腎癌の間質組織におけるFerの発現は癌進展に抑制的に働き予後予測に有用である ; Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a useful predictor of survival

Nagasaki University (長崎大学) ; 博士(医学) ; Fps/Fes related (Fer) is a non?receptor tyrosine kinase that is expressed in fibroblasts, immune cells and endothelial cells. Fer serves an important pathological role in cell survival, angiogenesis and the immune system. However, the pathological role of Fer expression in the stromal cells surrounding renal cell carcinoma (RCC) has not been previously investigated. In the present study, immunohistochemical analysis of Fer was performed using the formalin?fixed tissue samples of 152 patients with RCC. The proliferative and apoptotic indices were used to represent the percentage of proliferation marker protein Ki?67? and cleaved caspase?3?positive cells, respectively. The microvessel density was defined as the number of cluster of differentiation (CD) 31?positively stained vessels/mm2. In addition, CD57+ and CD68+ cells were counted using semi?quantification of natural killer (NK) cells and macrophages. Fer expression in stromal cells was negatively associated with Fuhrman grade, pathological tumor stage and metastasis (P<0.001). Fer expression in stromal cells was negatively associated with CD68+ macrophage density, whereas it was positively associated with CD57+ NK cell density. Kaplan?Meier estimators indicated that decreased stromal Fer expression was a predictive marker of decreased cause?specific survival rate (P<0.001). Furthermore, low expression of Fer was identified as being an independent marker of decreased cause?specific survival using multivariate analysis (hazard ratio, 7.4; 95% confidence interval, 1.7?33.0; P<0.001). The results of the present study suggested that low Fer expression in stromal cells is associated with increased malignant aggressiveness and decreased survival in patients with RCC. CD57+ NK cell and CD68+ macrophage regulation in cancer?stromal tissue is considered to affect RCC pathology. ; 長崎大学学位論文 学位記番号:博(医歯薬)甲第847号 学位授与年月日:平成28年3月18日 ; Author: Kensuke Mitsunari, Yasuyoshi Miyata, Shin?Ichi Watanabe, Akihiro Asai, Takuji Yasuda, ...