title: Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.
abstract: OBJECTIVE
  Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response.
  
  
  METHODS
  Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry.
  
  
  RESULTS
  Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, p<0.001). The values for cancer specific survival were 76% and 56%, respectively (p<0.027). In the cystectomy only cohort emmprin expression was not associated with overall survival (46% vs 35%, p=0.23) or cancer specific survival (55% vs 51%, p=0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials.
  
  
  CONCLUSIONS
  Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression.
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Urology, Faculty of Medical and Health Sciences, Linköping University (SJ), Linköping, Sweden. Electronic address: tammer.hemdan@surgsci.uu.se.
authors.forename: Tammer
authors.initials: T
authors.lastname: Hemdan
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Urology, Faculty of Medical and Health Sciences, Linköping University (SJ), Linköping, Sweden.
authors.forename: Per-Uno
authors.initials: PU
authors.lastname: Malmström
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Urology, Faculty of Medical and Health Sciences, Linköping University (SJ), Linköping, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Jahnson
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Urology, Faculty of Medical and Health Sciences, Linköping University (SJ), Linköping, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Segersten
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D051926:Basigin / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002945:Cisplatin / Q000008:administration & dosage*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D015653:Cystectomy; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D000077022:Survivin; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051926:Basigin; D002945:Cisplatin; D008727:Methotrexate
keywords: CD147; antigens; biological markers; cystectomy; drug therapy; urinary bladder neoplasms