1913 WEAK EXPRESSION OF FAS LIGAND IN NEPHRECTOMIZED TUMORS PREDICTS LONG-TERM PROGRESSION-FREE SURVIVAL DURING TREATMENT BY INTERFERON Α IN METASTATIC RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Advanced (II)1 Apr 20131913 WEAK EXPRESSION OF FAS LIGAND IN NEPHRECTOMIZED TUMORS PREDICTS LONG-TERM PROGRESSION-FREE SURVIVAL DURING TREATMENT BY INTERFERON Α IN METASTATIC RENAL CELL CARCINOMA Takehiro Sejima, Hideto Iwamoto, Toshihiko Masago, Shuichi Morizane, Akihisa Yao, Tadahiro Isoyama, and Atsushi Takenaka Takehiro SejimaTakehiro Sejima Yonago, Japan More articles by this author , Hideto IwamotoHideto Iwamoto Yonago, Japan More articles by this author , Toshihiko MasagoToshihiko Masago Yonago, Japan More articles by this author , Shuichi MorizaneShuichi Morizane Yonago, Japan More articles by this author , Akihisa YaoAkihisa Yao Yonago, Japan More articles by this author , Tadahiro IsoyamaTadahiro Isoyama Yonago, Japan More articles by this author , and Atsushi TakenakaAtsushi Takenaka Yonago, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2332AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To determine the role of the immune system in patients with metastatic renal cell carcinoma (RCC), we investigated the relationship between metastatic characteristics, immunological parameters including expression of Fas ligand (FasL) in nephrectomized tumors and patient prognosis. METHODS 1) Stratification into three groups; forty-five patients with metastatic RCC had undergone nephrectomy followed by Interferon (IFN) α treatment were stratified into three groups based on the time of metastasis occurrence (i.e., at first presentation [METS at FP, n = 14], within five years of nephrectomy [early recurrence, n = 17] and five years after nephrectomy [late recurrence, n = 14]). Patient prognosis (i.e., progression-free survival [PFS] during IFN α treatment and overall survival [OS] from metastasis occurrence) and immunological parameters (i.e., neutrophil / lymphocyte ratio [NLR], serum albumin and FasL expression in RCC) were compared among the groups. FasL expression was analyzed by immunohistochemistry (IHC) and mRNA quantification. 2) Stratification into two groups; forty-five patients were stratified into two groups based on FasL positivity as determined by IHC. Patient prognosis and the aforementioned immunological parameters were compared between the groups. RESULTS 1) The patients in the late recurrence group had significantly longer PFS during IFN α treatment and OS compared to those in the other two groups. The NLR was significantly lower in the late recurrence group than in the METS at FP (P < 0.0001) and early recurrence (P = 0.0043) groups. The FasL mRNA expression was significantly lower in the late recurrence group than in the METS at FP (P = 0.0016) and early recurrence (P = 0.0076) groups. 2) The PFS during IFN α treatment was significantly longer in the FasL-negative (n = 18; median 18.4 mo.) than in the FasL-positive (n = 27; median 11.6 mo.) group (P = 0.0475). The NLR was significantly lower in the FasL-negative than in the FasL-positive group (P = 0.0085). CONCLUSIONS Our results suggest that strong host immune activity as determined by the effectiveness of IFN α treatment and OS in metastatic RCC is associated with delayed occurrence of metastasis, high peripheral blood lymphocyte activity and low FasL expression in nephrectomized tumors. “FasL counter attack” may occur in metastatic RCC; that is, FasL on the surface of circulating tumor cells binds to the Fas receptor on peripheral blood lymphocytes and diminishes the effectiveness of IFN α treatment. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e784-e785 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takehiro Sejima Yonago, Japan More articles by this author Hideto Iwamoto Yonago, Japan More articles by this author Toshihiko Masago Yonago, Japan More articles by this author Shuichi Morizane Yonago, Japan More articles by this author Akihisa Yao Yonago, Japan More articles by this author Tadahiro Isoyama Yonago, Japan More articles by this author Atsushi Takenaka Yonago, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...