcomas containing an ependymal or PNET-like component are rare, and to our knowledge, the present case is the first to be reported whose glial element exhibited differentiation toward these two components. The diverse differentiation in the glial element suggests that the tumor most likely originated from primitive neuroepithelial progenitor cells rather than from the neometaplasia of a glioblastoma. The immunoreactivity for transcription factors in the mesenchymal element indicated that EMT might be involved in the pathogenesis of this very rare type of Gliosarcoma.
-
transcriptional factors for epithelial mesenchymal transition are associated with mesenchymal differentiation in Gliosarcoma
Brain Pathology, 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Hiroko OhgakiAbstract:Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in Gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 Gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) Gliosarcomas, but not in glial areas (P 50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) Gliosarcomas, but glial tumor areas were largely negative except in four cases (P 10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of Gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in Gliosarcomas.
-
Transcriptional Factors for Epithelial–Mesenchymal Transition Are Associated with Mesenchymal Differentiation in Gliosarcoma
Brain pathology (Zurich Switzerland), 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Hiroko OhgakiAbstract:Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in Gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 Gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) Gliosarcomas, but not in glial areas (P 50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) Gliosarcomas, but glial tumor areas were largely negative except in four cases (P 10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of Gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in Gliosarcomas.
-
Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in Gliosarcoma
American Journal of Pathology, 2012Co-Authors: Masaya Nagaishi, Benjamin Brokinkel, Felice Giangaspero, Y. H. Kim, M. Mittelbronn, W. Paulus, A. Vital, Y. Tanaka, Y. Nakazato, Catherine Legras-lachuerAbstract:Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas that display either glial (glial fibrillary acidic protein-positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses have shown identical genetic alterations in glial and mesenchymal tumor areas, suggesting that Gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array comparative genomic hybridization in glial and mesenchymal tumor areas of 13 Gliosarcomas. The patterns of gain and loss were similar, except that the gain at 13q13.3-q14.1 (log(2) ratio \\textgreater3.0), containing the STOML3, FREM2, and LHFP genes, which was restricted to the mesenchymal tumor area of a Gliosarcoma. Further analyses of 64 cases of Gliosarcoma using quantitative PCR showed amplification of the STOML3, FREM2, and LHFP genes in 14 (22%), 10 (16%), and 7 (11%) mesenchymal tumor areas, respectively, but not in glial tumor areas. Results of IHC analysis confirmed that overexpression of STOML3 and FREM2 was more extensive in mesenchymal than in glial tumor areas. These results suggest that the mesenchymal components in a small fraction of Gliosarcomas may be derived from glial cells with additional genetic alterations.
-
Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in Gliosarcoma.
The American journal of pathology, 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Y. H. Kim, M. Mittelbronn, Catherine Legras-lachuerAbstract:Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas that display either glial (glial fibrillary acidic protein–positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses have shown identical genetic alterations in glial and mesenchymal tumor areas, suggesting that Gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array comparative genomic hybridization in glial and mesenchymal tumor areas of 13 Gliosarcomas. The patterns of gain and loss were similar, except that the gain at 13q13.3-q14.1 (log 2 ratio >3.0), containing the STOML3 , FREM2 , and LHFP genes, which was restricted to the mesenchymal tumor area of a Gliosarcoma. Further analyses of 64 cases of Gliosarcoma using quantitative PCR showed amplification of the STOML3 , FREM2 , and LHFP genes in 14 (22%), 10 (16%), and 7 (11%) mesenchymal tumor areas, respectively, but not in glial tumor areas. Results of IHC analysis confirmed that overexpression of STOML3 and FREM2 was more extensive in mesenchymal than in glial tumor areas. These results suggest that the mesenchymal components in a small fraction of Gliosarcomas may be derived from glial cells with additional genetic alterations.
Felice Giangaspero - One of the best experts on this subject based on the ideXlab platform.
-
Clinical Study Gliosarcomas: analysis of 11 cases do two subtypes exist?
2015Co-Authors: Maurizio Salvati, Felice Giangaspero, Emanuela Caroli, Antonino Raco, Roberto Delfini, Luigi FerranteAbstract:There are conflicting reports regarding Gliosarcomas. The goal of this study is to examine clinical, radiological, surgical and therapeutic aspects of 11 patients with Gliosarcoma. Between 1993 and 2001, 11 patients with cerebral Gliosarcoma were treated at our Institute. Ten patients underwent surgery and one patient had stereotactic biopsy. Four patients received whole brain radiotherapy with 60Co, five underwent radiotherapy with LINAC extended 2 cm beyond the edema margins. One patient refused any additional treatment after surgery and one patient was not treated postoperatively for poor clinical conditions (KPS 40). Chemotherapy (temozolomide) was administered to four patients. Four patients had a prevalence of sarcomatous component that corresponded to surgical and radiological aspects similar to meningioma while six patients showed a prevalence of gliomatous component and radiological and surgical aspects similar to those of glioblastomas. Surgical resection was total in six and subtotal in four patients. Patients with prevalent sarcomatous component showed median survival time more prolonged than patients with prevalent gliomatous component (71 ± 6 weeks vs. 63 ± 6; P 0.0417). Moreover, the survival rate differed in relation to the therapy: patients treated with multimodality therapy (surgery, radiotherapy and chemotherapy) had a longer survival time than patients treated in single or bimodality. Despite prognosis of Gliosarcomas remains poor, a multidisciplinary approach (surgery, radiotherapy and chemotherapy) seems to be associated with slight more prolonged survival times
-
transcriptional factors for epithelial mesenchymal transition are associated with mesenchymal differentiation in Gliosarcoma
Brain Pathology, 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Hiroko OhgakiAbstract:Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in Gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 Gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) Gliosarcomas, but not in glial areas (P 50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) Gliosarcomas, but glial tumor areas were largely negative except in four cases (P 10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of Gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in Gliosarcomas.
-
Transcriptional Factors for Epithelial–Mesenchymal Transition Are Associated with Mesenchymal Differentiation in Gliosarcoma
Brain pathology (Zurich Switzerland), 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Hiroko OhgakiAbstract:Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in Gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 Gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) Gliosarcomas, but not in glial areas (P 50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) Gliosarcomas, but glial tumor areas were largely negative except in four cases (P 10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of Gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in Gliosarcomas.
-
Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in Gliosarcoma
American Journal of Pathology, 2012Co-Authors: Masaya Nagaishi, Benjamin Brokinkel, Felice Giangaspero, Y. H. Kim, M. Mittelbronn, W. Paulus, A. Vital, Y. Tanaka, Y. Nakazato, Catherine Legras-lachuerAbstract:Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas that display either glial (glial fibrillary acidic protein-positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses have shown identical genetic alterations in glial and mesenchymal tumor areas, suggesting that Gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array comparative genomic hybridization in glial and mesenchymal tumor areas of 13 Gliosarcomas. The patterns of gain and loss were similar, except that the gain at 13q13.3-q14.1 (log(2) ratio \\textgreater3.0), containing the STOML3, FREM2, and LHFP genes, which was restricted to the mesenchymal tumor area of a Gliosarcoma. Further analyses of 64 cases of Gliosarcoma using quantitative PCR showed amplification of the STOML3, FREM2, and LHFP genes in 14 (22%), 10 (16%), and 7 (11%) mesenchymal tumor areas, respectively, but not in glial tumor areas. Results of IHC analysis confirmed that overexpression of STOML3 and FREM2 was more extensive in mesenchymal than in glial tumor areas. These results suggest that the mesenchymal components in a small fraction of Gliosarcomas may be derived from glial cells with additional genetic alterations.
-
Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in Gliosarcoma.
The American journal of pathology, 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Y. H. Kim, M. Mittelbronn, Catherine Legras-lachuerAbstract:Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas that display either glial (glial fibrillary acidic protein–positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses have shown identical genetic alterations in glial and mesenchymal tumor areas, suggesting that Gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array comparative genomic hybridization in glial and mesenchymal tumor areas of 13 Gliosarcomas. The patterns of gain and loss were similar, except that the gain at 13q13.3-q14.1 (log 2 ratio >3.0), containing the STOML3 , FREM2 , and LHFP genes, which was restricted to the mesenchymal tumor area of a Gliosarcoma. Further analyses of 64 cases of Gliosarcoma using quantitative PCR showed amplification of the STOML3 , FREM2 , and LHFP genes in 14 (22%), 10 (16%), and 7 (11%) mesenchymal tumor areas, respectively, but not in glial tumor areas. Results of IHC analysis confirmed that overexpression of STOML3 and FREM2 was more extensive in mesenchymal than in glial tumor areas. These results suggest that the mesenchymal components in a small fraction of Gliosarcomas may be derived from glial cells with additional genetic alterations.
Catherine Legras-lachuer - One of the best experts on this subject based on the ideXlab platform.
-
Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in Gliosarcoma
American Journal of Pathology, 2012Co-Authors: Masaya Nagaishi, Benjamin Brokinkel, Felice Giangaspero, Y. H. Kim, M. Mittelbronn, W. Paulus, A. Vital, Y. Tanaka, Y. Nakazato, Catherine Legras-lachuerAbstract:Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas that display either glial (glial fibrillary acidic protein-positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses have shown identical genetic alterations in glial and mesenchymal tumor areas, suggesting that Gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array comparative genomic hybridization in glial and mesenchymal tumor areas of 13 Gliosarcomas. The patterns of gain and loss were similar, except that the gain at 13q13.3-q14.1 (log(2) ratio \\textgreater3.0), containing the STOML3, FREM2, and LHFP genes, which was restricted to the mesenchymal tumor area of a Gliosarcoma. Further analyses of 64 cases of Gliosarcoma using quantitative PCR showed amplification of the STOML3, FREM2, and LHFP genes in 14 (22%), 10 (16%), and 7 (11%) mesenchymal tumor areas, respectively, but not in glial tumor areas. Results of IHC analysis confirmed that overexpression of STOML3 and FREM2 was more extensive in mesenchymal than in glial tumor areas. These results suggest that the mesenchymal components in a small fraction of Gliosarcomas may be derived from glial cells with additional genetic alterations.
-
Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in Gliosarcoma.
The American journal of pathology, 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Y. H. Kim, M. Mittelbronn, Catherine Legras-lachuerAbstract:Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas that display either glial (glial fibrillary acidic protein–positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses have shown identical genetic alterations in glial and mesenchymal tumor areas, suggesting that Gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array comparative genomic hybridization in glial and mesenchymal tumor areas of 13 Gliosarcomas. The patterns of gain and loss were similar, except that the gain at 13q13.3-q14.1 (log 2 ratio >3.0), containing the STOML3 , FREM2 , and LHFP genes, which was restricted to the mesenchymal tumor area of a Gliosarcoma. Further analyses of 64 cases of Gliosarcoma using quantitative PCR showed amplification of the STOML3 , FREM2 , and LHFP genes in 14 (22%), 10 (16%), and 7 (11%) mesenchymal tumor areas, respectively, but not in glial tumor areas. Results of IHC analysis confirmed that overexpression of STOML3 and FREM2 was more extensive in mesenchymal than in glial tumor areas. These results suggest that the mesenchymal components in a small fraction of Gliosarcomas may be derived from glial cells with additional genetic alterations.
Werner Paulus - One of the best experts on this subject based on the ideXlab platform.
-
transcriptional factors for epithelial mesenchymal transition are associated with mesenchymal differentiation in Gliosarcoma
Brain Pathology, 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Hiroko OhgakiAbstract:Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in Gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 Gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) Gliosarcomas, but not in glial areas (P 50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) Gliosarcomas, but glial tumor areas were largely negative except in four cases (P 10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of Gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in Gliosarcomas.
-
Transcriptional Factors for Epithelial–Mesenchymal Transition Are Associated with Mesenchymal Differentiation in Gliosarcoma
Brain pathology (Zurich Switzerland), 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Hiroko OhgakiAbstract:Gliosarcoma is a rare variant of glioblastoma characterized by a biphasic pattern of glial and mesenchymal differentiation. It is unclear whether mesenchymal differentiation in Gliosarcomas is because of extensive genomic instability and/or to a mechanism similar to epithelial-mesenchymal transition (EMT). In the present study, we assessed 40 Gliosarcomas for immunoreactivity of Slug, Twist, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which are involved in EMT in epithelial tumors. Nuclear Slug expression was observed in >50% of neoplastic cells in mesenchymal tumor areas of 33 (83%) Gliosarcomas, but not in glial areas (P 50% of neoplastic cells in mesenchymal tumor areas of 35 (88%) Gliosarcomas, but glial tumor areas were largely negative except in four cases (P 10% neoplastic cells. Thus, expression of Slug, Twist, MMP-2 and MMP-9 was characteristic of mesenchymal tumor areas of Gliosarcomas, suggesting that mechanisms involved in the EMT in epithelial neoplasms may play roles in mesenchymal differentiation in Gliosarcomas.
-
Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in Gliosarcoma.
The American journal of pathology, 2012Co-Authors: Masaya Nagaishi, Werner Paulus, Benjamin Brokinkel, Anne Vital, Yuko Tanaka, Yoichi Nakazato, Felice Giangaspero, Y. H. Kim, M. Mittelbronn, Catherine Legras-lachuerAbstract:Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas that display either glial (glial fibrillary acidic protein–positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses have shown identical genetic alterations in glial and mesenchymal tumor areas, suggesting that Gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array comparative genomic hybridization in glial and mesenchymal tumor areas of 13 Gliosarcomas. The patterns of gain and loss were similar, except that the gain at 13q13.3-q14.1 (log 2 ratio >3.0), containing the STOML3 , FREM2 , and LHFP genes, which was restricted to the mesenchymal tumor area of a Gliosarcoma. Further analyses of 64 cases of Gliosarcoma using quantitative PCR showed amplification of the STOML3 , FREM2 , and LHFP genes in 14 (22%), 10 (16%), and 7 (11%) mesenchymal tumor areas, respectively, but not in glial tumor areas. Results of IHC analysis confirmed that overexpression of STOML3 and FREM2 was more extensive in mesenchymal than in glial tumor areas. These results suggest that the mesenchymal components in a small fraction of Gliosarcomas may be derived from glial cells with additional genetic alterations.
-
Interphase cytogenetics of glioblastoma and Gliosarcoma
Acta neuropathologica, 1994Co-Authors: Werner Paulus, Antonios Bayas, German Ott, Wolfgang RoggendorfAbstract:Interphase cytogenetics, i.e., in situ hybridization using probes to chromosome-specific DNA, enables histological identification of cells bearing numerical chromosome aberrations and cytogenetic analysis of composite tumors. We studied routinely processed tissues from seven glioblastomas and three Gliosarcomas using biotinylated probes to pericentromeric alpha-satellite sequences on chromosomes 10, 17 and X. By applying various pretreatment protocols, an evaluable compromise between morphology and signal intensity was obtained in most cases. Compared to vascular cells with normal chromosomal counts, a significant subpopulation of glioblastoma cells showed monosomy 10 (four of five cases), monosomy 17 (one of seven cases) and loss of one X chromosome (one of seven cases). All monosomy 10 cases comprised additional areas where two copies of chromosome 10 were retained. Among the Gliosarcomas, both the glioma and the sarcoma portion showed monosomy 10 in one case and monosomy 17 in another case. In contrast, in the third case of Gliosarcoma, monosomy 10 was found only in the glioma portion, whereas a gain of chromosome X was observed in the sarcoma portion. We conclude that: (1) numerical chromosome aberrations can be detected in routinely processed brain tumor biopsy specimens using interphase cytogenetics, making retrospective studies feasiblel (2) glioblastomas show intratumoral cytogenetic heterogeneity with formation of monoclonal cell clusters; and (3) sarcoma and glioma elements in Gliosarcomas may exhibit the same or different numerical chromosome aberrations, suggesting various histogenetic pathways of the sarcoma-like portion.