Shayan Fakurnejad1, Stan van Keulen2, Naoki Nishio3, Myrthe Engelen4, Nynke S van den Berg5, Guolan Lu6, Andrew Birkeland7, Fred Baik8, A Dimitrios Colevas9, Eben L Rosenthal10, Brock A Martin11. 1. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: shayanf@stanford.edu. 2. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States; Department of Oral and Maxillofacial Surgery, Amsterdam University Medical Center, De Boelelaan 1118, 1081 HV Amsterdam, the Netherlands. Electronic address: stanvk@stanford.edu. 3. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: nn240@stanford.edu. 4. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: mengelen@stanford.edu. 5. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: nsvdb@stanford.edu. 6. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: guolanlu@stanford.edu. 7. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: abirkela@stanford.edu. 8. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: fbaik@stanford.edu. 9. Department of Medicine, Division of Medical Oncology, University School of Medicine, 269 Campus Drive, Stanford, CA 94305, United States. Electronic address: colevas@stanford.edu. 10. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: elr@stanford.edu. 11. Department of Pathology, Stanford University School of Medicine, 291 Campus Drive, Stanford, CA 94305, United States. Electronic address: brockm@stanford.edu.
Abstract
OBJECTIVE: High-grade dysplasia is associated with a risk of malignant transformation, and it is necessary to distinguish from normal epithelium or low-grade dysplasia, especially in the intraoperative setting. We hypothesize that an anti-epidermal growth factor receptor (EGFR) contrast agent can be used to differentiate high-grade dysplasia from low-grade dysplasia and normal epithelium. MATERIALS AND METHODS: Patients with biopsy proven head and neck squamous cell carcinoma (HNSCC) were enrolled in a clinical trial using systemically injected fluorescently labeled anti-EGFR antibody (panitumumab-IRDye800CW) (NCT02415881). Paraffin embedded tumor specimens from 11 patients were evaluated by fluorescence histopathology. Hematoxylin and eosin (H&E) slides were reviewed by a board-certified pathologist, and regions of invasive squamous cell carcinoma, high-grade dysplasia and low-grade dysplasia were delineated. EGFR expression was assessed for each patient by way of immunohistochemistry. RESULTS: 11 patients were included in the study with a total of 219 areas on tissue sections analyzed; 68 normal epithelium, 53 low-grade dysplasia, 48 high-grade dysplasia, and 50 malignant regions. The signal-to-background ratio (SBR) increased proportionally with increasing grade of dysplasia; normal epithelium (1.5 ± 0.1), low-grade dysplasia (1.8 ± 0.1), high-grade dysplasia: (2.3 ± 0.2). High-grade dysplasia had a significantly higher SBR when compared to normal or low-grade dysplasia (p < 0.05). Fluorescence histopathology positively correlated with EGFR expression by immunohistochemistry, which also increased proportionally with increasing degree of dysplasia. CONCLUSION: Molecular imaging with an anti-EGFR agent can successfully discriminate high-grade dysplastic lesions from low-grade dysplasia and normal epithelium.
OBJECTIVE: High-grade dysplasia is associated with a risk of malignant transformation, and it is necessary to distinguish from normal epithelium or low-grade dysplasia, especially in the intraoperative setting. We hypothesize that an anti-epidermal growth factor receptor (EGFR) contrast agent can be used to differentiate high-grade dysplasia from low-grade dysplasia and normal epithelium. MATERIALS AND METHODS: Patients with biopsy proven head and neck squamous cell carcinoma (HNSCC) were enrolled in a clinical trial using systemically injected fluorescently labeled anti-EGFR antibody (panitumumab-IRDye800CW) (NCT02415881). Paraffin embedded tumor specimens from 11 patients were evaluated by fluorescence histopathology. Hematoxylin and eosin (H&E) slides were reviewed by a board-certified pathologist, and regions of invasive squamous cell carcinoma, high-grade dysplasia and low-grade dysplasia were delineated. EGFR expression was assessed for each patient by way of immunohistochemistry. RESULTS: 11 patients were included in the study with a total of 219 areas on tissue sections analyzed; 68 normal epithelium, 53 low-grade dysplasia, 48 high-grade dysplasia, and 50 malignant regions. The signal-to-background ratio (SBR) increased proportionally with increasing grade of dysplasia; normal epithelium (1.5 ± 0.1), low-grade dysplasia (1.8 ± 0.1), high-grade dysplasia: (2.3 ± 0.2). High-grade dysplasia had a significantly higher SBR when compared to normal or low-grade dysplasia (p < 0.05). Fluorescence histopathology positively correlated with EGFR expression by immunohistochemistry, which also increased proportionally with increasing degree of dysplasia. CONCLUSION: Molecular imaging with an anti-EGFR agent can successfully discriminate high-grade dysplastic lesions from low-grade dysplasia and normal epithelium.
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