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
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 h...
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| Veröffentlicht in: | International journal of molecular sciences 2023-02, Vol.24 (4), p.3853 |
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| creator | Lawaetz, Mads Christensen, Anders Juhl, Karina Karnov, Kirstine Lelkaitis, Giedrius Kanstrup Fiehn, Anne-Marie Kjaer, Andreas von Buchwald, Christian |
| description | 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. |
| doi_str_mv | 10.3390/ijms24043853 |
| format | Article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms24043853</identifier><identifier>PMID: 36835265</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angiogenesis ; Biomarkers ; Cell adhesion & migration ; Diagnosis ; Endothelium ; Epithelium ; Exocrine glands ; Extracellular matrix ; Head & neck cancer ; Homogeneity ; Humans ; Immunohistochemistry ; Integrins ; Lymph nodes ; Lymphatic system ; Medical imaging ; Medical prognosis ; Metastases ; Metastasis ; Molecular Imaging ; Mouth Neoplasms - diagnostic imaging ; Oral cancer ; Oral carcinoma ; Oral squamous cell carcinoma ; Patients ; Receptors, Urokinase Plasminogen Activator - metabolism ; Squamous cell carcinoma ; Squamous Cell Carcinoma of Head and Neck - diagnostic imaging ; Surgery ; Thromboplastin ; Tissue factor ; Tumors ; U-Plasminogen activator ; Urokinase ; Urokinase-Type Plasminogen Activator - metabolism</subject><ispartof>International journal of molecular sciences, 2023-02, Vol.24 (4), p.3853</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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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. 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The uPAR, integrin αvβ6, and tissue factor are promising imaging targets for OSCC primary tumors, lymph node metastases, and recurrences.</description><subject>Angiogenesis</subject><subject>Biomarkers</subject><subject>Cell adhesion & migration</subject><subject>Diagnosis</subject><subject>Endothelium</subject><subject>Epithelium</subject><subject>Exocrine glands</subject><subject>Extracellular matrix</subject><subject>Head & neck cancer</subject><subject>Homogeneity</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Integrins</subject><subject>Lymph nodes</subject><subject>Lymphatic system</subject><subject>Medical imaging</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Molecular Imaging</subject><subject>Mouth Neoplasms - diagnostic imaging</subject><subject>Oral cancer</subject><subject>Oral carcinoma</subject><subject>Oral squamous cell carcinoma</subject><subject>Patients</subject><subject>Receptors, Urokinase Plasminogen Activator - 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36835265</pmid><doi>10.3390/ijms24043853</doi><orcidid>https://orcid.org/0000-0001-6753-8129</orcidid><orcidid>https://orcid.org/0000-0003-1741-1140</orcidid><orcidid>https://orcid.org/0000-0002-2706-5547</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2023-02, Vol.24 (4), p.3853 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Angiogenesis Biomarkers Cell adhesion & migration Diagnosis Endothelium Epithelium Exocrine glands Extracellular matrix Head & neck cancer Homogeneity Humans Immunohistochemistry Integrins Lymph nodes Lymphatic system Medical imaging Medical prognosis Metastases Metastasis Molecular Imaging Mouth Neoplasms - diagnostic imaging Oral cancer Oral carcinoma Oral squamous cell carcinoma Patients Receptors, Urokinase Plasminogen Activator - metabolism Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - diagnostic imaging Surgery Thromboplastin Tissue factor Tumors U-Plasminogen activator Urokinase Urokinase-Type Plasminogen Activator - metabolism |
| title | 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 |
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