Vani Santosh

Publications of Vani Santosh

• De novo gliosarcoma occurring in the posterior fossa of a 11-year-old girl.

  Authors: Chikkannaiah Panduranga, Dawn Bharath, Somanna Sampath, Vani Santosh

  Clinical neuropathology. 04/2012;

• Intramedullary metastasis in a case of vermian medulloblastoma.

  Authors: Venkatesh S Madhugiri, Paritosh Pandey, B Indira Devi, Vani Santosh, T C Yasha

  British journal of neurosurgery. 10/2011;

  Abstract Medulloblastoma is one of the commonest primary CNS malignancies in children. Leptomeningeal dissemination and distant metastasis have been associated with medulloblastoma, butAbstract Medulloblastoma is one of the commonest primary CNS malignancies in children. Leptomeningeal dissemination and distant metastasis have been associated with medulloblastoma, but intramedullary metastases are very rare. CSF cytology and contrast-enhanced MRI are the main modalities used to diagnose leptomeningeal dissemination. However, intramedullary metastases are best picked up with contrast-enhanced axial sequences on MR imaging. In this report, a patient with medulloblastoma who developed intramedullary metastasis is described. The role of imaging and CSF cytology in diagnosing the spread along the CSF pathways is reviewed. Allusions are made to the possible mechanism of intramedullary metastasis in these tumors.

• Primary myxopapillary ependymoma of the fourth ventricle with cartilaginous metaplasia: a case report and review of the literature.

  Authors: Shrijeet Chakraborti, Aparna Govindan, Jacob P Alapatt, M Radhakrishnan, Vani Santosh

  Brain tumor pathology. 08/2011; 29(1):25-30.

  Myxopapillary ependymoma (MPE), which is a benign histological subtype of ependymoma, is found predominantly in the cauda equina region. It occurs rarely in the brain and mostly as a metastaticMyxopapillary ependymoma (MPE), which is a benign histological subtype of ependymoma, is found predominantly in the cauda equina region. It occurs rarely in the brain and mostly as a metastatic deposit from a spinal lesion. The occurrence of primary intracranial MPE is exceptional, with only 11 cases reported to date. We report an additional case of intracranial MPE, which is the third reported case in the fourth ventricle. The tumor manifested in a 50-year-old lady, who presented with features of raised intracranial pressure. A gross total resection of the tumor was achieved. Histologically, the tumor had characteristic features of MPE with focal metaplastic cartilaginous deposit. On further evaluation, there was no evidence of a primary tumor in the spinal cord. Intracranial MPE needs further evaluation by craniospinal MRI to exclude an unrecognized primary in the spinal region, which could warrant surgical attention.

• Histopathologic and immunohistochemical profile of spinal glioblastoma: a study of six cases.

  Authors: Aparna Govindan, Shrijeet Chakraborti, Anita Mahadevan, Yasha T Chickabasavaiah, Vani Santosh, S K Shankar

  Brain tumor pathology. 06/2011; 28(4):297-303.

  Spinal intramedullary glioblastomas are uncommon tumors and are known to have a very poor prognosis. Only a few studies in the literature have described their histopathological characteristics. WeSpinal intramedullary glioblastomas are uncommon tumors and are known to have a very poor prognosis. Only a few studies in the literature have described their histopathological characteristics. We describe the detailed histopathological and immunohistochemical profiles of six cases of spinal glioblastoma. Most of the tumors were located in the cervical or cervicothoracic region. The majority of the patients were young adults (mean age 34.8 years), presenting with a short duration of symptoms of 2 months or less. Their histopathological features were similar to cerebral glioblastoma. Diverse vascular changes like microvascular proliferation, sprouting angiogenesis, sclerosed and thrombosed vessels, along with field necrosis were prominent findings. All tumors were positive for GFAP and negative for EMA. The MIB-1 labeling index was very high (mean 16.7 ± 3.2%). Five out of six tumors were immunoreactive for p53 protein, and only two showed over-expression of EGFR protein. The predominant expression of p53 in these young patients suggests that spinal glioblastomas are similar to secondary glioblastoma in the cerebral hemispheres, despite the short duration of symptoms in them and vascular changes that are similar to those noted in primary glioblastoma. These observations support the fact that spinal glioblastomas are heterogeneous tumors underlined by complex molecular pathways. Nevertheless, inactivation of the p53 tumor suppressor pathway could play a major role in the genesis of these neoplasms.

• Insulin growth factor-2 binding protein 3 (IGF2BP3) is a glioblastoma-specific marker that activates phosphatidylinositol 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) pathways by modulating IGF-2.

  Authors: Ramaswamy Suvasini, Bhargava Shruti, Balaram Thota, Sridevi Vijay Shinde, Dinorah Friedmann-Morvinski, Zahid Nawaz, Krishnarao Venkatesh Prasanna, Kandavel Thennarasu, Alangar Sathyaranjandas Hegde, Arimappamagan Arivazhagan, Bangalore Ashwathnarayanarao Chandramouli, Vani Santosh, Kumaravel Somasundaram

  The Journal of biological chemistry. 05/2011; 286(29):25882-90.

  Glioblastoma is the most common and malignant form of primary astrocytoma. Upon investigation of the insulin-like growth factor (IGF) pathway, we found the IGF2BP3/IMP3 transcript and protein to beGlioblastoma is the most common and malignant form of primary astrocytoma. Upon investigation of the insulin-like growth factor (IGF) pathway, we found the IGF2BP3/IMP3 transcript and protein to be up-regulated in GBMs but not in lower grade astrocytomas (p < 0.0001). IMP3 is an RNA binding protein known to bind to the 5'-untranslated region of IGF-2 mRNA, thereby activating its translation. Overexpression- and knockdown-based studies establish a role for IMP3 in promoting proliferation, anchorage-independent growth, invasion, and chemoresistance. IMP3 overexpressing B16F10 cells also showed increased tumor growth, angiogenesis, and metastasis, resulting in poor survival in a mouse model. Additionally, the infiltrating front, perivascular, and subpial regions in a majority of the GBMs stained positive for IMP3. Furthermore, two different murine glioma models were used to substantiate the above findings. In agreement with the translation activation functions of IMP3, we also found increased IGF-2 protein in the GBM tumor samples without a corresponding increase in its transcript levels. Also, in vitro IMP3 overexpression/knockdown modulated the IGF-2 protein levels without altering its transcript levels. Additionally, IGF-2 neutralization and supplementation studies established that the proproliferative effects of IMP3 were indeed mediated through IGF-2. Concordantly, PI3K and MAPK, the downstream effectors of IGF-2, are activated by IMP3 and are found to be essential for IMP3-induced cell proliferation. Thus, we have identified IMP3 as a GBM-specific proproliferative and proinvasive marker acting through IGF-2 resulting in the activation of oncogenic PI3K and MAPK pathways.

• Supratentorial and cerebellar liponeurocytomas: report of four cases with review of literature.

  Authors: Shrijeet Chakraborti, Anita Mahadevan, Aparna Govindan, T C Yasha, Vani Santosh, Jerry M E Kovoor, Ravi Ramamurthi, Jacob P Alapatt, T Hedge, S K Shankar

  Journal of neuro-oncology. 05/2011; 103(1):121-7.

  Liponeurocytoma is not exclusive to the cerebellar or fourth ventricular location. Since its inclusion in the central nervous system tumor classification in 2000, six cases with similar radiological,Liponeurocytoma is not exclusive to the cerebellar or fourth ventricular location. Since its inclusion in the central nervous system tumor classification in 2000, six cases with similar radiological, histomorphological and immunohistochemical features have also been described in the lateral ventricles. In the present study, we report clinical, radiological and pathological findings of three supratentorial and one cerebellar liponeurocytoma from our records, evaluated with an extensive panel of immunohistochemistry, and review published cases in the literature. The immunohistochemical pattern of supratentorial and infratentorial liponeurocytomas are almost identical, which indicates that these tumors are homologous.

• Metachronous occurrence of a temporal ganglioglioma and a bifrontal anaplastic ependymoma: coincidence or an explainable pathological curiosity?

  Authors: Sumit Thakar, Vani Santosh, Nandita Ghosal, Sunil V Furtado, Alangar S Hegde

  British journal of neurosurgery. 04/2011; 25(6):741-3.

  In this first-of-its-kind report, we describe an unusual case of a 32-year-old man who harboured two biologically distinct metachronous brain tumours. He presented with features of raisedIn this first-of-its-kind report, we describe an unusual case of a 32-year-old man who harboured two biologically distinct metachronous brain tumours. He presented with features of raised intracranial pressure 8 years after total excision of a right temporal ganglioglioma. Imaging showed a heterogenously contrast enhancing bifrontal lesion with ventricular extension. Histopathological examination revealed an anaplastic ependymoma. While a co-incidental occurrence is a possibility, there could be possible mechanisms to explain this pathological oddity.

• Homozygous 10q23/PTEN deletion and its impact on outcome in glioblastoma: a prospective translational study on a uniformly treated cohort of adult patients.

  Authors: Mallavarapu R Srividya, Balaram Thota, Bangalore C Shailaja, Arimappamagan Arivazhagan, Kandavel Thennarasu, Bangalore A Chandramouli, Alangar S Hegde, Vani Santosh

  Neuropathology : official journal of the Japanese Society of Neuropathology. 12/2010; 31(4):376-83.

  Tumors from a prospective cohort of adult patients with newly diagnosed glioblastoma (n=73), treated uniformly with radiochemotherapy, were examined for 10q23/PTEN deletion by fluorescence in situTumors from a prospective cohort of adult patients with newly diagnosed glioblastoma (n=73), treated uniformly with radiochemotherapy, were examined for 10q23/PTEN deletion by fluorescence in situ hybridization (FISH). Statistical methods were employed to evaluate the degree of association between 10q23/PTEN deletion status and patient age. Survival analysis was performed using Kaplan-Meier log-rank test and multivariable Cox models to assess the prognostic value of 10q23/PTEN deletion. Interestingly, 10q23/PTEN homozygous deletion was frequent in patients >45 years of age (P=0.034) and the median age of patients harboring PTEN homozygous deletions was significantly higher than those with the retained status (P=0.019). 10q23/PTEN homozygous deletion was associated with shorter survival in the entire cohort as well in patients >45 years (P<0.05), indicating that loss of 10q23/PTEN showed clinical importance in elderly patients. Our study highlights the independent prognostic/predictive value of 10q23/PTEN deletion status as identified by FISH, particularly in glioblastoma patients aged >45 years.

• Proteomic identification of haptoglobin α2 as a glioblastoma serum biomarker: implications in cancer cell migration and tumor growth.

  Authors: Durairaj Mohan Kumar, Balaram Thota, Sridevi Vijay Shinde, K V Prasanna, A S Hegde, A Arivazhagan, B A Chandramouli, Vani Santosh, Kumaravel Somasundaram

  Journal of proteome research. 11/2010; 9(11):5557-67.

  Glioblastoma (GBM; grade IV astrocytoma) is the most malignant and common primary brain tumor in adults. Using combination of 2-DE and MALDI-TOF MS, we analyzed 14 GBM and 6 normal control sera andGlioblastoma (GBM; grade IV astrocytoma) is the most malignant and common primary brain tumor in adults. Using combination of 2-DE and MALDI-TOF MS, we analyzed 14 GBM and 6 normal control sera and identified haptoglobin α2 chain as an up-regulated serum protein in GBM patients. GBM-specific up-regulation was confirmed by ELISA based quantitation of haptoglobin (Hp) in the serum of 99 GBM patients as against lower grades (49 grade III/AA; 26 grade II/DA) and 26 normal individuals (p = 0.0001). Further validation using RT-qPCR on an independent set (n = 78) of tumor and normal brain (n = 4) samples and immunohistochemcial staining on a subset (n = 42) of above samples showed increasing levels of transcript and protein with tumor grade and were highest in GBM (p = <0.0001 and <0.0001, respectively). Overexpression of Hp either by stable integration of Hp cDNA or exogenous addition of purified Hp to immortalized astrocytes resulted in increased cell migration. RNAi-mediated silencing of Hp in glioma cells decreased cell migration. Further, we demonstrate that both human glioma and mouse melanoma cells overexpressing Hp showed increased tumor growth. Thus, we have identified haptoglobin as a GBM-specific serum marker with a role on glioma tumor growth and migration.

• Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma.

  Authors: Soumya A M Rao, Vani Santosh, Kumaravel Somasundaram

  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 10/2010; 23(10):1404-17.

  Malignant astrocytoma includes anaplastic astrocytoma (grade III) and glioblastoma (grade IV). Among them, glioblastoma is the most common primary brain tumor with dismal responses to all therapeuticMalignant astrocytoma includes anaplastic astrocytoma (grade III) and glioblastoma (grade IV). Among them, glioblastoma is the most common primary brain tumor with dismal responses to all therapeutic modalities. We performed a large-scale, genome-wide microRNA (miRNA) (n=756) expression profiling of 26 glioblastoma, 13 anaplastic astrocytoma and 7 normal brain samples with an aim to find deregulated miRNA in malignant astrocytoma. We identified several differentially regulated miRNAs between these groups, which could differentiate glioma grades and normal brain as recognized by PCA. More importantly, we identified a most discriminatory 23-miRNA expression signature, by using PAM, which precisely distinguished glioblastoma from anaplastic astrocytoma with an accuracy of 95%. The differential expression pattern of nine miRNAs was further validated by real-time RT-PCR on an independent set of malignant astrocytomas (n=72) and normal samples (n=7). Inhibition of two glioblastoma-upregulated miRNAs (miR-21 and miR-23a) and exogenous overexpression of two glioblastoma-downregulated miRNAs (miR-218 and miR-219-5p) resulted in reduced soft agar colony formation but showed varying effects on cell proliferation and chemosensitivity. Thus we have identified the miRNA expression signature for malignant astrocytoma, in particular glioblastoma, and showed the miRNA involvement and their importance in astrocytoma development.

• Glioblastoma-specific protein interaction network identifies PP1A and CSK21 as connecting molecules between cell cycle-associated genes.

  Authors: Jayashree Ladha, Sainitin Donakonda, Shipra Agrawal, Balaram Thota, Mallavarapu R Srividya, Sambandam Sridevi, Arimappamagan Arivazhagan, Kandavel Thennarasu, Anandh Balasubramaniam, Bangalore A Chandramouli, Alangar Sattiyaranjandas Hegde, Paturu Kondaiah, Kumaravel Somasundaram, Vani Santosh, Satyanarayana M R Rao

  Cancer research. 08/2010; 70(16):6437-47.

  Glioblastoma (GBM; grade IV astrocytoma) is a very aggressive form of brain cancer with a poor survival and few qualified predictive markers. This study integrates experimentally validated genes thatGlioblastoma (GBM; grade IV astrocytoma) is a very aggressive form of brain cancer with a poor survival and few qualified predictive markers. This study integrates experimentally validated genes that showed specific upregulation in GBM along with their protein-protein interaction information. A system level analysis was used to construct GBM-specific network. Computation of topological parameters of networks showed scale-free pattern and hierarchical organization. From the large network involving 1,447 proteins, we synthesized subnetworks and annotated them with highly enriched biological processes. A careful dissection of the functional modules, important nodes, and their connections identified two novel intermediary molecules CSK21 and protein phosphatase 1 alpha (PP1A) connecting the two subnetworks CDC2-PTEN-TOP2A-CAV1-P53 and CDC2-CAV1-RB-P53-PTEN, respectively. Real-time quantitative reverse transcription-PCR analysis revealed CSK21 to be moderately upregulated and PP1A to be overexpressed by 20-fold in GBM tumor samples. Immunohistochemical staining revealed nuclear expression of PP1A only in GBM samples. Thus, CSK21 and PP1A, whose functions are intimately associated with cell cycle regulation, might play key role in gliomagenesis.

• Identification of potential serum biomarkers of glioblastoma: serum osteopontin levels correlate with poor prognosis.

  Authors: Peddagangannagari Sreekanthreddy, Harish Srinivasan, Durairaj Mohan Kumar, Mamatha Bangalore Nijaguna, Sambandam Sridevi, Marigowda Vrinda, Arimappamagan Arivazhagan, Anandh Balasubramaniam, Alangar Sathyaranjandas Hegde, Bangalore A Chandramouli, Vani Santosh, Manchanahalli R S Rao, Paturu Kondaiah, Kumaravel Somasundaram

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 06/2010; 19(6):1409-22.

  The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM). Our previous glioma microarray database was mined toThe aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM). Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients. Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two downregulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis. Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs. Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis.

• Recurrence in medulloblastoma - influence of clinical, histological and immunohistochemical factors.

  Authors: Umesh Srikantha, Anandh Balasubramaniam, Vani Santosh, Sampath Somanna, Indira Devi Bhagavatula, Chandramouli Bangalore Ashwathnarayana

  British journal of neurosurgery. 06/2010; 24(3):280-8.

  The therapy for medulloblastomas has gone through several changes over the years. Research has shown that patients with medulloblastoma cannot be satisfactorily stratified into risk groups based onThe therapy for medulloblastomas has gone through several changes over the years. Research has shown that patients with medulloblastoma cannot be satisfactorily stratified into risk groups based on clinical and therapeutic factors alone. To study the clinical, histological features and expression of immunohistochemical markers in medulloblastoma, and to correlate these features with recurrence rates. Sixty-three cases of medulloblastomas operated at our institute from 1996-2003 were selected and retrospectively analyzed for therapy received, histological features and immunohistochemical expression of GFAP, synaptophysin, erb B2, p53, Bcl-2 and Trk-C along with assessment of MIB-1 labeling index(LI). The mean age of the 63 cases at presentation was 11.6 yrs. Near/Gross- total resection was achieved in 74.6% (47/63) of the cases. We propose a clinical-histological-immunohistochemical' model for medulloblastoma where extent of resection, administration of chemotherapy, presence of gross anaplasia and c-erb B2 overexpression status are the most important predictors of recurrence rates.

• Grade-specific expression of insulin-like growth factor-binding proteins-2, -3, and -5 in astrocytomas: IGFBP-3 emerges as a strong predictor of survival in patients with newly diagnosed glioblastoma.

  Authors: Vani Santosh, Arimappamagan Arivazhagan, Peddagangannagari Sreekanthreddy, Harish Srinivasan, Balaram Thota, Mallavarapu R Srividya, Marigowda Vrinda, Sambandam Sridevi, Bangalore C Shailaja, Cini Samuel, Krishnarao V Prasanna, Kandavel Thennarasu, Anandh Balasubramaniam, Bangalore A Chandramouli, Alangar S Hegde, Kumaravel Somasundaram, Paturu Kondaiah, Manchanahalli R S Rao

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 06/2010; 19(6):1399-408.

  Insulin-like growth factor (IGF)-binding protein (IGFBP) isoforms have been implicated in the pathogenesis of human neoplasms including glioma. In view of this, we evaluated the expression of IGFBPInsulin-like growth factor (IGF)-binding protein (IGFBP) isoforms have been implicated in the pathogenesis of human neoplasms including glioma. In view of this, we evaluated the expression of IGFBP isoforms (IGFBP-2, -3, and -5) during malignant progression of astrocytoma and their prognostic significance in glioblastoma. The expression of IGFBP isoforms was analyzed in diffusely infiltrating astrocytomas by real-time quantitative PCR (n = 203) and immunohistochemistry (n = 256). Statistical methods were used to assess their grade-specific expression pattern and mRNA-protein intercorrelation. Survival analyses were done on a uniformly treated, prospective cohort of adult patients with newly diagnosed glioblastoma (n = 136) by using Cox regression models. The mean transcript levels of IGFBP-2 and -3 were significantly higher in glioblastomas (GBM) relative to anaplastic astrocytoma (AA), diffuse astrocytoma (DA), and controls whereas IGFBP-5 mRNA was higher in GBM relative to AA and controls (P < 0.05). By immunohistochemistry, the mean labeling index of all isoforms was significantly higher in GBM compared with AA, DA, and control (P < 0.05). A strong positive correlation was observed between their respective mRNA and protein expressions (P < 0.01). Multivariate analysis revealed IGFBP-3 expression (hazard ratio, 1.021; P = 0.030) and patient age (hazard ratio, 1.027; P = 0.007) to be associated with shorter survival in glioblastoma. This study shows the associations of IGFBP-2, -3, and -5 expression with increasing grades of malignancy in astrocytomas. IGFBP-3 is identified as a novel prognostic glioblastoma biomarker. The strong correlation between their mRNA and protein expression patterns suggests their role in the pathogenesis of these tumors. IGFBP isoforms have emerged as biomarkers with diagnostic and prognostic utility in astrocytomas.

• Infectious lesions mimicking central nervous system neoplasms.

  Authors: Vani Santosh, Anita Mahadevan, Yasha T Chickabasaviah, Rose Dawn Bharath, Shankar S Krishna

  Seminars in diagnostic pathology. 05/2010; 27(2):122-35.

  Infections of the central nervous system (CNS) presenting as space-occupying lesions are not uncommon, particularly in developing countries. Most often, infective organisms gain entry into the CNSInfections of the central nervous system (CNS) presenting as space-occupying lesions are not uncommon, particularly in developing countries. Most often, infective organisms gain entry into the CNS through the hematogenous route, seed the parenchyma, and cause tissue destruction. Subsequently, some form mass lesions in a manner similar to neoplastic growths. The commonality in pathogenesis and pathology between infective agents and neoplastic cells underlies the similarities in their presentations. Although neoplasms are the common considerations in the presence of enhancing lesions with perilesional edema and mass effect on neuroimaging, nonneoplastic conditions-in particular, infectious lesions--can have similar imaging characteristics. The widening spectrum of opportunistic and newly recognized pathogens has added to the difficulties. Biopsy diagnosis is mandatory for neoplasms, both for confirmation of diagnosis as well as grading, but most infectious lesions are managed conservatively if the diagnosis is established by noninvasive means. This review discusses some of the common infectious lesions that mimic CNS neoplasms, with emphasis on pyogenic, tuberculous, and fungal lesions as well as parasitic and viral infections that present as intracranial space-occupying lesions. The data of infective lesions that mimicked intracranial neoplasms, from our institute, over the last 5 years, are also presented. Awareness of the pathogenetic basis of tissue injury and host response, resulting in the spectrum of clinical and imaging patterns as well as a high index of clinical suspicion, are essential for accurate diagnosis, to ensure appropriate management.

• Histological and immunohistochemical characterization of AT/RT: A report of 15 cases from India.

  Authors: Ishani Mohapatra, Vani Santosh, Yasha T Chickabasaviah, Anita Mahadevan, Ashwani Tandon, Amrita Ghosh, Balasubramaniam Chidambaram, Somanna Sampath, Indira Devi Bhagavatula, Bangalore Ashwathnarayana Chandramouli, Shastry V R Kolluri, Susarla Krishna Shankar

  Neuropathology : official journal of the Japanese Society of Neuropathology. 11/2009;

  Atypical teratoid rhabdoid tumor (AT/RT) is a highly malignant embryonal CNS tumor, generally unresponsive to any form of therapy, uniformly fatal within 1 year. We report 15 cases of AT/RT diagnosedAtypical teratoid rhabdoid tumor (AT/RT) is a highly malignant embryonal CNS tumor, generally unresponsive to any form of therapy, uniformly fatal within 1 year. We report 15 cases of AT/RT diagnosed at our center over a period of 5 years (2003-08). Tumors were located in different sites of the neuraxis, posterior fossa being the most common (n = 10) followed by cerebral lobes (n = 3). There was one each at the supra sellar and cervical spinal regions, respectively. Radiologically most of the tumors were heterodense and enhancing heterogeneously. The tumors exhibited diverse histological profile that included rhabdoid and PNET areas in all cases, mesenchymal and epithelial areas in 73.3% and 53.3% cases, respectively. Necrosis was evident in all cases and one showed calcification. Tumor cells displayed a polyphenotypic immunoprofile. All cases were consistently positive for vimentin and epithelial membrane antigen and were negative for desmin. Variable positivity was seen for other markers. The number of cases positive for these were: CK (53%), SMA (60%), synaptophysin (66%), NFP (33.3%) and GFAP (85%). CK staining was prominent in epithelial areas, while PNET cells labeled prominently with synaptophysin. There was lack of INI1 expression in all cases. Follow-up was available in 46.6% of cases which revealed a uniform poor prognosis.

• Clinicopathological study of tuberculous brain abscess.

  Authors: Shrijeet Chakraborti, Anita Mahadevan, Aparna Govindan, S Nagarathna, Vani Santosh, T C Yasha, B Indira Devi, B A Chandramouli, Jerry M E Kovoor, A Chandramuki, S K Shankar

  Pathology, research and practice. 08/2009;

  Central nervous system tuberculosis is still one of the leading causes of morbidity in the developing world, and tuberculous abscess is one of its uncommon manifesting forms. It closely mimics aCentral nervous system tuberculosis is still one of the leading causes of morbidity in the developing world, and tuberculous abscess is one of its uncommon manifesting forms. It closely mimics a pyogenic abscess clinically, radiologically, and histologically. An accurate diagnosis is imperative due to therapeutic implications. In this study, 21 cases of tuberculous abscesses encountered over a period of 13 years (1995-2007) were reviewed to study the clinical, radiological, and histopathological spectrum of the disease. The presence of palisading epithelioid cells and sheets of foamy histiocytes, enclosing a neutrophillic exudate rich in fibrin with nuclear debris, were clues as to suspicion of a tuberculous abscess. The demonstration of acid fast bacilli in the wall of the abscess or necrotic contents by microscopy or culture is essential to confirm the diagnosis of tuberculous abscess. A high index of clinical suspicion is necessary particularly in countries endemic for tuberculosis to ensure an accurate diagnosis and application of an appropriate therapy.

• Fabry's disease: An ultrastructural study of nerve biopsy.

  Authors: N Gayathri, T C Yasha, Makarand Kanjalkar, Santosh Agarwal, B K Chandrashekar Sagar, Vani Santosh, S K Shankar

  Annals of Indian Academy of Neurology. 07/2008; 11(3):182-4.

  Fabry's disease, an X linked recessive disorder caused by the deficiency of alpha-galactosidase A (alpha-gal A), leads to progressive accumulation of glycosphingolipids. We report this rare diseaseFabry's disease, an X linked recessive disorder caused by the deficiency of alpha-galactosidase A (alpha-gal A), leads to progressive accumulation of glycosphingolipids. We report this rare disease in a 19-year-old boy who presented with angiokeratomas, paresthesia and corneal opacities, and nerve biopsy revealed by electron microscopy lamellated inclusions in the smooth muscle, perineurial and endothelial cells characteristic of Fabry's disease.

• Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis.

  Authors: Sreekanth P Reddy, Ramona Britto, Katyayni Vinnakota, Hebbar Aparna, Hari Kishore Sreepathi, Balaram Thota, Arpana Kumari, B M Shilpa, M Vrinda, Srikantha Umesh [......] Ashwani Tandon, Paritosh Pandey, Sridevi Hegde, A S Hegde, Anandh Balasubramaniam, B A Chandramouli, Vani Santosh, Paturu Kondaiah, Kumaravel Somasundaram, M R Satyanarayana Rao

  Clinical cancer research : an official journal of the American Association for Cancer Research. 06/2008; 14(10):2978-87.

  PURPOSE: Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis,PURPOSE: Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. EXPERIMENTAL DESIGN: We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade II--diffuse astrocytoma, grade III--anaplastic astrocytoma, and grade IV--glioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). RESULTS: We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage-inducible alpha (GADD45alpha) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45alpha and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45alpha conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival. CONCLUSIONS: Our study reveals that GADD45alpha and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45alpha overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM patients.

• PBEF1/NAmPRTase/Visfatin: a potential malignant astrocytoma/glioblastoma serum marker with prognostic value.

  Authors: P Sreekanth Reddy, Srikantha Umesh, Balaram Thota, Ashwani Tandon, Paritosh Pandey, A S Hegde, Anandh Balasubramaniam, B A Chandramouli, Vani Santosh, M R S Rao, Paturu Kondaiah, Kumaravel Somasundaram

  Cancer biology & therapy. 06/2008; 7(5):663-8.

  Malignant astrocytomas comprise anaplastic astrocytoma (AA; grade III) and Glioblastoma (GBM; grade IV). GBM is the most malignant with a median survival of 10-12 months in patients. Using cDNAMalignant astrocytomas comprise anaplastic astrocytoma (AA; grade III) and Glioblastoma (GBM; grade IV). GBM is the most malignant with a median survival of 10-12 months in patients. Using cDNA microarray based expression profiling of different grades of astrocytomas, we identified several fold increased levels of PBEF1 transcripts in GBM samples. Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes Nicotinamide phosphoribosyltransferase (NAmPRTase), which catalyses the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. Further validation using real time RT-qPCR on an independent set of tumor samples (n=91) and normal brain samples (n=9), GBM specific higher expression of PBEF1 was confirmed. Immunohistochemical staining for PBEF1 on a subset of the above samples largely reinforced our finding. We carried out ELISA analysis on serum samples of astrocytoma patients to determine whether this protein levels would correlate with the presence of tumor and tumor grade. PBEF1 serum levels were substantially elevated in many of the AA and GBM patients. Statistical analysis of these data indicates that in patients with astrocytoma, serum PBEF1 levels correlate with tumor grade and is highest in GBM. Immunohistochemical analysis of an independent set of 51 retrospective GBM cases with known survival data revealed that PBEF1 expression in the tumor tissue along with its co-expression with p53 was associated with poor survival. Thus, we have identified PBEF1 as a potential malignant astrocytoma serum marker and prognostic indicator among GBMs.