Expression of hypoxia-related tissue factors correlates with diminished survival of adjuvantly treated patients with chromosome 1p aberrant oligodendroglial neoplasms and therapeutic implications.
OBJECTIVE
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.


METHODS
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.
Institute of Neurology, Medical University Vienna, Vienna, Austria.
Peter
P
Birner
Matthias
M
Preusser
Ellen
E
Gelpi
Johannes
J
Berger
Brigitte
B
Gatterbauer
Inge M
IM
Ambros
Peter F
PF
Ambros
Till
T
Acker
Karl H
KH
Plate
Adrian L
AL
Harris
Johannes A
JA
Hainfellner
D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D017024:Chemotherapy, Adjuvant; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000096:biosynthesis*; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014157:Transcription Factors / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D002256:Carbonic Anhydrases; C466621:carbonic anhydrase XIV