title: Excision repair cross-complementing group 1 may predict the efficacy of chemoradiation therapy for muscle-invasive bladder cancer.
abstract: OBJECTIVE
  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 (multidrug-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 ionizing radiation (IR). We then examined by immunohistochemistry that 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 and CDDP10-3 were more resistant to cisplatin or IR than was T24. Resistance to IR, but not to cisplatin, was removed by suppressing ERCC1 using siRNA in both Cl8-2 and CDDP10-3 cells. In immunohistochemistry with ERCC1, 6 of 8 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
  Although further study is needed, ERCC1 expression level may predict the efficacy of CRT for MIBC.
authors.affiliation: The Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsunari
authors.initials: A
authors.lastname: Kawashima
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kakuta
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Abe
authors.forename: Koji
authors.initials: K
authors.lastname: Hatano
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Mukai
authors.forename: Akira
authors.initials: A
authors.lastname: Nagahara
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nakai
authors.forename: Daizo
authors.initials: D
authors.lastname: Oka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takayama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hoshida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itatani
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishimura
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034622:RNA Interference; D011878:Radiotherapy / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin