Horiguchi Akio, Oya Mototsugu, Uchida Atsushi, Marumo Ken, Murai Masaru
Department of Clinical Research and Urology, National Saitama Hospital, Saitama, Japan.
J Urol. 2003 Feb;169(2):710-3. doi: 10.1097/01.ju.0000038952.59355.b2.
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.
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.
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.
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.
Akt与多种人类恶性肿瘤的发病机制及进展相关，因为Akt调节许多参与控制生存与凋亡平衡的关键效应分子。在各种类型的恶性肿瘤中均已证实Akt激活水平升高。在本研究中，我们评估了肾细胞癌中Akt的激活情况，并研究了其与病理特征及临床结局的关系。
使用仅识别活化Akt的抗磷酸化特异性Akt抗体，通过免疫组织化学对48例肾细胞癌患者的Akt激活情况进行评估。高免疫染色肿瘤定义为与相邻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当或降低的肿瘤。分析Akt激活状态与临床病理特征的关系。
在48例接受检查的患者中，与相邻非肿瘤性肾组织相比，18例（37.5%）表现出高抗磷酸化特异性Akt免疫染色，而30例（62.5%）表现出低免疫染色。免疫染色升高与肿瘤分级（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，在单因素分析中，高抗磷酸化特异性Akt免疫染色与较差的癌症特异性生存率显著相关（p = 0.叭09），但在多因素分析中则不然。
Akt激活水平升高可能是一个常见现象，尤其是在高级别肿瘤和转移性疾病中。它可能在肾细胞癌的发病机制及进展中起重要作用。
