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


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Article Info

DATE

2014-11-24

AUTHORS

Tove J Grönroos, Kaisa Lehtiö, Karl-Ove Söderström, Pauliina Kronqvist, Jukka Laine, Olli Eskola, Tapio Viljanen, Reidar Grénman, Olof Solin, Heikki Minn

ABSTRACT

BackgroundThe 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.ResultsNone 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).ConclusionsA 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. More... »

PAGES

876

References to SciGraph publications

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    http://scigraph.springernature.com/pub.10.1186/1471-2407-14-876

    DOI

    http://dx.doi.org/10.1186/1471-2407-14-876

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25421331


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    31 schema:description BackgroundThe 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.ResultsNone 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).ConclusionsA 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.
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    38 CD68
    39 GLUT-1
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    45 PET parameters
    46 ResultsNone
    47 VEGF
    48 account
    49 active tumor volume
    50 aggressive phenotype
    51 amount
    52 apoptosis
    53 apoptotic cells
    54 association
    55 biomarkers
    56 biopsy
    57 blood flow
    58 carcinoma
    59 cells
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    64 deoxyglucose
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    76 immunohistochemical parameters
    77 intensity
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    79 macrophage content
    80 management
    81 management of HNSCC
    82 measurements
    83 median standardized uptake value
    84 median value
    85 metabolism
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    88 p53
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    90 parameters
    91 patient outcomes
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    93 perfusion
    94 phenotype
    95 plasma ratio
    96 rate
    97 rate of apoptosis
    98 ratio
    99 relationship
    100 scale
    101 separate days
    102 significant association
    103 squamous cell carcinoma
    104 standardized uptake value
    105 tumor biopsies
    106 tumor blood flow
    107 tumor macrophage content
    108 tumor metabolism
    109 tumor volume
    110 tumors
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    112 uptake
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