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.
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 FasLtumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis.
Authors: Jonathan M Weiss; Jeff J Subleski; Tim Back; Xin Chen; Stephanie K Watkins; Hideo Yagita; Thomas J Sayers; William J Murphy; Robert H Wiltrout Journal: J Immunol Date: 2014-05-07 Impact factor: 5.422
Authors: M E Peter; A Hadji; A E Murmann; S Brockway; W Putzbach; A Pattanayak; P Ceppi Journal: Cell Death Differ Date: 2015-02-06 Impact factor: 15.828
Authors: Tobias Luebke; Lisa Schwarz; Yan Yan Beer; Sabrina Schumann; Maria Misterek; Frida Ewald Sander; Carlos Plaza-Sirvent; Ingo Schmitz Journal: Cell Death Dis Date: 2019-05-16 Impact factor: 8.469