Development of a novel contrast agent for differentiation of low grade and high grade dysplasia from normal tissue during surgery

Presentation: D004
Topic: Advanced Imaging
Type: Poster
Date: Wednesday, May 1, 2019 (1:00 PM - 7:00 PM) | Thursday, May 2, 2019 (9:00 AM - 7:00 PM)
Session: Wednesday, May 1, 2019 (1:00 PM - 7:00 PM) | Thursday, May 2, 2019 (9:00 AM - 7:00 PM)
Authors: Shayan Fakurnejad, BS, Stan van Keulen, MD, Nynke S van den Berg, PhD, Guolan Lu, PhD, Andrew Birkeland, MD, Brock Martin, MD, Eben Rosenthal, MD
Institution(s): Stanford University

Importance: It is known that high-grade dysplasia has an increased risk of malignant transformation when compared to normal or low-grade dysplasia. However, low-grade and high-grade dysplasia are histological definitions and cannot be differentiated by physical exam. We have developed a systemically injected fluorescent contrast agent that can differentiate dysplastic and malignant tissue based on differences in EGFR expression.

Objective: To determine if differences in EGFR expression can help discriminate low-grade from high-grade dysplasia from normal tissue in patients with head and neck squamous cell carcinoma (HNSCC).

Methods: We analyzed tumor specimens obtained from patients with HNSCC who were enrolled in a clinical trial assessing the efficacy of fluorescently labeled anti-EGFR antibody (panitumumab-IRDye800CW) as a fluorescent contrast agent (NCT02415881). Fluorescence images were obtained at the time of and following surgery and then fluorescence intensity was correlated with pathology. H&E stained slides were reviewed by a board-certified pathologist to delineate regions of invasive squamous cell carcinoma, high-grade dysplasia, and low-grade dysplasia, which was subsequently correlated with the fluorescence imaging.

Results: A total of 24 patients were included in the study, of which 11 were selected for further analysis of invasive squamous cell carcinoma, high-grade dysplasia, and low-grade dysplasia. We analyzed separate tissue sections from these patient specimens which allowed analysis of 44 normal, 38 low-grade dysplasia, 42 high-grade dysplasia, and 32 invasive SCC separate sections. We found that the intensity of fluorescence (measured as mean fluorescence intensity (MFI)) increased with the grade of dysplasia; normal mucosa (1.7 MFI), low-grade dysplasia (3.4 MFI), high-grade dysplasia (4.0 MFI). Low-grade dysplasia and high-grade dysplasia had significantly greater signal-to-noise ratio when compared to normal (p<0.05), and high-grade was distinguishable from low-grade dysplasia (p<0.05). This corresponded to increasing EGFR expression with increasing degree of dysplasia on IHC staining of consecutive slides.

Conclusions: We identified a novel fluorescent agent in clinical trials (Panitumumab-IRDye800CW) that can successfully discriminate low-grade and high-grade dyplasia lesions from normal tissue intra-operatively.