title: Vascular architecture and hypoxic profiles in human head and neck squamous cell carcinomas.
abstract: Tumour oxygenation and vasculature are determinants for radiation treatment outcome and prognosis in patients with squamous cell carcinomas of the head and neck. In this study we visualized and quantified these factors which may provide a predictive tool for new treatments. Twenty-one patients with stage III-IV squamous cell carcinomas of the head and neck were intravenously injected with pimonidazole, a bioreductive hypoxic marker. Tumour biopsies were taken 2 h later. Frozen tissue sections were stained for vessels and hypoxia by fluorescent immunohistochemistry. Twenty-two sections of biopsies of different head and neck sites were scanned and analysed with a computerized image analysis system. The hypoxic fractions varied from 0.02 to 0.29 and were independent from T- and N-classification, localization and differentiation grade. No significant correlation between hypoxic fraction and vascular density was observed. As a first attempt to categorize tumours based on their hypoxic profile, three different hypoxia patterns are described. The first category comprised tumours with large hypoxic, but viable, areas at distances even greater than 200 micrometer from the vessels. The second category showed a typical band-like distribution of hypoxia at an intermediate distance (50-200 micrometer) from the vessels with necrosis at greater distances. The third category demonstrated hypoxia already within 50 micrometer from the vessels, suggestive for acute hypoxia. This method of multiparameter analysis proved to be clinically feasible. The information on architectural patterns and the differences that exist between tumours can improve our understanding of the tumour micro-environment and may in the future be of assistance with the selection of (oxygenation modifying) treatment strategies.
authors.affiliation: Institute of Radiotherapy, Department of Otorhinolaryngology, Departments of Pathology and Maxillofacial Surgery, University of Nijmegen, P.O. Box 9101, Nijmegen, HB, 6500, The Netherlands.
authors.forename: K I
authors.initials: KI
authors.lastname: Wijffels
authors.forename: J H
authors.initials: JH
authors.lastname: Kaanders
authors.forename: P F
authors.initials: PF
authors.lastname: Rijken
authors.forename: J
authors.initials: J
authors.lastname: Bussink
authors.forename: F J
authors.initials: FJ
authors.lastname: van den Hoogen
authors.forename: H A
authors.initials: HA
authors.lastname: Marres
authors.forename: P C
authors.initials: PC
authors.lastname: de Wilde
authors.forename: J A
authors.initials: JA
authors.lastname: Raleigh
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Kogel
mesh_terms: D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000098:blood supply / Q000378:metabolism; D000860:Hypoxia; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000098:blood supply / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009593:Nitroimidazoles / Q000494:pharmacology; D009959:Oropharyngeal Neoplasms / Q000098:blood supply / Q000378:metabolism; D011379:Prognosis
chemical_list: D015415:Biomarkers; D009593:Nitroimidazoles; C033815:pimonidazole