摘要
目的:探讨磷酸化蛋白激酶B(phospho-protein kinase B,p-PKB,又称p-AKT)(h r308)和p-AKT(Ser473)蛋白在胃肠间质瘤(gastrointestinal stromal tumor,GIST)中的表达及其临床意义,并评价其在预测GIST预后方面的作用。方法:收集102例手术完整切除的原发性GIST患者肿瘤组织标本,制备组织芯片,应用免疫组织化学法检测p-AKT(h r308)和p-AKT(Ser473)蛋白的表达水平,并将检测结果与患者的临床病理特征和无复发生存期进行统计分析。结果:GIST组织中p-AKT(h r308)和p-AKT(Ser473)蛋白的阳性表达率分别为54.9%和56.9%,均高于相应的瘤旁组织(P<0.05)。p-AKT(h r308)表达与GIST肿瘤大小、核分裂象计数、美国国立卫生研究所(National Institute of Health,NIH)危险分级和5年无复发生存率均有相关性(P<0.05),而p-AKT(Ser473)表达与GIST原发部位、肿瘤大小、核分裂象计数、肿瘤细胞密度、肿瘤性坏死、NIH风险分级和5年无复发生存率相关(P<0.05)。单因素及多因素生存分析显示,p-AKT(h r308)和p-AKT(Ser473)两者均阳性表达的患者,其5年无复发生存率低于二者均阴性表达的患者(P<0.05)。结论:完全活化的AKT蛋白表达可能与GIST的发生、发展以及不良预后有关。联合检测p-AKT(h r308)和p-AKT(Ser473)蛋白表达水平有助于预测GIST的预后。
Objective： To investigate the clinicopathological significance of the expressions of phospho-protein kinase B （p-AKT） （Thr308） and p-AKT （Ser473） proteins in gastrointestinal stromal tumor （GIST） tissues and their impact on prognosis. Methods： Tumor samples and clinicopathological data from 102 patients with primary GIST after R0 resection were obtained. Immunohistochemical （IHC） analysis was performed based on tissue microarray （TMA） to estimate the expression pattern of p-AKT （Thr308） and p-AKT （Ser473） in tumor cells. The relationships of these two p-AKT protein expressions with clinicopathological characteristics and relapse-free survival （RFS） were also analyzed. Results： The positive expression rates of p-AKT （Thr308） and p-AKT （Ser473） proteins in GIST tissues were 54.9% and 56.9%, respectively, which were both higher than those in the adjacent normal gastrointestinal stromal tissues （P 〈 0.05）. The expression pattern of p-AKT （Thr308） was associated with tumor size, mitotic index, National Institute of Health （NIH） risk classification and 5-year RFS （P 〈 0.05）, while p-AKT （Ser473） expression was associated with primary tumor site, tumor size, mitotic index, tumor cellularity, necrosis, NIH risk classification and 5-year RFS （P 〈 0.05）. Univariate and multivariate survival analyses demonstrated that the 5-year RFS rate in the GIST patients whose p-AKT （Thr308） and p-AKT （Ser473） were both positively expressed was lower than that in the GIST patients whose p-AKT （Thr308） and p-AKT （Ser473） were both negatively expressed （P 〈 0.05）. Conclusion： The expression of totally activated AKT proteins may be correlated with the occurrence, development and poor prognosis of GIST. The evaluation of co-expression pattern of p-AKT （Thr308） and p-AKT （Ser473） proteins may help predict the prognosis of GIST patients.
出处
《肿瘤》
CAS
CSCD
北大核心
2014年第6期541-546,共6页
Tumor
