Murtas Daniela, Piras Franca, Minerba Luigi, Ugalde Jorge, Piga Michela, Maxia Cristina, Perra Maria Teresa, Sirigu Paola
Department of Cytomorphology, University of Cagliari, 09042 Monserrato (CA).
Oncol Lett. 2010 Jul;1(4):633-639. doi: 10.3892/ol_00000112. Epub 2010 Jul 1.
Nuclear factor (NF)- κB is one of the most important transcription factors that plays a crucial role in the regulation of a wide spectrum of genes involved in modulating the cell cycle, apoptosis, cell growth, angiogenesis, inflammation and the tissue invasiveness of highly malignant cells. NF-κB activity has been found to be constitutively elevated in a number of human tumors from either a haematological or solid origin, such as melanomas. In several studies, NF-κB activation was shown to be an adverse prognostic factor, and in melanoma it was proposed as an event that promotes tumor progression. This study aimed to evaluate whether NF-κB activation in tumor tissues, assessed by the expression of the NF-κB p65 subunit, has an effect on the survival of melanoma patients. The expression of NF-κB was immunohistochemically investigated, and the correlation with survival was analyzed. Furthermore, the immunostaining for p53 and survivin was evaluated, and the relationship of these apoptotic and anti-apoptotic factors with NF-κB expression was analyzed. Kaplan-Meier analysis showed that patients with low levels of NF-κB in the nuclei of tumor cells had a significantly longer survival compared to those with high levels. Multivariate analysis confirmed the predictive value of nuclear NF-κB, showing that its expression maintains significance after the model was adjusted using clinicopathological factors. The results demonstrate the correlation of NF-κB p65 nuclear staining with the disease-specific 5-year survival of melanoma patients and suggest that nuclear NF-κB p65 may be promising as an early independent prognostic factor in patients with primary cutaneous melanoma.
核因子(NF)-κB是最重要的转录因子之一,在调控参与调节细胞周期、细胞凋亡、细胞生长、血管生成、炎症以及高恶性细胞的组织侵袭性的广泛基因中发挥关键作用。已发现NF-κB活性在多种血液系统或实体来源的人类肿瘤(如黑色素瘤)中持续升高。在多项研究中,NF-κB激活被证明是一个不良预后因素,在黑色素瘤中它被认为是促进肿瘤进展的一个事件。本研究旨在评估通过NF-κB p65亚基表达评估的肿瘤组织中NF-κB激活是否对黑色素瘤患者的生存有影响。采用免疫组织化学方法研究NF-κB的表达,并分析其与生存的相关性。此外,评估p53和生存素的免疫染色,并分析这些凋亡和抗凋亡因子与NF-κB表达的关系。Kaplan-Meier分析表明,肿瘤细胞核中NF-κB水平低的患者与水平高的患者相比,生存期显著更长。多变量分析证实了核NF-κB的预测价值,表明在使用临床病理因素调整模型后其表达仍具有显著性。结果证明了NF-κB p65核染色与黑色素瘤患者疾病特异性5年生存率的相关性,并表明核NF-κB p65可能有望成为原发性皮肤黑色素瘤患者的早期独立预后因素。