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Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases

In epithelial ovarian cancer (EOC), the strongest prognostic factor is the completeness of surgery. Intraoperative molecular imaging that targets cell-surface proteins on tumor cells may guide surgeons to detect metastases otherwise not visible to the naked eye. Previously, we identified 29% more me...

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Autores principales: de Muynck, Lysanne D. A. N., Gaarenstroom, Katja N., Sier, Cornelis F. M., van Duijvenvoorde, Maurice, Bosse, Tjalling, Mieog, J. Sven D., de Kroon, Cornelis D., Vahrmeijer, Alexander L., Peters, Inge T. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352913/
https://www.ncbi.nlm.nih.gov/pubmed/32545676
http://dx.doi.org/10.3390/cancers12061562
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author de Muynck, Lysanne D. A. N.
Gaarenstroom, Katja N.
Sier, Cornelis F. M.
van Duijvenvoorde, Maurice
Bosse, Tjalling
Mieog, J. Sven D.
de Kroon, Cornelis D.
Vahrmeijer, Alexander L.
Peters, Inge T. A.
author_facet de Muynck, Lysanne D. A. N.
Gaarenstroom, Katja N.
Sier, Cornelis F. M.
van Duijvenvoorde, Maurice
Bosse, Tjalling
Mieog, J. Sven D.
de Kroon, Cornelis D.
Vahrmeijer, Alexander L.
Peters, Inge T. A.
author_sort de Muynck, Lysanne D. A. N.
collection PubMed
description In epithelial ovarian cancer (EOC), the strongest prognostic factor is the completeness of surgery. Intraoperative molecular imaging that targets cell-surface proteins on tumor cells may guide surgeons to detect metastases otherwise not visible to the naked eye. Previously, we identified 29% more metastatic lesions during cytoreductive surgery using OTL-38, a fluorescent tracer targeting folate receptor-α (FRα). Unfortunately, eleven out of thirteen fluorescent lymph nodes were tumor negative. The current study evaluates the suitability of five biomarkers (EGFR, VEGF-A, L1CAM, integrin αvβ6 and EpCAM) as alternative targets for molecular imaging of EOC metastases and included FRα as a reference. Immunohistochemistry was performed on paraffin-embedded tissue sections of primary ovarian tumors, omental, peritoneal and lymph node metastases from 84 EOC patients. Tumor-negative tissue specimens from these patients were included as controls. EGFR, VEGF-A and L1CAM were highly expressed in tumor-negative tissue, whereas αvβ6 showed heterogeneous expression in metastases. The expression of EpCAM was most comparable to FRα in metastatic lesions and completely absent in the lymph nodes that were false-positively illuminated with OTL-38 in our previous study. Hence, EpCAM seems to be a promising novel target for intraoperative imaging and may contribute to a more reliable detection of true metastatic EOC lesions.
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spelling pubmed-73529132020-07-15 Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases de Muynck, Lysanne D. A. N. Gaarenstroom, Katja N. Sier, Cornelis F. M. van Duijvenvoorde, Maurice Bosse, Tjalling Mieog, J. Sven D. de Kroon, Cornelis D. Vahrmeijer, Alexander L. Peters, Inge T. A. Cancers (Basel) Article In epithelial ovarian cancer (EOC), the strongest prognostic factor is the completeness of surgery. Intraoperative molecular imaging that targets cell-surface proteins on tumor cells may guide surgeons to detect metastases otherwise not visible to the naked eye. Previously, we identified 29% more metastatic lesions during cytoreductive surgery using OTL-38, a fluorescent tracer targeting folate receptor-α (FRα). Unfortunately, eleven out of thirteen fluorescent lymph nodes were tumor negative. The current study evaluates the suitability of five biomarkers (EGFR, VEGF-A, L1CAM, integrin αvβ6 and EpCAM) as alternative targets for molecular imaging of EOC metastases and included FRα as a reference. Immunohistochemistry was performed on paraffin-embedded tissue sections of primary ovarian tumors, omental, peritoneal and lymph node metastases from 84 EOC patients. Tumor-negative tissue specimens from these patients were included as controls. EGFR, VEGF-A and L1CAM were highly expressed in tumor-negative tissue, whereas αvβ6 showed heterogeneous expression in metastases. The expression of EpCAM was most comparable to FRα in metastatic lesions and completely absent in the lymph nodes that were false-positively illuminated with OTL-38 in our previous study. Hence, EpCAM seems to be a promising novel target for intraoperative imaging and may contribute to a more reliable detection of true metastatic EOC lesions. MDPI 2020-06-12 /pmc/articles/PMC7352913/ /pubmed/32545676 http://dx.doi.org/10.3390/cancers12061562 Text en © 2020 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
de Muynck, Lysanne D. A. N.
Gaarenstroom, Katja N.
Sier, Cornelis F. M.
van Duijvenvoorde, Maurice
Bosse, Tjalling
Mieog, J. Sven D.
de Kroon, Cornelis D.
Vahrmeijer, Alexander L.
Peters, Inge T. A.
Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases
title Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases
title_full Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases
title_fullStr Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases
title_full_unstemmed Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases
title_short Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases
title_sort novel molecular targets for tumor-specific imaging of epithelial ovarian cancer metastases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352913/
https://www.ncbi.nlm.nih.gov/pubmed/32545676
http://dx.doi.org/10.3390/cancers12061562
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