Histometabolic Tumor Imaging of Hypoxia in Oral Cancer: Clinicopathological Correlation for Prediction of an Aggressive Phenotype

Grégoire B Morand; Martina A Broglie; Paul Schumann; Martin W Huellner; Niels J Rupp

doi:10.3389/fonc.2020.01670

Histometabolic Tumor Imaging of Hypoxia in Oral Cancer: Clinicopathological Correlation for Prediction of an Aggressive Phenotype

Front Oncol. 2020 Aug 27:10:1670. doi: 10.3389/fonc.2020.01670. eCollection 2020.

Authors

Grégoire B Morand^{1

2}, Martina A Broglie^{1

2}, Paul Schumann^{2

3}, Martin W Huellner^{2

4}, Niels J Rupp^{2

5}

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland.
² Faculty of Medicine, University of Zurich, Zurich, Switzerland.
³ Department of Cranio-Maxillo-Facial and Oral Surgery, University Hospital Zurich, Zurich, Switzerland.
⁴ Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

Abstract

Introduction: Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a widely used imaging tool for oral squamous cell carcinoma (OSCC). Preliminary studies indicate that quantification of tumor metabolic uptake may correlate with tumor hypoxia and aggressive phenotypes.

Methods: Retrospective review of a consecutive cohort of OSCC (n = 98) with available pretherapeutic FDG-PET/CT, treated at the University Hospital Zurich. Clinico-pathologico-radiological correlation between maximum standard uptake value (SUV_max) of the primary tumor, immunohistochemical staining for hypoxia-related proteins glucose transporter 1 (GLUT1) and hypoxia-inducible factor 1-alpha (HIF1a), depth of invasion (DOI), lymph node metastasis, and outcome was examined.

Results: Positive staining for GLUT1 and HIF1a on immunohistopathological analysis correlated with increased SUV_max on pretherapeutic imaging and with increased DOI (Kruskal-Wallis, P = 0.037, and P = 0.008, respectively). SUV_max and DOI showed a strong positive correlation (Spearman Rho, correlation coefficient = 0.451, P = 0.0003). An increase in SUV_max predicted nodal metastasis (Kruskal-Wallis, P = 0.017) and poor local control (log rank, P = 0.047).

Conclusion: In OSCC, FDG-PET-derived metabolic tumor parameter SUV_max serves as a surrogate marker for hypoxia and can be used to predict tumor aggressiveness, with more invasive phenotypes and poorer local control.

Keywords: carcinoma; fluorodeoxyglucose; glucose transporter type 1; lymph nodes; mouth neoplasms; positron emission tomography; squamous cell; tumor hypoxia.