Department of Cytomorphology, University of Cagliari, Italy Cittadella Universitaria, 09042 Monserrato (CA), Italy.
Oncol Rep. 2010 Feb;23(2):329-35.
8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the main mutagenic modifications induced in DNA by oxidative stress. Elevated levels of 8-OHdG have been regarded as an independent prognostic factor in different types of cancer. Various enzymes, such as human 8-oxoguanine DNA-glycosylase 1 (hOGG1) and glucose-6-phosphate dehydrogenase (G6PD), act as protection against oxidative stress. The low activity of such enzymes has been consistently associated with increased risk of progression in several tumor types. The aim of this study was to investigate whether 8-OHdG, hOGG1 and G6PD expression in tumor tissues might be a predictor of survival in melanoma patients. The expression of 8-OHdG, hOGG1 and G6PD was immunohistochemically investigated in primary cutaneous melanoma and the effect on survival was analyzed. Furthermore, the immunostaining for p53 and survivin was evaluated and the relationship among 8-OHdG, hOGG1, G6PD, p53 and survivin expression was analyzed. Kaplan-Meier analysis demonstrated that patients with low expression of nuclear 8-OHdG had significantly longer survival time compared with those with a high expression (P=0.032), whereas cancer-specific survival of patients was not associated with hOGG1 or G6PD expression. These results suggest an involvement of oxidative DNA damage in the process of melanoma pathogenesis and demonstrate that 8-OHdG expression in nuclei of tumor cells could be useful as an early independent prognostic marker in patients with primary cutaneous melanoma.
8-羟基-2'-脱氧鸟苷(8-OHdG)是氧化应激诱导 DNA 中主要的诱变修饰之一。在不同类型的癌症中,升高的 8-OHdG 水平被认为是一个独立的预后因素。多种酶,如人 8-氧鸟嘌呤 DNA-糖苷酶 1(hOGG1)和葡萄糖-6-磷酸脱氢酶(G6PD),作为对抗氧化应激的保护机制。这些酶的低活性与几种肿瘤类型的进展风险增加密切相关。本研究旨在探讨肿瘤组织中 8-OHdG、hOGG1 和 G6PD 的表达是否可以预测黑色素瘤患者的生存情况。本研究采用免疫组织化学方法检测原发性皮肤黑色素瘤中 8-OHdG、hOGG1 和 G6PD 的表达,并分析其对生存的影响。此外,还评估了 p53 和 survivin 的免疫染色,并分析了 8-OHdG、hOGG1、G6PD、p53 和 survivin 表达之间的关系。Kaplan-Meier 分析表明,细胞核中 8-OHdG 低表达的患者与高表达的患者相比,生存时间明显更长(P=0.032),而 hOGG1 或 G6PD 表达与癌症特异性生存无关。这些结果表明,氧化 DNA 损伤参与了黑色素瘤发病机制,并表明肿瘤细胞核中 8-OHdG 的表达可能作为原发性皮肤黑色素瘤患者早期独立的预后标志物。