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PURPOSE: Oligodendroglial neoplasms with chromosome 1p deletion are chemosensitive, and stratified adjuvant therapies have been proposed on the basis of 1p status. In this study, we evaluated expression of hypoxia-related factors and its influence on survival in oligodendroglial brain tumors with chromosome 1p aberrations. EXPERIMENTAL DESIGN: Forty-four primary and 16 recurrent oligodendroglial neoplasms with 1p aberrations (deletion or imbalance) were investigated immunohistochemically for expression of hypoxia-inducible factor 1alpha and carbonic anhydrase-9. We used in situ hybridization to investigate expression of vascular endothelial growth factor-mRNA. We defined as "low hypoxia score" expression of no or only one marker and as "high hypoxia score" expression of two or three markers. The predominant vascular patterns of tumors were defined as classic or bizarre vascular formations, based on anti-CD34-immunostaining. RESULTS: High hypoxia score was evident in 16 of 44 (36.4%) primary tumor specimens and in 14 of 16 (87.5%) recurrent tumors (P = 0.001). High hypoxia score was associated with the presence of bizarre vascular proliferations and WHO grade III. In the subgroup of patients who received adjuvant therapy, univariate analysis showed significantly shorter survival of patients with high hypoxia score (n = 27; P = 0.0145). For all of the primary tumors, hypoxia score was an independent prognostic factor (P = 0.045). CONCLUSIONS: A fraction of oligodendroglial neoplasms with 1p aberrations shows evidence of tissue hypoxia, which significantly influences survival of patients receiving adjuvant therapy. Evaluation of tissue hypoxia could become useful for recruitment of patients for individualized therapy strategies, e.g., selection of patients with hypoxic tumors for hyperbaric oxygenation preceding radiotherapy.

Original publication

DOI

10.1158/1078-0432.CCR-04-0617

Type

Journal article

Journal

Clin cancer res

Publication Date

01/10/2004

Volume

10

Pages

6567 - 6571

Keywords

Adult, Brain Neoplasms, Carbonic Anhydrases, Chemotherapy, Adjuvant, Chromosome Deletion, Chromosomes, Human, Pair 1, DNA-Binding Proteins, Female, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Immunohistochemistry, In Situ Hybridization, In Situ Hybridization, Fluorescence, Male, Middle Aged, Neoplasm Recurrence, Local, Nuclear Proteins, Oligodendroglioma, RNA, Messenger, Survival Analysis, Transcription Factors, Vascular Endothelial Growth Factor A