Cerebral cavernomas in adults and children express relaxin

OBJECTIVETo shed light on the role of relaxin in cerebral cavernous malformations (CCMs) in adults and children, the authors investigated endothelial cell (EC) expression of relaxin 1, 2, and 3; vascular endothelial growth factor receptor–1 and –2 (VEGFR-1 and -2); Ki-67; vascular geometry; and hemorrhage, as well as the clinical presentation of 32 patients with surgically resected lesions.METHODSParaffin-embedded sections of 32 CCMs and 5 normal nonvascular lesion control (NVLC) brain tissue samples were immunohistochemically stained with antibodies to relaxin 1, 2, and 3; angiogenesis growth factor receptors Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2); and proliferation marker Ki-67. For morphometric analysis, Elastica van Gieson stain was used, and for hemorrhage demonstration, Turnbull stain was used. Data from the pediatric and adult CCMs were compared with each other and with those obtained from the NVLCs. Statistical analyses were performed with Fisher’s exact test, the chi-square test, the phi correlation coefficient, and the Student t-test. A p value < 0.05 was considered significant.RESULTSPediatric and adult cavernoma vessels did not significantly differ in diameter. Hemorrhage was observed in CCMs but not in NVLC samples (p < 0.05). There was no difference in expression of Ki-67, VEGFR-1 and -2, and relaxin 1, 2, and 3 in the ECs of pediatric and adult CCMs. The ECs of CCMs were largely negative for relaxin 3 compared to NVLCs (p < 0.05), whereas CCMs, compared to control brain tissue samples, more frequently expressed Flt-1 and relaxin 2 (p < 0.05). Ki-67 was not expressed in the NVLCs, but the difference was not statistically significant. Relaxin 1 and 2 expression and increased expression of VEGFR-1 were associated with a supra- versus infratentorial location (p < 0.05).CONCLUSIONSRelaxin 1 and 2 and VEGFR-1 play a role in supratentorial cavernomas. Relaxin 3 may play a physiological role in normal brain vasculature. Relaxin 1 and 3 are also found in normal cerebral vasculature. Relaxin 1, 2, and 3 are associated with increased VEGFR-1 expression.

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Exploring the role of epidermal growth factor receptor variant III in meningeal tumors

PLoS ONE ◽

10.1371/journal.pone.0255133 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0255133

Author(s):

Rashmi Rana ◽

Vaishnavi Rathi ◽

Kirti Chauhan ◽

Kriti Jain ◽

Satnam Singh Chhabra ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Benign Tumors ◽

P Value ◽

Ki 67 ◽

Epidermal Growth ◽

Immunohistochemical Techniques

Meningioma is the second most common type of intracranial brain tumor. Immunohistochemical techniques have shown prodigious results in the role of epidermal growth factor receptor variant III (EGFR vIII) in glioma and other cancers. However, the role of EGFR vIII in meningioma is still in question. This study attempt the confer searches for the position attained by EGFR vIII in progression and expression of meningioma. Immunohistochemistry technique showed that EGFR vIII is highly expressed in benign tumors as compared to the atypical meningioma with a highly significant p-value (p<0.05). Further analysis by flow cytometry results supported these findings thus presented high intensity of EGFR vIII in low grades of meningioma. The study revealed that the significant Ki 67 values, to predictor marker for survival and prognosis of the patients. Higher expression of EGFR vIII in low grades meningiomas as compared to high-grade tumors indicate towards its oncogenic properties. To our knowledge, limited studies reported in literature expressing the EGFR vIII in meningioma tumors. Hence, Opinions regarding the role that EGFR vIII in tumorigenesis and tumor progression are clearly conflicting and, therefore, it is crucial not only to find out its mechanism of action, but also to definitely identify its role in meningioma.

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Recurrent Glioblastomas Exhibit Higher Expression of Biomarkers with Stem-like Properties

Journal of Neurosciences in Rural Practice ◽

10.4103/jnrp.jnrp_417_17 ◽

2018 ◽

Vol 09 (01) ◽

pp. 086-091 ◽

Cited By ~ 2

Author(s):

B. N. Nandeesh ◽

Sharmistha Naskar ◽

Arun H. Shashtri ◽

A. Arivazhagan ◽

Vani Santosh

Keyword(s):

Growth Factor ◽

Growth Factor Receptor ◽

Normal Brain ◽

Tissue Samples ◽

Primary Tumors ◽

P53 Expression ◽

Sox2 Expression ◽

Paired Samples ◽

Recurrent Tumors ◽

Igfbp 3

ABSTRACT Background: Despite advances in the treatment of glioblastoma (GBM), the prognosis of patients continues to remain dismal. This unfavorable prognosis is mainly attributed to the tumor's propensity for progression and recurrence, which in turn is due to the highly aggressive nature of the persisting GBM cells that actively egress from the main tumor mass into the surrounding normal brain tissue. Such a recurrent tumor described to have a more malignant potential is highly invasive and resistant to current therapies, probably due to increased stemness and preferential selection of therapy-resistant clones of tumor cells. However, there is a paucity of literature on the expression of biomarkers in the recurrent GBM tumors that could have a role in conferring this aggressiveness. Aim: To identify the differences in the expression pattern of selected biomarkers in paired tissue samples of GBM. Material and Methods: A retrospective study on 30 paired samples of GBM (newly diagnosed/primary and recurrent) archived in the Department of Neuropathology, NIMHANS (2006–2009), was carried out. After obtaining clinical and demographic details, tumors were characterized histomorphologically and immunohistochemically on formalin-fixed paraffin-embedded tissues with reference to expression of biomarkers such as p53, epidermal growth factor receptor (EGFR), insulin-like growth factor binding protein 3 (IGFBP-3), sex determining region Y-box 2 (SOX2), and topoisomerase 2 A (Top2A). The results were statistically analyzed. Results: It was observed that while p53 and IGFBP-3 expression remained unaltered in paired samples, a significant increase in the expression of EGFR (P < 0.01) was noted in the recurrent tumors. Among the other biomarkers, SOX2 expression was higher in the recurrent tumors when compared to the primary tumors (P < 0.01). Conversely, the expression of Top2A was reduced in recurrent tumors (P = 0.05). Mild elevation in the expression of IGFBP-3 was observed in recurrent tumors but was not statistically significant. Conclusion: A significant increase in the expression of SOX2 in recurrent tumors probably indicates the presence of undifferentiated cells with stem-like properties in these tumors. EGFR is known to mediate SOX2 expression thereby resulting in stemness of the glioma cancer cells, which could further explain its overexpression in recurrent GBMs. Furthermore, a decreased expression of TOP2A observed in the recurrent tumors could probably be due to reduction in chemosensitivity to temozolomide, which has been shown in earlier studies. We also noted that p53 expression remained unaltered in the recurrent tumors when compared to the primary, suggesting the absence of preferential clonal expansion of p53 mutant cells following exposure to radiochemotherapy. Our study reiterates the fact that GBM recurrences are associated with molecular alterations that probably contribute to radiochemoresistance, increased invasiveness, therapeutic efficacy, and stemness.

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Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival

Cancers ◽

10.3390/cancers12010231 ◽

2020 ◽

Vol 12 (1) ◽

pp. 231 ◽

Cited By ~ 2

Author(s):

María González-Tablas ◽

Daniel Arandia ◽

María Jara-Acevedo ◽

Álvaro Otero ◽

Ana-Luisa Vital ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Expression Profile ◽

Expression Profiles ◽

Growth Factor Receptor ◽

Gene Expression Profiles ◽

Normal Brain ◽

Prognostic Impact ◽

Tissue Samples ◽

Intragenic Deletions

Background: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. Methods: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. Results: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8–9 was found in only two tumors (2%). Conclusions: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.

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Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients

Medical Principles and Practice ◽

10.1159/000494496 ◽

2018 ◽

Vol 28 (1) ◽

pp. 56-62

Author(s):

Cahit Kural ◽

Arzu Kaya Kocdogan ◽

Gulcin Güler Şimşek ◽

Serpil Oğuztüzün ◽

Pınar Kaygın ◽

...

Keyword(s):

Cytochrome P450 ◽

Brain Tissue ◽

Pituitary Adenomas ◽

Normal Brain ◽

Cytochrome P450 Enzyme ◽

Intracranial Tumors ◽

Glutathione S Transferase ◽

Normal Brain Tissue ◽

Tissue Samples ◽

P450 Enzyme

Objective: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. Subjects and Methods: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016–2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. Results: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. Conclusion: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes.

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