Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 1512
© 2005 American Society of Clinical Oncology

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Abstract

Hypoxia-inducible factor 1alpha (HIF-1) and carbonic anhydrase IX (CA 9) expressions in glioblastoma multiform to predict response to radiation therapy

Pitie-Salpetriere Univ Hosp, AP-HP, Paris, France; Pitie-Salpetriere Hosp, Paris, France; Saint Antoine Univ Hosp, Paris, France

1512

Background: Tumor hypoxia is known to be associated with resistance to radiotherapy. Hypoxia induces the expression of hypoxia-inducible factor-1alpha (HIF-1), allowing up-regulation of the expression of downstream genes such as carbonic anhydrase IX (CA 9). Methods: We examined the expression of HIF-1 and CA 9 by immunohistochemistry in glioblastoma multiform (GBM) biopsies, and investigated their relationship with response to radiation therapy. The response to irradiation was assessed by comparing contrast-enhanced magnetic resonance images obtained before and six weeks after the completion of radiotherapy. Assessment of odds ratio were based on the logistic regression model with stepwise adjustment. The multivariate model included HIF-1 and CA 9 coded on a semi quantitative scale according to the positive tumor cell percentage (0 = no expression; + = 1–10%; ++ = 11–50%; +++ = 51–100%), and age. Results: Fifty six consecutive patients with inoperable glioblastoma treated with radiotherapy (59.4 Gy in 1.8 Gy/fraction) at the Pitie-Salpetriere hospital between 1995 and 2002, were included in this study (median age: 56 years, range, 30 to 67 years). HIF-1 was expressed in 33 of 56 (59%), and CA 9 in 38 of 52 (73%) of glioblastomas. Tumor HIF-1 expression correlated significantly with that of CA 9 (Kappa = 0.23, p = 0.003). The response rate to radiotherapy for the entire population was 29%. The expressions of HIF-1 and CA 9 were correlated inversely with the rate of response to radiotherapy (univariate analysis: HIF-1 +: odds ratio 0.21, 95% CI [0.06, 0.71], p = 0.012; CA 9 +: odds ratio 0.15, 95% CI [0.04, 0.59], p = 0.0063). The multivariate analysis showed that HIF-1 + (odds ratio 0.13, 95% CI [0.03, 0.65], p = 0.013), CA 9 +++ (odds ratio 0.21, 95% CI [0.04, 0.98], p = 0.047) and age (odds ratio 0.91, 95% CI [0.82, 0.99], p = 0.046) were independent predictors of response to radiotherapy. Conclusions: Glioblastomas with a hypoxic profile (expression of HIF-1 and/or CA 9) were associated with a significantly worse response to radiotherapy, independently of known prognostic factors. Grant from Regional PHRC: AOR 03059, Assistance Publique - Hopitaux de Paris

No significant financial relationships to disclose.

Abstract presentation from the 2005 ASCO Annual Meeting