Hypoxia, blood flow and metabolism in squamous-cell carcinoma of the head and neck: correlations between multiple immunohistochemical parameters and PET.

Abstract

BACKGROUND:

The relationship between the uptake of [18F]fluoroerythronitroimidazole ([18F]FETNIM), blood flow ([15O]H2O) and 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) and immunohistochemically determined biomarkers was evaluated in squamous-cell carcinomas of the head and neck (HNSCC).

METHODS:

[18F]FETNIM and [18F]FDG PET were performed on separate days on 15 untreated patients with HNSCC. Hypoxia imaging with [18F]FETNIM was coupled with measurement of tumor blood flow using [15O]H2O. Uptake of [18F]FETNIM was measured as tumor-to-plasma ratio (T/P) and fractional hypoxic volume (FHV), and that of [18F]FDG as standardized uptake value (SUV) and the metabolically active tumor volume (TV). Tumor biopsies were cut and stained for GLUT-1, Ki-67, p53, CD68, HIF-1α, VEGFsc-152, CD31 and apoptosis. The expression of biomarkers was correlated to PET findings and patient outcome.

RESULTS:

None of the PET parameters depicting hypoxia and metabolism correlated with the expression of the biomarkers on a continuous scale. When PET parameters were divided into two groups according to median values, a significant association was detected between [18F]FDG SUV and p53 expression (p =0.029) using median SUV as the cut-off. There was a significant association between tumor volume and the amount of apoptotic cells (p =0.029). The intensity of VEGF stained cells was associated with [18F]FDG SUV (p =0.036). Patient outcome was associated with tumor macrophage content (p =0.050), but not with the other biomarkers. HIF-1α correlated with GLUT-1 (rs =0.553, p =0.040) and Ki-67 with HIF-1α (rs =506, p =0.065). p53 correlated inversely with GLUT-1 (rs = -618, p =0.019) and apoptosis with Ki-67 (rs = -638, p =0.014).

CONCLUSIONS:

A high uptake of [18F]FDG expressed as SUV is linked to an aggressive HNSCC phenotype: the rate of apoptosis is low and the expressions of p53 and VEGF are high. None of the studied biomarkers correlated with perfusion and hypoxia as evaluated with [15O]H2O-PET and [18F]FETNIM-PET. Increased tumor metabolism evaluated with PET may thus signify an aggressive phenotype, which should be taken into account in the management of HNSCC.

• Authors: Tove J Grönroos, Kaisa Lehtiö, Karl-Ove Söderström, Pauliina Kronqvist, Jukka Laine, Olli Eskola, Tapio Viljanen, Reidar Grénman, Olof Solin, Heikki Minn
• Journal: BMC cancer (BMC Cancer) Vol. 14 Pg. 876 (Nov 24 2014) ISSN: 1471-2407 [Electronic] England
• PMID: 25421331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Radiopharmaceuticals
• Fluorodeoxyglucose F18

Topics

• Biomarkers (metabolism)
• Carcinoma, Squamous Cell (diagnostic imaging, metabolism, mortality, pathology, radiotherapy)
• Fluorodeoxyglucose F18
• Head and Neck Neoplasms (diagnostic imaging, metabolism, mortality, pathology, radiotherapy)
• Humans
• Hypoxia (metabolism)
• Immunohistochemistry
• Neoplasm Grading
• Neoplasm Staging
• Neovascularization, Pathologic (diagnostic imaging, metabolism)
• Positron-Emission Tomography
• Radiopharmaceuticals
• Squamous Cell Carcinoma of Head and Neck
• Treatment Outcome
• Tumor Burden