Real-time detection of epidermal growth factor receptor expression in fresh oral cavity biopsies using a molecular-specific contrast agent

Authors

  • Elizabeth R. Hsu,

    1. Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX
    Current affiliation:
    1. Currently a Cancer Prevention Fellow in the Cancer Prevention Fellowship Program, Division of Cancer Prevention Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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  • Ann M. Gillenwater,

    1. Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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  • M. Qasim Hasan,

    1. Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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  • Michelle D. Williams,

    1. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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  • Adel K. El-Naggar,

    1. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
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  • Rebecca R. Richards-Kortum

    Corresponding author
    1. Department of Bioengineering, Rice University, Houston, TX
    • Rice University, Department of Bioengineering, MS 142, PO Box 1892, Houston, TX 77251-1892, USA
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    • Fax: +1713-348-5877.


Abstract

Early diagnosis of individuals with high risk of developing head and neck squamous carcinoma should lead to decreased morbidity and increased survival. To aid in noninvasive early detection of oral neoplasia in vivo, we have developed a molecular-specific fluorescent contrast agent, consisting of a far-red fluorescent dye coupled to a monoclonal antibody targeted against the epidermal growth factor receptor. In our study, we used organ cultures of normal and neoplastic human oral tissue to evaluate the capabilities of using this contrast agent to enhance clinical diagnosis. Fresh tissue sections were prepared from 34 biopsies of clinically normal and abnormal oral mucosa from 17 consenting patients. Samples were exposed to contrast agent, rinsed and the presence of bound agent was detected using fluorescence confocal microscopy. Simple assays to assess cytotoxicity of the dye used in the agent and to determine labeling efficacy at physiologic temperatures were also performed. Results indicate that the mean fluorescence intensity (MFI) of samples with dysplasia and cancer are higher than that of the normal sample from the same patient, and that this increase in fluorescence could potentially be used in the early detection and delineation of premalignant lesions. Normal tissue could be distinguished from cancer or moderate dysplasia, using either the ratio of the MFI of abnormal to normal tissue or the MFI obtained from the epithelial surface. No detrimental effects from the dye were observed over a 4-day period. These results indicate that the use of this optical contrast agent could yield important clinical advantages for noninvasive early detection and molecular characterization of oral mucosa. © 2006 Wiley-Liss, Inc.

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