Expression of hypoxia-related tissue factors in astrocytic gliomas. A multivariate survival study with emphasis upon carbonic anhydrase IX

Korkolopoulou, Penelope; Perdiki, Μarina; Thymara, Irene; Boviatsis, Efstathios; Agrogiannis, George; Kotsiakis, Xenophon; Angelidakis, Dimitrios; Rologis, Dimitrios; Diamantopoulou, Kalliopi; Thomas-Tsagli, Euphemia; Kaklamanis, Loukas; Gatter, Kevin C.; Patsouris, Efstratios

doi:10.1016/j.humpath.2006.07.020

Cited by 47 publications

(44 citation statements)

References 30 publications

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“…This result makes CA VII another CA isozyme with a significant correlation to the patient survival. Indeed, the previous studies have demonstrated that CA II, CA IX and CA XII all show similar trends as prognostic markers in diffuse astrocytomas [6,7,25,39]. The presence of several CA isozymes in astrocytomas may reflect the rapid turnover of acid metabolic products in highly malignant tumor tissues.…”

Section: Discussionmentioning

confidence: 90%

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Bootorabi¹,

Haapasalo²,

Smith³

et al. 2011

Health

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Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII expression in a cohort of human diffuse astrocytomas, mixed oligoastrocytomas and oligodendrogliomas. CA VII immunostaining was correlated to clinicopathologic findings, survival data, and expression of other molecular factors, including Ki-67, p53 protein and epidermal growth factor receptor. CA VII-positive staining was observed in 94% of astrocytomas and 85% of oligodendrogliomas. In the tumor specimens, strong positive areas were often located in close proximity to necrosis. The CA VII immunoreactivity showed positive correlation with tumor malignancy grades of astrocytomas (p = 0.02, chi-square test). In all tumor categories, CA VII-positive staining was often seen in the endothelial cells of neovessels in addition to the tumor cells. CA VII intensity showed no significant association with p53 nor did it correlate with the amplification of epidermal growth factor receptor (analyzed only in astrocytomas) or cell proliferation. Our present results show that CA VII may act as a useful biomarker in histopathologic diagnostics of gliomas. The high expression of CA VII in the tumor cells and endothelium suggests important roles for the enzyme in tumor metabolism. The results also led us to conclude that CA VII might serve as a marker of poor prognosis in diffuse astrocytomas.

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Section: Discussionmentioning

confidence: 90%

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Bootorabi¹,

Haapasalo²,

Smith³

et al. 2011

Health

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“…Also, VEGF and microvascular characteristics were not included in survival analysis because their prognostic significance has been the subject of previous investigations (17,18). Statistical calculations were performed using the Statistical package STATA 9.0 for Windows.…”

Section: Discussionmentioning

confidence: 99%

Expression of Interleukin-8 Receptor CXCR2 and Suppressor of Cytokine Signaling-3 in Astrocytic Tumors

Korkolopoulou

Levidou

El-Habr

et al. 2012

Mol Med

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The aim was to expand recently published information regarding the significance of the interleukin (IL)-8/p-STAT-3 (signal transducer and activator of transcription) pathway in astrocytomas, focusing on the IL-8 receptor, chemokine (C-X-C motif) receptor 2 (CXCR2), and the STAT-3 inhibitor SOCS-3 (suppressors of cytokine signaling). A total of 91 paraffin-embedded human astrocytoma tissues (grades II-IV) were investigated for the association of SOCS-3 and CXCR2 expression with clinicopathologic and morphometric microvascular characteristics, vascular endothelial growth factor (VEGF), IL-8 and p-STAT-3 expression and patient survival. Peripheral IL-8 secretion levels were assessed by enzyme-linked immunosorbent spot (ELISPOT). SOCS-3, p-STAT-3 and CXCR2 protein levels were also quantified by Western immunoblotting in six cases, and the protein levels of SOCS-3 and CXCR2 were correlated with the immunohistochemical expression of the respective proteins. All CXCR2-positive cases by Western immunoblotting displayed increased peripheral IL-8 secretion levels. Treatment of primary glioblastoma cell cultures with exogenous IL-8 enhanced proliferation, and this effect was inhibited by treatment with a neutralizing anti-CXCR2 antibody. SOCS-3 and CXCR2 were expressed by neoplastic astrocytes in 92.4% and 48.78% of cases, respectively, with their levels increasing with histological grade and extent of necrosis. VEGF expression and microvessel density, CXCR2 and IL-8 levels were interrelated. SOCS-3 and p-STAT-3 were coexpressed in 85.7% of cases, although they were not interrelated. In univariate survival analysis, increased SOCS-3 expression and the presence of CXCR2 adversely affected survival, whereas in multivariate analysis, only CXCR2 remained significant. The prognostic significance of CXCR2 was validated in an independent set of 63 patients. Our data implicate IL-8/CXCR2 signaling pathway in the progression and regulation of angiogenesis in astrocytomas and provide a rationale for CXCR2 therapeutic exploitation in these tumors.

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“…The same authors also showed that acidification of the tumour microenvironment is attributed to the accumulation not only of lactic acid, but also of CO 2 , suggesting a possible contribution of carbonic anhydrase 9 (CA9). CA9 is induced by hypoxia and its expression is correlated with malignancy in gliomas [92][93][94][95]. There is evidence that CA9 is involved in the regulation of both extracellular and intracellular pH [96,97] suggesting that CA9 activity is needed for the survival of hypoxic cells and that its inhibition may represent a promising therapeutic approach.…”

Section: Hif-1 Regulated Metabolismmentioning

confidence: 99%

Hypoxia Helps Glioma to Fight Therapy

Amberger-Murphy

2009

CCDT

101

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Abstract:Despite major improvements in the surgical management the prognosis for patients bearing malignant gliomas is still dismal. Malignant gliomas are notoriously resistant to treatment and the survival time of patients is between 3-8 years for low-grade and anaplastic gliomas and 6 -12 month for glioblastoma. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumour vasculature leading to insufficient blood supply, hypoxic areas and ultimately to the formation of necrosis, a characteristic of glioblastoma. Hypoxic/necrotic tumours are more resistant to chemotherapy and radiation. Hypoxia induces either directly or indirectly (through the activation of transcription factors) changes in the biology of a tumour and its microenvironment leading to increased aggressiveness and tumour resistance to chemotherapy and radiation. This review is focused on hypoxia-induced molecular changes affecting glioma biology and therapy.3

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Expression of hypoxia-related tissue factors in astrocytic gliomas. A multivariate survival study with emphasis upon carbonic anhydrase IX

Cited by 47 publications

References 30 publications

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Expression of Interleukin-8 Receptor CXCR2 and Suppressor of Cytokine Signaling-3 in Astrocytic Tumors

Hypoxia Helps Glioma to Fight Therapy

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