Puglisi F, Aprile G, Minisini A M, Barbone F, Cataldi P, Tell G, Kelley M R, Damante G, Beltrami C A, Di Loreto C
University of Udine, Italy.
Anticancer Res. 2001 Nov-Dec;21(6A):4041-9.
To evaluate the prognostic value of the DNA repair/redox-protein Ape1/ref-1 in a retrospective series of consecutive non-small cell lung carcinomas (NSCLC).
Sections from 91 radically resected NSCLC were analyzed for immunohistochemical expression of Ape1/ref-1. For each case 1,000 tumor cells were evaluated to detect nuclear and cytoplasmic reactivity scored as a percentage of positive cells. With respect to sub-cellular localization and percentage of immunoreactive cells, each tumor was classified as "cytoplasmic" or "non cytoplasmic". The survival rate according to Ape1/ref-1 sub-cellular localization was calculated.
The main pattern of Ape1/ref-1 expression was nuclear. No significant difference was observed in Ape1/ref-1 pattern according to histotype (squamous vs adenocarcinoma). Among adenocarcinomas, a cytoplasmic expression of Ape1/ref-1 was significantly associated with poor survival rate in univariate (p=0.01) and multivariate (p=0.07) analyses. In addition, a cytoplasmic expression of the DNA repair protein was also predictive of worse prognosis (log-rank test, p=0.02) in cases with lymph node involvement, regardless of histotype.
The results suggest a potential role of Ape1/ref-1 sub-cellular localization as a prognostic indicator in patients with NSCLC. In particular, cytoplasmic localization of the protein seems to confer a poor outcome in subgroups of patients with nodal involvement or adenocarcinoma histotype.
在一系列连续的非小细胞肺癌（NSCLC）回顾性研究中评估DNA修复/氧化还原蛋白Ape1/ref-1的预后价值。
对91例接受根治性切除的NSCLC切片进行Ape1/ref-1免疫组化表达分析。对每例病例评估1000个肿瘤细胞，以检测核和细胞质反应性，按阳性细胞百分比评分。根据亚细胞定位和免疫反应性细胞百分比，将每个肿瘤分类为“细胞质型”或“非细胞质型”。计算根据Ape1/ref-1亚细胞定位的生存率。
Ape1/ref-1表达的主要模式为细胞核型。根据组织学类型（鳞状细胞癌与腺癌），Ape1/ref-1模式未观察到显著差异。在腺癌中，Ape1/ref-1的细胞质表达在单因素分析（p=0.01）和多因素分析（p=0.07）中均与较差的生存率显著相关。此外，无论组织学类型如何，在有淋巴结受累的病例中，DNA修复蛋白的细胞质表达也预示着更差的预后（对数秩检验，p=0.02）。
结果表明Ape1/ref-1亚细胞定位在NSCLC患者中作为预后指标具有潜在作用。特别是，该蛋白的细胞质定位似乎在有淋巴结受累的患者亚组或腺癌组织学类型中预示着不良结局。
