Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma
Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma
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DOI：
10.1016/s0022-5347(05)63998-5
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发表时间：
2003-02-01
影响因子：
6.6
通讯作者：
Murai, M
中科院分区：
文献类型：
--
作者：
Horiguchi, A;Oya, M;Murai, M
目的：Akt参与多种人类恶性肿瘤的发病机制和进展，因为Akt调节参与控制存活和凋亡平衡的许多关键效应分子。Akt激活升高已在各种类型的恶性肿瘤中得到证实。在目前的研究中，我们评估Akt激活肾细胞癌，并探讨其与病理特征和临床outcome.Materials和方法：Akt激活进行了评价，免疫组化使用抗磷酸化特异性Akt抗体，它只识别激活Akt，在48例肾细胞癌。高免疫染色肿瘤定义为与邻近非肿瘤性肾组织相比染色强度增加的肿瘤，低免疫染色肿瘤定义为染色强度相等或降低的肿瘤。结果：48例肾肿瘤患者中，18例（37.5%）Akt阳性表达高于癌旁肾组织，30例（62.5%）Akt阳性表达低于癌旁肾组织。免疫染色水平升高与肿瘤分级（p = 0.0354）和转移性疾病（p = 0.0044）显著相关，而与肿瘤分期或组织学亚型无关。此外，高antiphospho-specific Akt免疫染色显着相关的单变量分析（p = 0.0109），但不多变量analysis.Conclusions：Akt激活升高可能是一个共同的发现，特别是在高级别肿瘤和转移性疾病的癌症特异性生存率差。它可能在肾细胞癌的发生和发展中起重要作用。
Purpose: Akt has been implicated in the pathogenesis and progression of numerous human malignant tumors because Akt regulates many key effector molecules involved in controlling the balance of survival and apoptosis. Elevated Akt activation has been demonstrated in various types of malignant tumors. In the current study we evaluated Akt activation in renal cell carcinoma and investigated its association with pathological features and clinical outcome.Materials and Methods: Akt activation was evaluated by immunohistochemistry using antiphospho-specific Akt antibody, which recognizes only activated Akt, in 48 patients with renal cell carcinoma. High immunostaining tumors were defined as tumors with increased staining intensity compared with adjacent nonneoplastic kidney tissue and low immunostaining tumors were defined as tumors with equivalent or decreased staining intensity. The association of Akt activation status with clinicopathological features was analyzed.Results: Of 48 patients examined 18 (37.5%) demonstrated high antiphospho-specific Akt immunostaining compared with adjacent nonneoplastic kidney tissue, while 30 (62.5% demonstrated low immunostaining. Elevated immunostaining was significantly associated with tumor grade (p = 0.0354) and metastatic disease (p = 0.0044), while it was not associated with tumor stage or histological subtype. In addition, high antiphospho-specific Akt immunostaining was significantly associated with a poor cancer specific survival rate on univariate analysis (p = 0.0109) but not on multivariate analysis.Conclusions: Elevated Akt activation could be a common finding, especially in high grade tumor and metastatic disease. It could have an important role in the pathogenesis and progression of renal cell carcinoma.