Automated quantitative analysis of activator protein-2α subcellular expression in melanoma tissue microarrays correlates with survival prediction
Automated quantitative analysis of activator protein-2α subcellular expression in melanoma tissue microarrays correlates with survival prediction
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DOI：
10.1158/0008-5472.can-05-2300
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发表时间：
2005-12-01
期刊：
影响因子：
11.2
通讯作者：
Bar-Eli, M
中科院分区：
文献类型：
--
作者：
Berger, AJ;Davis, DW;Bar-Eli, M
激活蛋白-2 α（AP-2）转录因子在调节参与人黑色素瘤的肿瘤生长和转移的基因表达中起关键作用。我们试图评估AP-2表达的预后意义及其在痣向转移性黑色素瘤转变中的作用。分析了两个队列。一个是一个“进展”微阵列，包含来自医学博士的黑色素瘤标本。安德森癌症中心代表84例，另一个是耶鲁大学的回顾性队列，代表214例原发性黑色素瘤和293例转移瘤。采用两种定量系统[自动定量分析（AQUA）和激光扫描细胞仪（LSC）]分析总AP-2表达，结果显示与诊断组无关。MD的LSC分析。安德森癌症中心阵列显示，表达核AP-2的细胞数量在良性痣组中最高（11.85%），并且在黑色素瘤进展的各个阶段中显著降低，在转移组中为0.39%。LSC和AQUA均显示细胞核AP-2水平降低，细胞质AP-2水平升高，这与进展成正比。细胞核和细胞质表达水平均与预后无关。有趣的是，细胞质与细胞核AP-2的比值预测了整个人群和单独原发性肿瘤的结果，证明了该比值对变异进行标准化的能力。AP-2比值与Breslow深度等临床病理因素呈正相关（R = 0.334，P < 0.001）。我们发现AP-2在细胞质中的高水平表达与预后不良相关，而细胞核AP-2表达的缺失与黑色素瘤的恶性转化和进展相关。
The activator protein-2 alpha, (AP-2) transcription factor plays a key role in regulating expression of genes involved in tumor growth and metastasis of human melanoma. We sought to assess the prognostic significance of AP-2 expression and its role in the transition of nevi to metastatic melanoma. Two cohorts were analyzed. One was a "progression" microarray containing melanoma specimens from M.D. Anderson Cancer Center representing 84 cases and the other was a retrospective cohort from Yale University representing 214 primary melanomas and 293 metastases. Analysis of total AP-2 expression using two quantitative systems [automated quantitative analysis (AQUA) and laser scanning cytometry (LSC)] revealed no correlation with diagnosis group. LSC analysis of the M.D. Anderson Cancer Center array showed that the number of cells expressing nuclear AP-2 was highest in the benign nevi group (11.85%) and significantly decreased in each phase of melanoma progression to 0.39% in the metastatic group. Both LSC and AQUA showed decreased nuclear AP-2 levels and increased cytoplasmic AP-2 that is directly proportional to progression. Neither nuclear nor cytoplasmic expression levels correlated with outcome. Intriguingly, the ratio of cytoplasmic to nuclear AP-2 predicted outcome in the entire population and in the primary tumors alone, demonstrating the power of the ratio to normalize for variations. Furthermore, the AP-2 ratio directly correlated with other clinicopathologic factors, including Breslow depth (R = 0.334, P < 0.001). We show that a high level of AP-2 expression in the cytoplasm relative to the nucleus correlates with poor prognosis and the loss of nuclear AP-2 expression is associated with malignant transformation and progression of melanoma.