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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Main Authors: Lysanne D. A. N. de Muynck, Katja N. Gaarenstroom, Cornelis F. M. Sier, Maurice van Duijvenvoorde, Tjalling Bosse, J. Sven D. Mieog, Cornelis D. de Kroon, Alexander L. Vahrmeijer, Inge T. A. Peters
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/12/6/1562
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author Lysanne D. A. N. de Muynck
Katja N. Gaarenstroom
Cornelis F. M. Sier
Maurice van Duijvenvoorde
Tjalling Bosse
J. Sven D. Mieog
Cornelis D. de Kroon
Alexander L. Vahrmeijer
Inge T. A. Peters
author_facet Lysanne D. A. N. de Muynck
Katja N. Gaarenstroom
Cornelis F. M. Sier
Maurice van Duijvenvoorde
Tjalling Bosse
J. Sven D. Mieog
Cornelis D. de Kroon
Alexander L. Vahrmeijer
Inge T. A. Peters
author_sort Lysanne D. A. N. de Muynck
collection DOAJ
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 doaj.art-56669de2de554912b221eedf7861aed12023-11-20T03:41:06ZengMDPI AGCancers2072-66942020-06-01126156210.3390/cancers12061562Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer MetastasesLysanne D. A. N. de Muynck0Katja N. Gaarenstroom1Cornelis F. M. Sier2Maurice van Duijvenvoorde3Tjalling Bosse4J. Sven D. Mieog5Cornelis D. de Kroon6Alexander L. Vahrmeijer7Inge T. A. Peters8Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Gynecology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Gynecology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Gynecology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Gynecology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsIn 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.https://www.mdpi.com/2072-6694/12/6/1562epithelial ovarian cancer metastasessurgerytumor-targeted molecular imagingnear-infrared fluorescencebiomarkers
spellingShingle Lysanne D. A. N. de Muynck
Katja N. Gaarenstroom
Cornelis F. M. Sier
Maurice van Duijvenvoorde
Tjalling Bosse
J. Sven D. Mieog
Cornelis D. de Kroon
Alexander L. Vahrmeijer
Inge T. A. Peters
Novel Molecular Targets for Tumor-Specific Imaging of Epithelial Ovarian Cancer Metastases
Cancers
epithelial ovarian cancer metastases
surgery
tumor-targeted molecular imaging
near-infrared fluorescence
biomarkers
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 epithelial ovarian cancer metastases
surgery
tumor-targeted molecular imaging
near-infrared fluorescence
biomarkers
url https://www.mdpi.com/2072-6694/12/6/1562
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