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VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients
BACKGROUND: Radical surgical resection of the primary tumor with mono/bilateral inguinofemoral lymph node dissection is the standard treatment for invasive vulvar squamous cell carcinoma (VSCC) and is frequently related to severe morbidity. Tailoring surgical treatment is of paramount importance, an...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026339/ https://www.ncbi.nlm.nih.gov/pubmed/35463308 http://dx.doi.org/10.3389/fonc.2022.818613 |
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author | Ravaggi, Antonella Gambino, Angela Ferrari, Federico Olivari, Alessandro Zanotti, Laura Romani, Chiara Ardighieri, Laura Antonelli, Paolo Garganese, Giorgia Gallo, Daniela Scambia, Giovanni Bignotti, Eliana Sartori, Enrico Calza, Stefano Odicino, Franco |
author_facet | Ravaggi, Antonella Gambino, Angela Ferrari, Federico Olivari, Alessandro Zanotti, Laura Romani, Chiara Ardighieri, Laura Antonelli, Paolo Garganese, Giorgia Gallo, Daniela Scambia, Giovanni Bignotti, Eliana Sartori, Enrico Calza, Stefano Odicino, Franco |
author_sort | Ravaggi, Antonella |
collection | PubMed |
description | BACKGROUND: Radical surgical resection of the primary tumor with mono/bilateral inguinofemoral lymph node dissection is the standard treatment for invasive vulvar squamous cell carcinoma (VSCC) and is frequently related to severe morbidity. Tailoring surgical treatment is of paramount importance, and a comprehensive preoperative evaluation is mandatory. Vascular endothelial growth factor D (VEGF-D) is considered a regulator of lymphangiogenesis involved in tumor spread via lymphatic vessels. The aim of this study was to evaluate the potential of VEGF-D in the prediction of inguinofemoral lymph node metastasis. METHODS: We analyzed the preoperative levels of serum VEGF-D (sVEGF-D) from two independent cohorts of patients with VSCC by enzyme-linked immunosorbent assay and its protein expression on tumor tissue by immunohistochemistry. Logistic regression was performed to identify the independent risk factors for lymph node metastasis, and Cox proportional hazard model was used for survival analysis. RESULTS: High levels of sVEGF-D, but not tissue VEGF-D, significantly correlated with positive groin nodes and a more advanced International Federation of Gynecologists and Obstetricians (FIGO) stage. In multivariable analysis, a high sVEGF-D level was an independent predictor of lymph node metastasis and worse prognosis. A prediction model based on sVEGF-D, tumor grade assessed on biopsy, tumor diameter, and lymph node clinical evaluation was able to predict lymph node metastasis, reaching C-index values of 0.79 and 0.73 in the training and validation cohorts, respectively. CONCLUSIONS: The preoperative sVEGF-D level might be a reliable biomarker for the prediction of lymph node metastasis and prognosis in patients with VSCC, supporting better clinical/surgical decision. Multicenter prospective studies are required to confirm our findings. |
format | Online Article Text |
id | pubmed-9026339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90263392022-04-23 VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients Ravaggi, Antonella Gambino, Angela Ferrari, Federico Olivari, Alessandro Zanotti, Laura Romani, Chiara Ardighieri, Laura Antonelli, Paolo Garganese, Giorgia Gallo, Daniela Scambia, Giovanni Bignotti, Eliana Sartori, Enrico Calza, Stefano Odicino, Franco Front Oncol Oncology BACKGROUND: Radical surgical resection of the primary tumor with mono/bilateral inguinofemoral lymph node dissection is the standard treatment for invasive vulvar squamous cell carcinoma (VSCC) and is frequently related to severe morbidity. Tailoring surgical treatment is of paramount importance, and a comprehensive preoperative evaluation is mandatory. Vascular endothelial growth factor D (VEGF-D) is considered a regulator of lymphangiogenesis involved in tumor spread via lymphatic vessels. The aim of this study was to evaluate the potential of VEGF-D in the prediction of inguinofemoral lymph node metastasis. METHODS: We analyzed the preoperative levels of serum VEGF-D (sVEGF-D) from two independent cohorts of patients with VSCC by enzyme-linked immunosorbent assay and its protein expression on tumor tissue by immunohistochemistry. Logistic regression was performed to identify the independent risk factors for lymph node metastasis, and Cox proportional hazard model was used for survival analysis. RESULTS: High levels of sVEGF-D, but not tissue VEGF-D, significantly correlated with positive groin nodes and a more advanced International Federation of Gynecologists and Obstetricians (FIGO) stage. In multivariable analysis, a high sVEGF-D level was an independent predictor of lymph node metastasis and worse prognosis. A prediction model based on sVEGF-D, tumor grade assessed on biopsy, tumor diameter, and lymph node clinical evaluation was able to predict lymph node metastasis, reaching C-index values of 0.79 and 0.73 in the training and validation cohorts, respectively. CONCLUSIONS: The preoperative sVEGF-D level might be a reliable biomarker for the prediction of lymph node metastasis and prognosis in patients with VSCC, supporting better clinical/surgical decision. Multicenter prospective studies are required to confirm our findings. Frontiers Media S.A. 2022-04-08 /pmc/articles/PMC9026339/ /pubmed/35463308 http://dx.doi.org/10.3389/fonc.2022.818613 Text en Copyright © 2022 Ravaggi, Gambino, Ferrari, Olivari, Zanotti, Romani, Ardighieri, Antonelli, Garganese, Gallo, Scambia, Bignotti, Sartori, Calza and Odicino https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ravaggi, Antonella Gambino, Angela Ferrari, Federico Olivari, Alessandro Zanotti, Laura Romani, Chiara Ardighieri, Laura Antonelli, Paolo Garganese, Giorgia Gallo, Daniela Scambia, Giovanni Bignotti, Eliana Sartori, Enrico Calza, Stefano Odicino, Franco VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients |
title | VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients |
title_full | VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients |
title_fullStr | VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients |
title_full_unstemmed | VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients |
title_short | VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients |
title_sort | vegf-d serum level as a potential predictor of lymph node metastasis and prognosis in vulvar squamous cell carcinoma patients |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9026339/ https://www.ncbi.nlm.nih.gov/pubmed/35463308 http://dx.doi.org/10.3389/fonc.2022.818613 |
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