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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MDPI AG
2020-06-01
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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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institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T19:12:03Z |
publishDate | 2020-06-01 |
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series | Cancers |
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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