Downregulation of transcription factor AP-2 predicts poor survival in stage I cutaneous malignant melanoma
Downregulation of transcription factor AP-2 predicts poor survival in stage I cutaneous malignant melanoma
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DOI：
10.1200/jco.1998.16.11.3584
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发表时间：
1998-11-01
影响因子：
45.3
通讯作者：
Kosma, VM
中科院分区：
文献类型：
--
作者：
Karjalainen, JM;Kellokoski, JK;Kosma, VM
目的：转录因子激活蛋白（AP）-2，一个52 kd的DNA结合蛋白，被认为是通过激活p21抑制肿瘤生长。为了验证这一假设，我们分析了AP-2和p21蛋白表达在I期皮肤恶性黑色素瘤，以澄清其意义方面的肿瘤进展和survival.Patients和方法：一个连续系列的369临床I期皮肤恶性黑色素瘤患者进行了研究，采用免疫组化。检测到的表达水平彼此相关，与临床病理数据，并与黑色素瘤生存。AP-2表达缺失与p21低表达显著相关（P = 0.007），肿瘤厚度高（P = 0.001）、高Clark水平（P = 0.046）、高肿瘤淋巴结转移（TNM）类别（P = 0.006）、复发疾病（P = 0.001）和男性（P = 0.03）。肿瘤厚度、Clark's分期、TNM分期、出血量、AP-2指数、性别依次为恶性黑色素瘤无复发生存期（RFS）和总生存期（OS）的重要预测因素。在考克斯的多变量分析中，高肿瘤厚度（P = 0.0001）、低AP-2指数（P = 0.0153）和出血（P = 0.0143）预测RFS较差。高肿瘤厚度（P =.0008）和出血（P =.0092）预测OS较差。结论：AP-2表达缺失可能与皮肤恶性黑色素瘤的恶性转化和肿瘤进展有关。AP-2的这种肿瘤抑制作用可能通过p21调节介导。此外，AP-2表达降低与I期皮肤恶性黑色素瘤后续转移行为风险升高独立相关。(C)1998年，美国临床肿瘤学会。
Purpose: The transcription factor, activator protein (AP)-2, a 52-kd DNA-binding protein, is suggested to inhibit tumor growth through the activation of p21. To test this hypothesis, we analyzed AP-2 and p21 protein expressions in stage I cutaneous malignant melanomas to clarify their significance with regard to tumor progression and survival.Patients and Methods: A consecutive series of 369 clinical stage I cutaneous malignant melanoma patients were investigated using immunohistochemistry. The detected expression levels were correlated with each other, with clinicopathologic data, and with melanoma survival.Results: The loss of AP-2 expression was significantly associated with low p21 expression (P = .007), high tumor thickness (P = .001), high Clark's level (P = .046), high tumor-node-metastasis (TNM) category (P = .006), recurrent disease (P = .001), and male sex (P = .03). Tumor thickness, Clark's level, TNM category, bleeding, AP-2 index, and sex were all important predic tors of both recurrence-free survival (RFS) and overall survival (OS) of melanoma in this order. In Cox's multivariate analysis, high tumor thickness (P = .0001), low AP-2 index (P = .0153), and bleeding (P = .0143) predicted poor RFS. Poor OS was predicted by high tumor thickness (P = .0008) and bleeding (P = .0092).Conclusion: The loss of AP-2 expression seems to be associated with malignant transformation and tumor progression in cutaneous malignant melanoma. This tumor-suppressive action of AP-2 may be mediated through p21 regulation. Furthermore, decreased AP-2 expression is independently associated with elevated risk of subsequent metastatic behavior of stage I cutaneous malignant melanoma. (C) 1998 by American Society of Clinical Oncology.