Correlation between imaging and tissue biomarkers of hypoxia in squamous cell cancer of the head and neck

The aim of this study was to correlate endogenous tissue biomarkers of hypoxia with quantitative imaging parameters derived from (18)F-fluoro-misonidazole (F-MISO) and (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) and clinical outcomes in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). Tumor-tissue blocks of HNSCC patients with pretreatment F-MISO-PET/CT and FDG-PET/CT were de-archived for expression of hypoxia-inducible factor-1 alpha (HIF-1α) subunit, carbonic anhydrase-IX (CA-IX), and glucose transporter subunit-1 (GLUT-1) using immunohistochemistry (IHC). The intensity of staining was graded and correlated with quantitative imaging parameters and with disease-related outcomes. Tissue blocks were analyzed for 14 of 20 patients. On IHC, median H-scores for HIF-1α, CA-IX, and GLUT-1 were 130, 0, and 95, respectively. No significant correlation of tissue biomarkers of hypoxia with quantitative imaging parameters was found. However, borderline significant correlation was seen for H-scores of CA-IX with hypoxic tumor volume (HTV) (r = 0.873, P = 0.054) and fractional hypoxic volume (r = 0.824, P = 0.086) derived from F-MISO-PET/CT. At a median follow-up of 43 months, 5-year Kaplan–Meier estimates of locoregional control, disease-free survival, and overall survival were 53%, 43%, and 40%, respectively. Increased expression of HIF-1α or GLUT-1 (dichotomized by median H-scores) was not individually associated with disease-related outcomes. However, a combination of high HTV (>4.89cc) with above median H-scores of either HIF-1α (>130) and/or GLUT-1 (>95) was associated with worse clinical outcomes. None of the three patients with such “adverse hypoxic profile” were long-term survivors. There is no significant correlation of endogenous tissue biomarkers of hypoxia (HIF-1α, CA-IX, and GLUT-1) with quantitative imaging parameters (on F-MISO-PET/CT and FDG-PET/CT) or long-term outcomes in HNSCC. However, a combination of both can identify a subgroup of patients with adverse outcomes.