title: Colocalization of carbonic anhydrase 9 expression and cell proliferation in human head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Tumor cells undergo a variety of biological changes under sustained hypoxic conditions, allowing cells to survive and retain their clonogenic potential. The purpose of this study is to relate the expression of the hypoxia marker carbonic anhydrase 9 (CA9) to the uptake of iododeoxyuridine (IdUrd), a marker of proliferation, in head and neck squamous cell carcinomas. Colocalization of IdUrd and CA9 may identify an important subpopulation of tumor cells that might be responsible for repopulation and disease progression.
  
  
  METHODS
  Expression of CA9, IdUrd labeling, and colocalization between IdUrd and CA9 was examined by immunohistochemistry in biopsies of head and neck squamous cell carcinomas. Biopsies were taken from 51 patients recruited between 1998 and 2001 after administration of the proliferation marker IdUrd.
  
  
  RESULTS
  A large variation was observed between the tumors in CA9 expression (range 0-39%), IdUrd labeling (range 0-81%), and colocalization between IdUrd and CA9 [FId(CA9); range 0-53%]. FId(CA9), the fraction of IdUrd-labeled cells positive for CA9, was highest at an intermediate distance from the blood vessels (100-150 microm). IdUrd labeling was higher in T4 carcinomas relative to lower stage tumors (P = 0.04). High FId(CA9) correlated with the worst disease-free survival rates (P = 0.04).
  
  
  CONCLUSIONS
  Colocalization between IdUrd labeling and CA9 expression was observed in head and neck squamous cell carcinomas, suggesting the presence of a population of tumor cells under intermediate hypoxic conditions which still has proliferative capacity. The size of this subpopulation may be indicative of tumor aggressiveness and is associated with the worst disease-free survival rates.
authors.affiliation: Department of Radiation Oncology, University Medical Center, St. Radboud, Nijmegen, The Netherlands. i.hoogsteen@rther.umcn.nl
authors.forename: Ilse J
authors.initials: IJ
authors.lastname: Hoogsteen
authors.forename: Henri A M
authors.initials: HA
authors.lastname: Marres
authors.forename: Karien I E M
authors.initials: KI
authors.lastname: Wijffels
authors.forename: Paul F J W
authors.initials: PF
authors.lastname: Rijken
authors.forename: Johannes P W
authors.initials: JP
authors.lastname: Peters
authors.forename: Franciscus J A
authors.initials: FJ
authors.lastname: van den Hoogen
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Albert J
authors.initials: AJ
authors.lastname: van der Kogel
authors.forename: Johannes H A M
authors.initials: JH
authors.lastname: Kaanders
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D001706:Biopsy; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D002277:Carcinoma / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D018572:Disease-Free Survival; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D007065:Idoxuridine / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011379:Prognosis; D013997:Time Factors
chemical_list: D000951:Antigens, Neoplasm; D019384:Nucleic Acid Synthesis Inhibitors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D007065:Idoxuridine