Lkhagvadorj Sayamaa, Oh Sung Soo, Lee Mi-Ra, Jung Jae Hung, Chung Hyun Chul, Cha Seung-Kuy, Eom Minseob
Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea.
Department of Occupational & Environmental Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
Yonsei Med J. 2014 Jul;55(4):861-70. doi: 10.3349/ymj.2014.55.4.861.
Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers including renal cell carcinoma (RCC) with poor prognosis. Insulin receptor (IR) shares downstream effectors with IGF-1R; however, the expression and function of IR in the tumorigenesis of renal cancer remains elusive. Therefore, we examined the expression of IR and its prognostic significance in clear cell RCC (CCRCC).
Immunohistochemical staining for IR was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Eight of these cases were utilized for western blot analysis. The results were compared with various clinico-pathologic parameters of CCRCC and patient survival.
IR was expressed in the nuclei of CCRCC tumor cells in 109 cases (87.9%). Higher IR expression was significantly correlated with the presence of cystic change, lower Fuhrman nuclear grade, lower pathologic T stage, and lower TNM stage, although it wasn't significantly related to diabetes status and patient survival. Western blot analyses supported the results of the immunohistochemistry studies.
IR expression in CCRCC may be associated with favorable prognostic factors.
胰岛素和胰岛素样生长因子(IGF)-1信号传导都是能量代谢、细胞生长、增殖和存活的关键调节因子。IGF-1受体(IGF-1R)在包括肾细胞癌(RCC)在内的大多数人类癌症类型中过度表达,预后较差。胰岛素受体(IR)与IGF-1R共享下游效应器;然而,IR在肾癌发生中的表达和功能仍不清楚。因此,我们研究了IR在透明细胞肾细胞癌(CCRCC)中的表达及其预后意义。
对126例福尔马林固定石蜡包埋的CCRCC组织样本进行IR免疫组织化学染色。其中8例用于蛋白质印迹分析。将结果与CCRCC的各种临床病理参数和患者生存率进行比较。
109例(87.9%)CCRCC肿瘤细胞核中表达IR。较高的IR表达与囊性变的存在、较低的Fuhrman核分级、较低的病理T分期和较低的TNM分期显著相关,尽管它与糖尿病状态和患者生存率无显著相关性。蛋白质印迹分析支持免疫组织化学研究结果。
CCRCC中IR的表达可能与良好的预后因素相关。