Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy.
BACKGROUND
Customizing chemotherapy on the basis of chemosentitivity prediction may improve outcome in advanced bladder cancer patients. Since DNA damaging agents are the cornerstones of therapy, we hypothesized that levels of DNA repair genes could predict survival.


METHODS
Messenger RNA expression levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT-PCR in tumor DNA from 57 advanced and metastatic bladder cancer patients treated with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol). Levels were correlated with survival, time to disease progression and chemotherapy response.


RESULTS
Median survival was significantly higher in patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow-up 19 months). A trend towards longer time to progression was observed in patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1 and caveolin-1, however, failed to predict the survival and a clear link with chemotherapy response could not be established. On multivariate analysis with pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for survival.


CONCLUSIONS
The results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy.
Bellmunt
J
J
Vall d'Hebron University Hospital, Barcelona, Spain. jbellmunt@imas.imim.es
Paz-Ares
L
L
Cuello
M
M
Cecere
F L
FL
Albiol
S
S
Guillem
V
V
Gallardo
E
E
Carles
J
J
Mendez
P
P
de la Cruz
J J
JJ
Taron
M
M
Rosell
R
R
Baselga
J
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000032:analysis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D051242:Caveolin 1 / Q000032:analysis / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D019992:Databases as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004720:Endonucleases / Q000032:analysis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D012262:Ribonucleoside Diphosphate Reductase; D013997:Time Factors; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000093542:Gemcitabine
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D051242:Caveolin 1; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine