title: Carbonic anhydrase 9 is a predictive marker of survival benefit from lower dose of bevacizumab in patients with previously treated metastatic colorectal cancer.
abstract: BACKGROUND
  Carbonic anhydrase 9 (CA9) is a marker for hypoxia and acidosis, which is linked to a poor prognosis in human tumors. The purpose of this comparative analysis was to evaluate whether CA9 and VEGF expression are associated with survival outcomes in patients with metastatic colorectal cancer (mCRC) after treatment with bevacizumab as second or later line treatment.
  
  
  METHODS
  Thirty-one mCRC patients who were treated with bevacizumab-containing chemotherapy as second or later line treatment and who had analyzable tumor paraffin blocks were selected for this study. The planned dose of bevacizumab was 5 mg/kg/2-week. Immunohistochemical (IHC) staining of CA9 and VEGF was performed and their expression was scored by the intensity multiplied by percentage of stained area.
  
  
  RESULTS
  The overall response rate was 19.4% and the disease control rate (DCR) was 61.3% with 6 partial responses and 13 cases of stable disease. The DCR was significantly higher in patients with a lower CA9 expression score compared to those with a higher score (80.0% vs. 27.3%, respectively, P = 0.004). The patients with a low CA9 expression score also showed better outcomes with regard to the median progression-free survival (P = 0.028) and overall survival (P = 0.026). However, VEGF expression was not associated with the DCR and survival.
  
  
  CONCLUSIONS
  Lower degree of CA9 expression was associated with better clinical outcomes in patients with mCRC treated with lower dose bevacizumab-based chemotherapy. Prospective studies are now needed to determine the correlation between CA9 expression and clinical outcomes after bevacizumab treatment, at different doses and in varied settings.
authors.affiliation: Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea. fahr27@gmail.com
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Hyeon Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Park
authors.forename: Hyo Seong
authors.initials: HS
authors.lastname: Choi
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Oh
authors.forename: Byung Chang
authors.initials: BC
authors.lastname: Kim
authors.forename: Dae Kyung
authors.initials: DK
authors.lastname: Sohn
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000068258:Bevacizumab; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases