510 EXCISION REPAIR CROSS-COMPLEMENTING GROUP 1 (ERCC1) MAY PREDICT THE EFFICACY OF CHEMORADIOTHERAPY FOR BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research1 Apr 2011510 EXCISION REPAIR CROSS-COMPLEMENTING GROUP 1 (ERCC1) MAY PREDICT THE EFFICACY OF CHEMORADIOTHERAPY FOR BLADDER CANCER Atsunari Kawashima, Masashi Nakayama, Yoichi Kakuta, Toyofumi Abe, Mototaka Sato, Koji Hatano, Masatoshi Mukai, Akira Nagahara, Daizo Oka, Yasutomo Nakai, Hitoshi Takayama, Toshiaki Yoshioka, Yoshihiko Hoshida, Hiroaki Itatani, Kazuo Nishimura, and Norio Nonomura Atsunari KawashimaAtsunari Kawashima Suita, Japan More articles by this author , Masashi NakayamaMasashi Nakayama Osaka, Japan More articles by this author , Yoichi KakutaYoichi Kakuta Suita, Japan More articles by this author , Toyofumi AbeToyofumi Abe Suita, Japan More articles by this author , Mototaka SatoMototaka Sato Suita, Japan More articles by this author , Koji HatanoKoji Hatano Suita, Japan More articles by this author , Masatoshi MukaiMasatoshi Mukai Suita, Japan More articles by this author , Akira NagaharaAkira Nagahara Suita, Japan More articles by this author , Daizo OkaDaizo Oka Suita, Japan More articles by this author , Yasutomo NakaiYasutomo Nakai Suita, Japan More articles by this author , Hitoshi TakayamaHitoshi Takayama Suita, Japan More articles by this author , Toshiaki YoshiokaToshiaki Yoshioka Osaka, Japan More articles by this author , Yoshihiko HoshidaYoshihiko Hoshida Osaka, Japan More articles by this author , Hiroaki ItataniHiroaki Itatani Osaka, Japan More articles by this author , Kazuo NishimuraKazuo Nishimura Osaka, Japan More articles by this author , and Norio NonomuraNorio Nonomura Suita, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1206AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chemoradiation therapy (CRT) is now widely recognized as bladder-preserving therapy for muscle-invasive bladder cancer (MIBC). However, some patients who fail CRT may miss the chance to be cured by cystectomy. Therefore, it is important to select patients with MIBC who are expected to have a good response to CRT. Several reports indicate that the excision repair cross-complementing group 1 (ERCC1) gene is associated with resistance to cisplatin and radiation therapy. In this study, we examined the correlation between ERCC1 and CRT in vitro and in vivo in bladder cancer. METHODS Bladder cancer cell lines T24, 5637, Cl8-2 (multi-drug-resistant subline of T24), and CDDP10-3 (cisplatin-resistant subline of T24) were used for in vitro assays to measure ERCC1 expression level and growth inhibition with cisplatin or irradiation (IR). To clarify the association between ERCC1 and cisplatin resistance in bladder cancer cells, we knocked down ERCC1 in Cl8-2 and CDDDP10-3 with siRNA (C18-2ΔERCC1 and CDDP10-3ΔERCC1). To further prove the cause of the radiation sensitivity of ERCC1 knockdown cells, we measured the phosphorylated histone variant H2A.X, a marker of DNA damage. In the clinical study, we then examined by immunohistochemistry whether ERCC1 nuclear staining correlates with the efficacy of CRT using cisplatin in 22 patients with MIBC. RESULTS Cl8-2 cells expressed ERCC1 mRNA 5.96-fold higher than did T24. Cl8-2 was more resistant to cisplatin or IR than was T24. Our ERCC1 knockdown experiments showed that there was statistical difference in the resistance to IR exposure not cisplatin compared with C18-2CTL and CDDP10-3CTL. C18-2ΔERCC1 and CDDP10-3ΔERCC1 recovered more slowly in terms of the number of phospho-H2A.X foci than did C18-2cont and CDDP10-3cont, suggesting continued accumulation or persistence of DSBs. In immunohistochemistry with ERCC1, six of eight positive cases did not have complete response to CRT, whereas 12 of 14 negative cases had complete response. Sensitivity and specificity were 75% and 85.7%, respectively (p = 0.008). CONCLUSIONS Our results suggest that in some bladder cancer cells, ERCC1 expression correlates with IR resistance but not with cisplatin resistance. Moreover, the lack of ERCC1 expression correlated well with the efficacy of CRT, and especially with that of IR, in our clinical study. Although further study is needed, ERCC1 expression level may predict the efficacy of CRT for MIBC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e207-e208 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Atsunari Kawashima Suita, Japan More articles by this author Masashi Nakayama Osaka, Japan More articles by this author Yoichi Kakuta Suita, Japan More articles by this author Toyofumi Abe Suita, Japan More articles by this author Mototaka Sato Suita, Japan More articles by this author Koji Hatano Suita, Japan More articles by this author Masatoshi Mukai Suita, Japan More articles by this author Akira Nagahara Suita, Japan More articles by this author Daizo Oka Suita, Japan More articles by this author Yasutomo Nakai Suita, Japan More articles by this author Hitoshi Takayama Suita, Japan More articles by this author Toshiaki Yoshioka Osaka, Japan More articles by this author Yoshihiko Hoshida Osaka, Japan More articles by this author Hiroaki Itatani Osaka, Japan More articles by this author Kazuo Nishimura Osaka, Japan More articles by this author Norio Nonomura Suita, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...