title: Molecular biomarkers for advanced renal cell carcinoma: implications for prognosis and therapy.
abstract: OBJECTIVE
  The aim of this study was to determine reliable predictive biomarkers for patients with metastatic renal cell carcinomas (RCCs) who had received cytokine therapy.
  
  
  METHODS
  Tissue specimens were obtained from 62 patients with metastatic RCCs between 1995 and 2006. Paraffin wax embedded tissues were immunostained for carbonic anhydrase IX (CAIX), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF).
  
  
  RESULTS
  Fifty-two specimens (84%) were assessed as clear cell type, with 5, 3, and 2 tumors showing sarcomatoid, papillary, and undifferentiated features, respectively. With a median 54 months of follow-up, 15/18 responding patients (83%) exhibited high CAIX staining compared with only 24/44 (55%) nonresponding patients (odds ratio, OR, 4.1; 95% confidence interval, CI 1.1-16.5, P = 0.04). There was a positive correlation between maximal COX-2 intensity and response for cytokine therapy (Spearman test P = 0.001; rho = 0.408). Corrected calcium level < or = 10 mg/dl (hazard ratio, HR, 0.1; 95% CI 0.15-0.28; P < 0.001), normal hemoglobin level (HR 0.30; 95% CI 0.15-0.50; P = 0.001), and COX-2 expression > or = 50% (HR 0.33; 95% CI 0.15-0.70; P = 0.008) were significant predictive factors of prolonged overall survival.
  
  
  CONCLUSIONS
  Thus, COX-2 and CAIX seem to be important predictors of outcome in patients with metastatic RCCs and might enhance the prognostic information obtained from pathology specimens.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyo Song
authors.initials: HS
authors.lastname: Kim
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Han Yong
authors.initials: HY
authors.lastname: Choi
authors.forename: Hyun Moo
authors.initials: HM
authors.lastname: Lee
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Jeon
authors.forename: Hongil
authors.initials: H
authors.lastname: Ha
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Hwang
authors.forename: Seungkoo
authors.initials: S
authors.lastname: Lee
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases