title: Real-time detection of epidermal growth factor receptor expression in fresh oral cavity biopsies using a molecular-specific contrast agent.
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.
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, 77251, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Hsu
authors.forename: Ann M
authors.initials: AM
authors.lastname: Gillenwater
authors.forename: M Qasim
authors.initials: MQ
authors.lastname: Hasan
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Williams
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Richards-Kortum
mesh_terms: D001706:Biopsy; D003287:Contrast Media / Q000378:metabolism*; D042241:Early Diagnosis; D066246:ErbB Receptors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods*; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D008856:Microscopy, Fluorescence; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology*; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000175:diagnosis; D013696:Temperature
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D066246:ErbB Receptors