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. 2023 Feb 14;24(4):3853.
doi: 10.3390/ijms24043853.

Potential of uPAR, αvβ6 Integrin, and Tissue Factor as Targets for Molecular Imaging of Oral Squamous Cell Carcinoma: Evaluation of Nine Targets in Primary Tumors and Metastases by Immunohistochemistry

Mads Lawaetz  1   2 , Anders Christensen  1   2 , Karina Juhl  2 , Kirstine Karnov  1   2 , Giedrius Lelkaitis  3 , Anne-Marie Kanstrup Fiehn  3   4 , Andreas Kjaer  2 , Christian von Buchwald  1
Affiliations

Potential of uPAR, αvβ6 Integrin, and Tissue Factor as Targets for Molecular Imaging of Oral Squamous Cell Carcinoma: Evaluation of Nine Targets in Primary Tumors and Metastases by Immunohistochemistry

Mads Lawaetz et al. Int J Mol Sci. .

Abstract

No clinically approved tumor-specific imaging agents for head and neck cancer are currently available. The identification of biomarkers with a high and homogenous expression in tumor tissue and minimal expression in normal tissue is essential for the development of new molecular imaging targets in head and neck cancer. We investigated the expression of nine imaging targets in both primary tumor and matched metastatic tissue of 41 patients with oral squamous cell carcinoma (OSCC) to assess their potential as targets for molecular imaging. The intensity, proportion, and homogeneity in the tumor and the reaction in neighboring non-cancerous tissue was scored. The intensity and proportion were multiplied to obtain a total immunohistochemical (IHC) score ranging from 0-12. The mean intensity in the tumor tissue and normal epithelium were compared. The expression rate was high for the urokinase-type plasminogen activator receptor (uPAR) (97%), integrin αvβ6 (97%), and tissue factor (86%) with a median total immunostaining score (interquartile range) for primary tumors of 6 (6-9), 12 (12-12), and 6 (2.5-7.5), respectively. For the uPAR and tissue factor, the mean staining intensity score was significantly higher in tumors compared to normal epithelium. The uPAR, integrin αvβ6, and tissue factor are promising imaging targets for OSCC primary tumors, lymph node metastases, and recurrences.

Keywords: immunohistochemistry; integrin αvβ6; lymph node metastases; molecular imaging; oral squamous cell carcinoma; tissue factor; urokinase-type plasminogen activator receptor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Expression of integrin αvβ6, tissue factor, PARP-1, uPAR, VEGFR1, EpCAM, VEGFR2, Cathepsin E and integrin αvβ3 in primary tumor tissue of OSCC.
Figure 2
Figure 2
Expression of CK5 (for visualization of tumor localization), uPAR, integrin αvβ6 and tissue factor in (A) primary tumor, (B) lymph node metastases, and (C) local recurrence.
Figure 3
Figure 3
Expression of imaging targets in OSCC primary tumors.
Figure 4
Figure 4
Expression of imaging targets in OSCC lymph node metastases.
See this image and copyright information in PMC

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