EGFR and αvβ6 as Promising Targets for Molecular Imaging of Cutaneous and Mucosal Squamous Cell Carcinoma of the Head and Neck Region.

Victor M Baart,Cornelis F M Sier,Sylvia L Van Egmond,Willem A Dijckmeester,Chayenne Van Duijn,Jeroen C Jansen,Danielle Cohen,Alexander L Vahrmeijer

doi:10.3390/cancers12061474

Victor M Baart, Cornelis F M Sier + Show 6 more

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https://doi.org/10.3390/cancers12061474

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Journal: Cancers	Publication Date: Jun 5, 2020
Citations: 18	License type: CC BY 4.0

Affiliation: Leiden University Medical Center

Abstract

R0 resection is paramount in cutaneous squamous cell carcinoma (CSCC) and head and neck squamous cell carcinoma (HNSCC). However, in the setting of recurrence, immunocompromised patients, or non-keratinizing squamous cell carcinoma (SCC) with a spindle growth pattern, tumor borders are difficult, if not impossible, to determine. Fluorescence-guided surgery (FGS) aids in this differentiation. Potential targets for FGS of CSCC and HNSCC were evaluated. Most sections stained intensely for αvβ6 and epidermal growth factor receptor (EGFR) on tumor cells. Normal epithelium stained less for αvβ6 than for EGFR. In addition, soft tissue and stroma stained negative for both, allowing for clear discrimination of the soft tissue margin. Tumor cells weakly expressed urokinase plasminogen activator receptor (uPAR) while expression on stromal cells was moderate. Normal epithelium rarely expressed uPAR, resulting in clear discrimination of superficial margins. Tumors did not consistently express integrin β3, carcinoembryonic antigen, epithelial cell adhesion molecule, or vascular endothelial growth factor A. In conclusion, αvβ6 and EGFR allowed for precise discrimination of SSC at the surgically problematic soft tissue margins. Superficial margins are ideally distinguished with uPAR. In the future, FGS in the surgically challenging setting of cutaneous and mucosal SCC could benefit from a tailor-made approach, with EGFR and αvβ6 as targets.

Highlights

Margins are tumor-positive in 6.3–12.8% of tumor resections of cutaneous and mucosal squamous cell carcinomas (SCCs) of the head and neck region [1,2]
As the compromised patients represent an important group of high-risk cases, a sub-group analysis was performed with the three most promising biomarkers to determine whether immunosuppression altered biomarker expression
Αvβ6 and epidermal growth factor receptor (EGFR) allowed for the precise discrimination of SSC at the often more problematic soft tissue margins in Cutaneous squamous cell carcinoma (CSCC) and head and neck squamous cell carcinoma (HNSCC)

Summary

Introduction

Margins are tumor-positive in 6.3–12.8% of tumor resections of cutaneous and mucosal squamous cell carcinomas (SCCs) of the head and neck region [1,2]. In the setting of recurrence after previous R1 resection or irradiation, immunocompromised patients, or non-keratinizing SCC with a spindle growth pattern, tumor borders are difficult, if not impossible, to determine. In these high-risk cases, irradical resection rates can be up to 60% and local recurrence rates as high as 50% [2,3]. Recurrence rates can exceed 50% in patients with high risk factors, such as head andneck localization, perineural involvement, or immunosuppression [3,5,6,7] In all these cases, local control by achieving tumor-free margins is paramount in decreasing the risk for metastasis and recurrence [8]

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