title: Serum carbonic anhydrase IX and its prognostic relevance in vulvar cancer.
abstract: BACKGROUND
  Therapeutic options in advanced or recurrent vulvar cancer are limited. The identification of new prognostic factors and markers for therapy stratification is therefore highly desirable. Carbonic anhydrase IX (CAIX) is up-regulated in various solid tumors and a promising new target. We therefore determined CAIX serum concentration and its prognostic relevance in correlation to intratumoral CAIX expression in patients with primary vulvar cancer.
  
  
  METHODS
  Thirty-one serum samples of patients with primary vulvar cancer were prospectively collected before surgery and analyzed for CAIX by enzyme-linked immunosorbent assay. In addition, intratumoral CAIX expression was determined by immunohistochemistry and correlation with serum CAIX and clinicopathological factors, and outcome was analyzed.
  
  
  RESULTS
  Preoperative serum concentration of CAIX ranged between 56 and 879 pg/mL (median, 147 pg/mL; mean, 237.29) and was significantly higher in patients with high intratumoral expression (median, 269 pg/mL vs 126 pg/mL, P = 0.03). High serum CAIX was not associated with any of the analyzed clinicopathological parameters. However, disease-free survival was shorter in patients with high preoperative serum CAIX (above median; P = 0.012). By immunohistochemistry, 26% of the tumors showed a moderate or strong expression of CAIX, whereas 74% showed weak or no expression. High intratumoral expression of CAIX was also associated with unfavorable disease-free survival (P = 0.043).
  
  
  CONCLUSIONS
  Carbonic anhydrase IX serum concentration is higher in patients with high intratumoral expression, and elevated preoperative serum values are associated with unfavorable prognosis. Serum CAIX might therefore be an easily assessable marker to stratify patients for adjuvant therapy and potentially monitor response. Carbonic anhydrase IX is differentially expressed in vulvar cancer and potentially associated with negative outcome.
authors.affiliation: Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lilli
authors.initials: L
authors.lastname: Kock
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.forename: Matthias
authors.initials: M
authors.lastname: Choschzick
authors.forename: Christine
authors.initials: C
authors.lastname: Eulenburg
authors.forename: Karin
authors.initials: K
authors.lastname: Milde-Langosch
authors.forename: Joerg
authors.initials: J
authors.lastname: Schwarz
authors.forename: Fritz
authors.initials: F
authors.lastname: Jaenicke
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.forename: Linn
authors.initials: L
authors.lastname: Woelber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D057234:Preoperative Period; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014846:Vulvar Neoplasms / Q000201:enzymology* / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases