High degree of correlation between in vivo tumor oxygenation measurements and carbonic anhydrase IX tissue staining in operable human breast cancer

Abstract

678 Background: Tumor oxygenation has been shown to play an important role in determining treatment resistance. However, the use of tumor oxygenation as a predictive marker has been hindered because (1) the invasiveness and time required for in vivo oxygen measurements and (2) the inability to determine tumor oxygenation on archival tissue. This study examined the relationship between endogenous hypoxia marker (carbonic anhydrase IX; CA IX) and in vivo oxygenation measurements in breast cancer. Methods: 30 patients with operable breast cancer scheduled to undergo neoadjuvant chemotherapy/hyperthermia treatment were enrolled. In vivo tumor oxygenation was performed using Eppendorf probes. Core needle biopsies were acquired at the same time as the in vivo tumor oxygenation measurements. CA IX staining was performed using the G250 murine antihuman monoclonal antibody (gift from Dr. Oosterwijk). Angiogenesis was determined using Microvessel Density counts (MVD) obtained after JC70 monoclonal antihuman CD31 antibody staining. Results: Tumor hypoxia (median pO2 < 10 mmHg) was present in 18/30 patients (median pO2 = 3.7 mmHg). Twelve patients had well oxygenated tumors (average median pO2 = 37.1 mmHg). Tumors with positive CA IX staining had a significantly lower in vivo oxygenation measurement than those tumors with no CA IX staining (mean pO2 = 2.2 vs.8.8 mmHg; Mann-Whitney p-value=0.02). In addition, there was a correlation between MVD and CA IX expression (r=0.35; p=0.06). Conclusions: This study demonstrates a correlation between in vivo oxygenation measurements and CA IX staining in breast cancer. In addition, the correlation established between angiogenesis as measured by MVD and CA IX, and the lack of correlation between MVD and in vivo oxygenation measurements, indicates that simple detection of vessels by CD31 might not truly reflect functional vasculature. This finding might have implications for the use of MVD as a predictor in anti-angiogenesis trials, and would suggest that tumor oxygenation markers might have some predictive utility in this therapeutic setting. Supported by NIH/NCI CA42745. No significant financial relationships to disclose.