Fas Expression in Renal Cell Carcinoma Accurately Predicts Patient Survival after Radical Nephrectomy

被引:16
作者
Sejima, Takehiro [1 ]
Morizane, Shuichi [1 ]
Hinata, Nobuyuki [1 ]
Yao, Akihisa [1 ]
Isoyama, Tadahiro [1 ]
Saito, Motoaki [2 ]
Takenaka, Atsushi [1 ]
机构
[1] Tottori Univ, Div Urol, Dept Surg, Fac Med, Yonago, Tottori 6838504, Japan
[2] Tottori Univ, Div Mol Pharmacol, Dept Pathophysiol & Therapeut Sci, Fac Med, Yonago, Tottori 6838504, Japan
关键词
Apoptosis; Renal cell carcinoma; Nephrectomy; Prognostic factors; TUMOR IMMUNE EVASION; CANCER IN-VIVO; LIGAND EXPRESSION; BCL-2; APOPTOSIS; DEATH; COUNTERATTACK; CYTOTOXICITY; MECHANISMS; PATHWAYS;
D O I
10.1159/000334453
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Objectives: To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs). Patients and Methods: mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models. Results: A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator. Conclusions: The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis. Copyright (C) 2012 S. Karger AG, Basel
引用
收藏
页码:263 / 270
页数:8
相关论文
共 27 条
[1]  
Bennett MW, 1998, J IMMUNOL, V160, P5669
[2]   CD95 promotes tumour growth [J].
Chen, Lina ;
Park, Sun-Mi ;
Tumanov, Alexei V. ;
Hau, Annika ;
Sawada, Kenjiro ;
Feig, Christine ;
Turner, Jerrold R. ;
Fu, Yang-Xin ;
Romero, Iris L. ;
Lengyel, Ernst ;
Peter, Marcus E. .
NATURE, 2010, 465 (7297) :492-496
[3]  
COHEN JJ, 1992, ANNU REV IMMUNOL, V10, P267, DOI 10.1146/annurev.iy.10.040192.001411
[4]   Where have all the T cells gone? Mechanisms of immune evasion by tumors [J].
Finke, J ;
Ferrone, S ;
Frey, A ;
Mufson, A ;
Ochoa, A .
IMMUNOLOGY TODAY, 1999, 20 (04) :158-160
[5]  
FISHER TC, 1993, CANCER RES, V53, P3321
[6]   BCL-2 IS AN INNER MITOCHONDRIAL-MEMBRANE PROTEIN THAT BLOCKS PROGRAMMED CELL-DEATH [J].
HOCKENBERY, D ;
NUNEZ, G ;
MILLIMAN, C ;
SCHREIBER, RD ;
KORSMEYER, SJ .
NATURE, 1990, 348 (6299) :334-336
[7]   Expression of Fas in renal cell carcinoma [J].
Horie, S ;
Kano, M ;
Higashihara, E ;
Moriyama, N ;
Tanaka, E ;
Hirose, A ;
Kakizoe, T ;
Kawabe, K .
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 1997, 27 (06) :384-388
[8]   Tumor counterattack: fact or fiction? [J].
Igney, FH ;
Krammer, PH .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2005, 54 (11) :1127-1136
[9]   Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy [J].
Karam, Jose A. ;
Lotan, Yair ;
Karakiewicz, Pierre I. ;
Ashfaq, Raheela ;
Sagalowsky, Arthur I. ;
Roehrborn, Claus G. ;
Shariat, Shahrokh F. .
LANCET ONCOLOGY, 2007, 8 (02) :128-136
[10]   Human and Mouse Colon Cancer Utilizes CD95 Signaling for Local Growth and Metastatic Spread to Liver [J].
Li, Hanchen ;
Fan, Xueli ;
Stoicov, Calin ;
Liu, Jan Hua ;
Zubair, Sharif ;
Tsai, Elena ;
Ste Marie, Ronald ;
Wang, Timothy C. ;
Lyle, Stephen ;
Kurt-Jones, Evelyn ;
Houghton, Jeanmarie .
GASTROENTEROLOGY, 2009, 137 (03) :934-944