Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications

Abstract Although the immunohistochemical expression of the transmembrane sialoglycoprotein podoplanin (D2-40) has been repeatedly reported as a factor of prognosis in various tumor entities—its potential prognostic relevance in squamous cell carcinomas of the vulva remains to be evaluated. In the p...

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Main Authors: Gilbert Georg Klamminger, Meletios P. Nigdelis, Annick Bitterlich, Mariam Parvanta, Martin Ertz, Laura Schnöder, Bernd Holleczek, Roxana Schwab, Annette Hasenburg, Bashar Haj Hamoud, Erich Franz Solomayer, Mathias Wagner
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-06908-8
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author Gilbert Georg Klamminger
Meletios P. Nigdelis
Annick Bitterlich
Mariam Parvanta
Martin Ertz
Laura Schnöder
Bernd Holleczek
Roxana Schwab
Annette Hasenburg
Bashar Haj Hamoud
Erich Franz Solomayer
Mathias Wagner
author_facet Gilbert Georg Klamminger
Meletios P. Nigdelis
Annick Bitterlich
Mariam Parvanta
Martin Ertz
Laura Schnöder
Bernd Holleczek
Roxana Schwab
Annette Hasenburg
Bashar Haj Hamoud
Erich Franz Solomayer
Mathias Wagner
author_sort Gilbert Georg Klamminger
collection DOAJ
description Abstract Although the immunohistochemical expression of the transmembrane sialoglycoprotein podoplanin (D2-40) has been repeatedly reported as a factor of prognosis in various tumor entities—its potential prognostic relevance in squamous cell carcinomas of the vulva remains to be evaluated. In the present study, we evaluated 68 patients with primary vulvar carcinomas (VC) and analyzed the cytoplasmic/membranous immunohistochemical expression of podoplanin in viable tumor cells and cancer-associated fibroblasts (CAFs) within the adjacent peritumoral stroma. To determine potential associations between podoplanin expression and traditional clinicopathological parameters (e.g., tumor stage, infiltration depth, groin lymph node metastasis), as well as with local recurrences, metastases, and patient’s overall survival, subsequent data analysis was conducted using Spearman correlation analysis, Fisher’s exact test and the log-rank test (Mantel-Cox). Although our results did not substantiate a positive correlation of podoplanin expression in tumor cells or CAFs with traditional histomorphological parameters, we propose a prognostic potential of podoplanin as a tissue-based biomarker in HPV-associated VC. In our exploratory pilot study, we observed a significantly improved overall survival in this distinct subgroup (Log-rank (Mantel-Cox) test; p = 0.0399). The results of our retrospective study may support the expectations that podoplanin, a common and widely available antibody, could be used as a tool for prognostic purposes in the future. Further research and validation are necessary before these markers can be implemented in clinical practice.
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spelling doaj-art-684cd4007c5e47bdb27caa3cbb44c0502025-08-20T03:22:49ZengNature PortfolioScientific Reports2045-23222025-06-011511810.1038/s41598-025-06908-8Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implicationsGilbert Georg Klamminger0Meletios P. Nigdelis1Annick Bitterlich2Mariam Parvanta3Martin Ertz4Laura Schnöder5Bernd Holleczek6Roxana Schwab7Annette Hasenburg8Bashar Haj Hamoud9Erich Franz Solomayer10Mathias Wagner11Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS)Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center (UKS)Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS)Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS)Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS)Saarland University Medical Center for Tumor Diseases (UTS)Saarland Cancer RegistryDepartment of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University MainzDepartment of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University MainzDepartment of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center (UKS)Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center (UKS)Department of General and Special Pathology, Saarland University (USAAR) and Saarland University Medical Center (UKS)Abstract Although the immunohistochemical expression of the transmembrane sialoglycoprotein podoplanin (D2-40) has been repeatedly reported as a factor of prognosis in various tumor entities—its potential prognostic relevance in squamous cell carcinomas of the vulva remains to be evaluated. In the present study, we evaluated 68 patients with primary vulvar carcinomas (VC) and analyzed the cytoplasmic/membranous immunohistochemical expression of podoplanin in viable tumor cells and cancer-associated fibroblasts (CAFs) within the adjacent peritumoral stroma. To determine potential associations between podoplanin expression and traditional clinicopathological parameters (e.g., tumor stage, infiltration depth, groin lymph node metastasis), as well as with local recurrences, metastases, and patient’s overall survival, subsequent data analysis was conducted using Spearman correlation analysis, Fisher’s exact test and the log-rank test (Mantel-Cox). Although our results did not substantiate a positive correlation of podoplanin expression in tumor cells or CAFs with traditional histomorphological parameters, we propose a prognostic potential of podoplanin as a tissue-based biomarker in HPV-associated VC. In our exploratory pilot study, we observed a significantly improved overall survival in this distinct subgroup (Log-rank (Mantel-Cox) test; p = 0.0399). The results of our retrospective study may support the expectations that podoplanin, a common and widely available antibody, could be used as a tool for prognostic purposes in the future. Further research and validation are necessary before these markers can be implemented in clinical practice.https://doi.org/10.1038/s41598-025-06908-8
spellingShingle Gilbert Georg Klamminger
Meletios P. Nigdelis
Annick Bitterlich
Mariam Parvanta
Martin Ertz
Laura Schnöder
Bernd Holleczek
Roxana Schwab
Annette Hasenburg
Bashar Haj Hamoud
Erich Franz Solomayer
Mathias Wagner
Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications
Scientific Reports
title Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications
title_full Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications
title_fullStr Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications
title_full_unstemmed Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications
title_short Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications
title_sort evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications
url https://doi.org/10.1038/s41598-025-06908-8
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