Nordfors K, Haapasalo J, Helén P, Paetau A, Paljärvi L, Kalimo H, Kinnula V L, Soini Y, Haapasalo H
Department of Pathology, Center for Laboratory Medicine, Tampere University Hospital, P.O. Box 2000, 33521 Tampere, Finland.
Clin Neuropathol. 2007 Sep-Oct;26(5):210-8. doi: 10.5414/npp26210.
Peroxiredoxins are antioxidant enzymes (AOEs), which are redox-regulated thiol proteins with potential effects on the growth, invasion and drug resistance of neoplastic cells. In this study, their biology and clinical significance were examined in pilocytic astrocytomas (PAs).
The expression of peroxiredoxins (Prx I-VI) was investigated in 105 PAs by the means of immunohistochemistry and compared with the expression of selected other antioxidant enzymes, cell proliferation, angiogenesis, apoptosis, p53, histopathology and patient survival.
Peroxiredoxins were strongly expressed in general suggesting that oxidative damage and consequent defense takes place during the progression of pilocytic astrocytomas. In agreement with this hypothesis, several other AOEs correlated with the degenerative features and angiogenesis possibly associated with reactive oxygen species-derived cellular damage. Moreover, the expression of the AOEs was associated with each other indicating a concurrent activation of the enzymes. With the exception of manganese superoxide dismutase (MnSOD), a strong expression of AOEs was generally associated with higher cell proliferation. Prx VI seemed to have a positive association with a longer recurrence-free interval while other AOEs had no association with patient survival. Many AOEs, such as MnSOD, induce chemo- and radioresistance and are highly elevated in aggressive malignancies. PAs lack this confounding factor, and these tumors are treated only by surgery.
Taken together, the results of this study on pilocytic astrocytomas suggest that the levels of Prxs and other AOEs and their related thiol proteins are generally strongly expressed in these tumors. At least Prx VI can contribute to tumor behavior which can make it a potential prognostic factor.
过氧化物还原酶是抗氧化酶（AOEs），是氧化还原调节的硫醇蛋白，对肿瘤细胞的生长、侵袭和耐药性具有潜在影响。在本研究中，研究了它们在毛细胞型星形细胞瘤（PAs）中的生物学特性和临床意义。
采用免疫组织化学方法研究了105例PAs中过氧化物还原酶（Prx I-VI）的表达，并与其他选定的抗氧化酶的表达、细胞增殖、血管生成、凋亡、p53、组织病理学和患者生存率进行了比较。
过氧化物还原酶总体上呈强表达，提示在毛细胞型星形细胞瘤进展过程中发生了氧化损伤及相应的防御反应。与该假设一致，其他几种AOEs与可能与活性氧衍生的细胞损伤相关的退行性特征和血管生成相关。此外，AOEs的表达相互关联，表明这些酶同时被激活。除锰超氧化物歧化酶（MnSOD）外，AOEs的强表达通常与较高的细胞增殖相关。Prx VI似乎与较长的无复发生存期呈正相关，而其他AOEs与患者生存率无关。许多AOEs，如MnSOD，可诱导化学耐药性和放射耐药性，在侵袭性恶性肿瘤中高度升高。PAs缺乏这一混杂因素，这些肿瘤仅通过手术治疗。
综上所述，本研究对毛细胞型星形细胞瘤的结果表明，Prxs和其他AOEs及其相关硫醇蛋白的水平在这些肿瘤中总体上呈强表达。至少Prx VI可影响肿瘤行为，这使其成为一个潜在的预后因素。
