Activation of the PI3K/Akt/mTOR pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder.
|核心内容：
目的：磷脂酰肌醇3-激酶(PI3K)/Akt/哺乳动物雷帕霉素靶点(MTOR)通路异常参与尿路上皮癌的发生发展。 然而，它的临床相关性还没有在人体样本中得到实质性的验证。 这项研究的目的是利用组织微阵列技术评估该通路在大量膀胱癌队列中的表达。 方法与结果：对887例鼻咽癌进行了磷酸酶和紧张素同源物(PTEN)、磷酸化Akt、mTOR、S6和4E-BP1的免疫组织化学染色，并与临床病理特征进行了比较。 P-S6和p-Akt的高表达与高级别和晚期肿瘤显著相关，而PTEN和p-4E-BP1的缺失在高级别和高分期肿瘤中更常见 。
P-Akt和p-S6的高表达预测了经尿道电切治疗的非肌肉浸润性癌症的进展和肿瘤特异性死亡率，p-Akt是多因素分析中的一个独立因素。 P-mTOR和p-Akt的高表达与肌肉浸润性癌较高的肿瘤特异性死亡率相关，p-mTOR是一个独立的预后因素。 结论：我们已经证实了PI3K/Akt/mTOR改变对膀胱肿瘤生物学行为的影响。 正确的免疫组化检测PI3K/Akt/mTOR通路可以提供有用的预后信息，这一发现可能为膀胱癌的治疗提供新的治疗途径。
AIMS:Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway dysregulation has been implicated in the development of urothelial carcinoma. However, its clinical relevance has not been substantially validated in human samples. The aim of this study was to assess the expression of the pathway in a large cohort of bladder cancers using the tissue microarray technique. METHODS AND RESULTS:Immunohistochemical stains for phosphatase and tensin homologue (PTEN), phosphorylated Akt, mTOR, S6 and 4E-BP1 were performed for 887 cases, and the results were correlated with clinicopathological characteristics. The high expression of p-S6 and p-Akt corresponded significantly with high-grade and advanced-stage, while losses of PTEN and p-4E-BP1 were observed more often in high-grade and high-stage tumours. High expression of p-Akt and p-S6 predicted progression and cancer-specific mortality for non-muscle-invasive cancers treated by transurethral resection, and p-Akt was an independent factor in multivariate analysis. High expression of p-mTOR and p-Akt correlated with higher cumulative incidence of cancer-specific mortality for muscle-invasive cancer, and p-mTOR was an independent prognostic factor. CONCLUSIONS:We have demonstrated the impact of PI3K/Akt/mTOR alteration on the biological behaviour of bladder tumours. Proper immunohistochemical examination of the PI3K/Akt/mTOR pathway can provide useful prognostic information, and the findings may represent an additional therapeutic avenue in the treatment of bladder cancers.
参考文献：https:///10.1111/j.1365-2559.2011.03856.x
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