Laboratory of Oncology, IMBECU, National Research Council, Mendoza, Argentina.
Cell Stress Chaperones. 2012 Nov;17(6):779-90. doi: 10.1007/s12192-012-0350-6. Epub 2012 Jul 18.
In oligodendrogliomas, 1p loss of heterozygosity (LOH) is a predictor of good prognosis and treatment response. In contrast, in uveal melanomas, LOH of chromosome 3 has been linked to poor prognosis and downregulation of Hsp27. In the present study, we have analyzed the expression of heat-shock proteins (Hsps) to characterize subtypes of gliomas and their histopathologic features and to correlate with other molecular markers including LOH of 1p. Biopsies from patients with primary gliomas (n = 65) were analyzed by immunohistochemistry, chromogenic in situ hybridization and fluorescent in situ hybridization and methylation-specific PCR (MSP). Elevated Hsp27 and total Hsp70 expression levels were associated with high-grade astrocytomas (p = 0.0001 and p = 0.01, respectively). In grade III oligodendrogliomas, the Hsp27 levels were significantly higher (p = 0.03). Low O6-methylguanine-DNA methyltransferase (MGMT) expression was associated with grade II astrocytomas. Elevated β-catenin expression was associated with grade III/IV astrocytomas (p = 0.003); p53 (+) tumors were more frequently found in grade III/IV astrocytomas (p = 0,001). LOH on 1p was associated with oligodendroglial tumours. In addition, a higher Hsp27 expression correlated with LOH of 1p (p = 0.017); this was also tested in two glioma cell lines. MSP was successful in only six samples. No significant correlations were found for the other markers. In conclusion, in oligodendroglial tumors, Hsp27 appeared as a surrogate marker of LOH of 1p which could also help to predict the disease prognosis. In gliomas, p53, Hsp27, Hsp70, MGMT, and β-catenin correlated with histopathological characteristics, suggesting that these markers could predict the disease outcome and the response to treatments.
在少突胶质细胞瘤中,1p 杂合性缺失(LOH)是预后良好和治疗反应的预测因子。相比之下,在葡萄膜黑色素瘤中,3 号染色体的 LOH 与预后不良和 Hsp27 下调有关。在本研究中,我们分析了热休克蛋白(Hsps)的表达,以表征神经胶质瘤亚型及其组织病理学特征,并与其他分子标志物相关联,包括 1p 的 LOH。通过免疫组织化学、显色原位杂交和荧光原位杂交以及甲基化特异性 PCR(MSP)分析了原发性神经胶质瘤患者的活检标本(n=65)。Hsp27 和总 Hsp70 表达水平升高与高级别星形细胞瘤相关(p=0.0001 和 p=0.01)。在 3 级少突胶质细胞瘤中,Hsp27 水平显著升高(p=0.03)。低 O6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)表达与 2 级星形细胞瘤相关。β-连环蛋白表达升高与 3/4 级星形细胞瘤相关(p=0.003);p53(+)肿瘤在 3/4 级星形细胞瘤中更为常见(p=0.001)。1p 的 LOH 与少突胶质细胞瘤相关。此外,较高的 Hsp27 表达与 1p 的 LOH 相关(p=0.017);这也在两种神经胶质瘤细胞系中进行了测试。MSP 在仅 6 个样本中成功。其他标志物未发现显著相关性。总之,在少突胶质细胞瘤中,Hsp27 似乎是 1p LOH 的替代标志物,也有助于预测疾病预后。在神经胶质瘤中,p53、Hsp27、Hsp70、MGMT 和 β-连环蛋白与组织病理学特征相关,表明这些标志物可以预测疾病结局和治疗反应。