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自发性犬脑胶质瘤:组织微阵列免疫表型分析显示 EGFR、PDGFRalpha 和 IGFBP2 的过表达。

Spontaneous canine gliomas: overexpression of EGFR, PDGFRalpha and IGFBP2 demonstrated by tissue microarray immunophenotyping.

机构信息

Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.

出版信息

J Neurooncol. 2010 May;98(1):49-55. doi: 10.1007/s11060-009-0072-5. Epub 2009 Dec 5.

DOI:10.1007/s11060-009-0072-5
PMID:19967449
Abstract

Fifty-seven spontaneous canine gliomas were histologically classified and graded using the latest World Health Organization (WHO 2007) criteria for classification of human gliomas. A total of 19 canine astrocytomas were classified as follows: grade IV (GBM) n = 7; grade III n = 5; and grade II, n = 7. Thirty-eight oligodendrogliomas were classified as either grade III (anaplastic) n = 35 or low grade II n = 3. Tissue microarray (TMA) immunohistochemistry was used to evaluate tumor expression of EGFR, PDGFRa and IGFBP2, three key molecules of known pathophysiological importance in human gliomas. Findings were correlated with tumor classification and grade. Increased EGFR expression was demonstrated in 57% of GBMs, 40% of grade III and 28% of grade II astrocytomas. EGFR expression occurred in only 3% of grade III oligodendrogliomas. Increased expression of PDGFRalpha was demonstrated in 43% of GBMs, 20% of grade III, and 14% of grade II astrocytomas. In the oligodendroglioma series, 94% of grade III tumors overexpressed PDGFRalpha. IGFBP2 expression was detected in 71, 60 and 28% of GBMs, grade III and grade II astrocytomas respectively. IGFBP2 expression occurred in 48% of anaplastic and in 33% of low grade oligodendrogliomas. Expression of EGFR, PDGFRalpha or IGFBP2 was not detected in normal canine CNS control TMA cores. The incidence of overexpression of EGFR, PDGFRalpha and IGFBP2 in these canine gliomas closely parallels that in human tumors of similar type and grade. These findings support a role for the spontaneous canine glioma model in directed pathway-targeting therapeutic studies.

摘要

57 例自发性犬脑胶质瘤采用最新的世界卫生组织(WHO 2007)人类胶质瘤分类标准进行了组织学分类和分级。共 19 例犬星形细胞瘤分类如下:IV 级(GBM)n = 7;III 级 n = 5;和 II 级,n = 7。38 例少突胶质细胞瘤分为 III 级(间变性)n = 35 或低级别 II 级 n = 3。组织微阵列(TMA)免疫组织化学用于评估肿瘤中 EGFR、PDGFRa 和 IGFBP2 的表达,这三个分子在人类胶质瘤中具有已知的病理生理重要性。结果与肿瘤分类和分级相关。在 57%的 GBM、40%的 III 级和 28%的 II 级星形细胞瘤中显示 EGFR 表达增加。在 3%的 III 级少突胶质细胞瘤中发现 EGFR 表达增加。在 43%的 GBM、20%的 III 级和 14%的 II 级星形细胞瘤中显示 PDGFRalpha 表达增加。在少突胶质细胞瘤系列中,94%的 III 级肿瘤过度表达 PDGFRalpha。IGFBP2 在 71%、60%和 28%的 GBM、III 级和 II 级星形细胞瘤中被检测到。IGFBP2 在 48%的间变性和 33%的低级别少突胶质细胞瘤中表达。在正常犬中枢神经系统对照 TMA 核心中未检测到 EGFR、PDGFRalpha 或 IGFBP2 的表达。这些犬脑胶质瘤中 EGFR、PDGFRalpha 和 IGFBP2 的过度表达发生率与类似类型和分级的人类肿瘤非常相似。这些发现支持自发性犬脑胶质瘤模型在定向途径靶向治疗研究中的作用。

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