Prognostic significance of activated Akt expression in melanoma: A clinicopathologic study of 292 cases
Prognostic significance of activated Akt expression in melanoma: A clinicopathologic study of 292 cases
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DOI：
10.1200/jco.2005.07.168
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发表时间：
2005-03-01
影响因子：
45.3
通讯作者：
Li, G
中科院分区：
文献类型：
--
作者：
Dai, DL;Martinka, M;Li, G
PurposeAkt 是一种丝氨酸/苏氨酸激酶，可刺激细胞周期进程、细胞增殖和抑制细胞凋亡。为了探讨Akt在黑色素瘤发病机制中的作用，我们检测了不同阶段黑色素细胞病变中磷酸Akt（p-Akt，Ser-473）的表达，并分析了p-Akt表达水平与临床病理因素和患者生存之间的相关性。患者和方法我们评估了12例正常痣、58例异常增生痣、 使用组织微阵列和免疫组织化学方法对 170 例原发性黑色素瘤和 52 例黑色素瘤转移瘤进行研究。结果在正常痣、发育不良痣、原发性黑色素瘤和黑色素瘤转移灶的活检组织中，分别观察到强 p-Akt 表达的比例为 17%、43%、49% 和 77%。在正常痣和原发性黑色素瘤之间（P < .05）以及原发性黑色素瘤和黑色素瘤转移之间（P < .001）观察到 p-Akt 染色模式的显着差异。此外，我们的 Kaplan-Meier 生存曲线显示，p-Akt 的强表达与原发性黑色素瘤患者的总体和疾病特异性 5 年生存率呈负相关（两者 P < .05）。引人注目的是，我们的多变量 Cox 回归分析显示，p-Akt 是低风险黑色素瘤（厚度小于或等于 1.5 mm；相对风险，6.44，95% CI，1.28 至 32.55；P = .018）的独立预后因素。结论 p-Akt 的表达随着黑色素瘤的侵袭和进展而显着增加，与患者生存呈负相关。此外，p-Akt 可作为独立的预后标志物，有助于识别死亡风险较高的低风险黑色素瘤患者。
PurposeAkt is a serine/threonine kinase that leads to stimulation of cell cycle progression, cell proliferation, and inhibition of apoptosis. To investigate the role of Akt in melanoma pathogenesis, we examined the expression of phospho-Akt (p-Akt, Ser-473) in melanocytic lesions at different stages and analyzed the correlations between the p-Akt expression level and clinicopathologic factors and patient survival.Patients and MethodsWe evaluated the p-Akt expression in 12 cases of normal nevi, 58 cases of dysplastic nevi, 170 cases of primary melanomas, and 52 cases of melanoma metastases using tissue microarray and immunohistochemistry.ResultsStrong p-Akt expression was observed in 17%, 43%, 49%, and 77% of the biopsies in normal nevi, dysplastic nevi, primary melanoma, and melanoma metastases, respectively. Significant differences for p-Akt staining pattern were observed between normal nevi and primary melanomas (P < .05), and between primary melanomas and melanoma metastases (P < .001). Furthermore, our Kaplan-Meier survival curves showed that strong p-Akt expression is inversely correlated with both overall and disease-specific 5-year survival of patients with primary melanoma (P < .05 for both). Strikingly, our multivariate Cox regression analysis revealed that p-Akt is an independent prognostic factor in low-risk melanomas (thickness less than or equal to 1.5 mm; relative risk, 6.44, 95% CI, 1.28 to 32.55; P = .018).ConclusionThe expression of p-Akt increases dramatically with melanoma invasion and progression and is inversely correlated with patient survival. In addition, p-Akt may serve as an independent prognostic marker and help to identify those patients with low-risk melanomas who are at increased risk of death.