title: Immunohistochemical biomarkers and FDG uptake on PET/CT in head and neck squamous cell carcinoma.
abstract: BACKGROUND
  There is an exciting complementarity between the spatial resolution provided by molecular imaging of a single, often unspecific, biomarker on one hand and the more detailed biological profile achievable from a diagnostic biopsy using a panel of immunohistochemical (IHC) markers on the other. A number of previous studies have shown a relationship between glucose transport protein expression and 18F-Fludeoxyglucose (FDG) PET uptake. Here, FDG uptake is analyzed in relation to expression of a selected panel of IHC cancer biomarkers in head and neck squamous cell carcinomas (HNSCC).
  
  
  METHODS
  IHC staining for Bcl-2, β-tubulin-1 and 2, p53, EGFR, Ki-67, glutathione-S-transferase-π and p16 was performed on formalin-fixed paraffin embedded diagnostic biopsies from 102 HNSCC cases treated at Rigshospitalet during 2005-2009. The proportion of positive cells was used for analyses, except p16, which was scored according to EORTC guidelines. In all cases, maximal FDG standardized uptake value (SUV) metrics were extracted for the primary tumor, TSUVmax. Univariate linear regression and multiple linear regression of TSUVmax versus IHC markers were performed.
  
  
  RESULTS
  In univariate analyses, TSUVmax showed negative associations with Bcl-2 (p = 0.002) and p16 (p = 0.005) indices and positive association with β-tubulin-1 index (p = 0.003). On multivariate analysis, TSUVmax remained associated with β-tubulin-1 (p = 0.009), Bcl-2 (p = 0.03) and p16 (p = 0.03). All correlations had r-squared < 0.3.
  
  
  CONCLUSIONS
  Statistically significant correlations were observed between the expression of IHC biomarkers and maximum FDG uptake in the primary tumor.
authors.affiliation: a Rigshospitalet, University of Copenhagen , Department of Oncology, Section of Radiotherapy , Copenhagen , Denmark.
authors.forename: Gregers Brünnich
authors.initials: GB
authors.lastname: Rasmussen
authors.affiliation: a Rigshospitalet, University of Copenhagen , Department of Oncology, Section of Radiotherapy , Copenhagen , Denmark.
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Vogelius
authors.affiliation: a Rigshospitalet, University of Copenhagen , Department of Oncology, Section of Radiotherapy , Copenhagen , Denmark.
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Rasmussen
authors.affiliation: f University of Maryland, Marlene and Stewart Greenebaum Cancer Center , Baltimore , Maryland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Schumaker
authors.affiliation: e University of Maryland School of Medicine , Department of Pathology , Baltimore , Maryland.
authors.forename: Olga
authors.initials: O
authors.lastname: Ioffe
authors.affiliation: f University of Maryland, Marlene and Stewart Greenebaum Cancer Center , Baltimore , Maryland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cullen
authors.affiliation: c Rigshospitalet, University of Copenhagen , Department of Clinical Physiology, Nuclear Medicine and PET , Copenhagen , Denmark.
authors.forename: Barbara Malene
authors.initials: BM
authors.lastname: Fischer
authors.affiliation: b Rigshospitalet, University of Copenhagen , Department of Pathology , Copenhagen , Denmark.
authors.forename: Marianne Hamilton
authors.initials: MH
authors.lastname: Therkildsen
authors.affiliation: a Rigshospitalet, University of Copenhagen , Department of Oncology, Section of Radiotherapy , Copenhagen , Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.affiliation: a Rigshospitalet, University of Copenhagen , Department of Oncology, Section of Radiotherapy , Copenhagen , Denmark.|d University of Maryland School of Medicine , Department of Epidemiology and Public Health , Baltimore , Maryland.|f University of Maryland, Marlene and Stewart Greenebaum Cancer Center , Baltimore , Maryland.
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005982:Glutathione Transferase / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D064847:Multimodal Imaging; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism; D049268:Positron-Emission Tomography; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed; D014404:Tubulin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019275:Radiopharmaceuticals; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D019788:Fluorodeoxyglucose F18; D005982:Glutathione Transferase; C512478:EGFR protein, human; D066246:ErbB Receptors