Abstract: Vulvo-vaginal epithelial tumors are uncommon in mares, and data on the epithelial-to-mesenchymal transition (EMT) and the tumor-immune microenvironment (TIME) are still lacking. This is a study investigating the equus caballus papillomavirus type 2 (EcPV2) infection state as well as the EMT process and the tumor microenvironment in vulvo-vaginal preneoplastic/ benign (8/22) or malignant (14/22) epithelial lesions in mares. To do this, histopathological, immunohistochemical, transcriptomic, hybridization, and correlation analyses were carried out. Immunohistochemistry quantification showed that cytoplasmic E-cadherin and β-catenin expression as well as nuclear β-catenin expression were features of malignant lesions, while benign/preneoplastic lesions were mainly characterized by membranous E-cadherin and β-catenin expression. Despite this, there were no differences between benign and malignant equine vulvo-vaginal lesions in the expression of downstream genes involved in the canonical and noncanonical wnt/β-catenin pathways. In addition, malignant lesions were characterized by a lower number of cells with cytoplasmic cytokeratin expression as well as a slightly higher cytoplasmic vimentin immunolabeling. The TIME of malignant lesions was characterized by more numerous CD204 M2-polarized macrophages. Altogether, our results support the hypothesis that some actors in TIME such as CD204 M2-polarized macrophages may favor the EMT process in equine vulvo-vaginal malignant lesions providing new insights for future investigations in the field of equine EcPV2-induced genital neoplastic lesions.
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This research examines vulvo-vaginal epithelial tumors in horses, looking specifically at the process known as epithelial-to-mesenchymal transition (EMT) and the environment within these tumors. Notably, it explores the implication of equine papillomavirus, the expressions of certain proteins, and the infiltration of immune cells in benign and malignant tumors, providing fresh insights into this understudied field.
Research Focus and Methodology
The study investigates uncommon vulvo-vaginal epithelial tumors in horses, specifically analyzing elements such as EMT and the tumor-immune microenvironment (TIME).
The researchers primarily focused on the role of the equus caballus papillomavirus type 2 (EcPV2) infection and its link to this type of cancer.
Various methods like histopathological, immunohistochemical, transcriptomic, hybridization, and correlation analyses are used for this research to get a holistic understanding of the condition.
Findings on EMT and Cell Expression
The malignancy of the lesions was associated with the cytoplasmic expression of E-cadherin and β-catenin, and nuclear β-catenin expression. Membranous E-cadherin and β-catenin expression were associated with benign or potentially cancerous lesions.
Interestingly, no distinct differences were identified between benign and malignant vulvo-vaginal lesions in horses in the expression of genes related to canonical and noncanonical wnt/β-catenin pathways.
More malignant lesions were characterized by fewer cells showing cytoplasmic cytokeratin expression and slightly more showing cytoplasmic vimentin immunolabeling.
Understanding the Tumor-Immune Microenvironment
The researchers found the microenvironment of malignant lesions to be associated with more CD204 M2-polarized macrophages—immune cells that play a role in immune regulation.
This suggests that these macrophages might be enhancing the EMT process in these malignant vulvo-vaginal lesions in horses.
Implications of the Findings
These findings underline the potential complexity involved in the progression of vulvo-vaginal epithelial tumors in horses.
The role of the virus, EcPV2, as well as the involvement of immune cells like the CD204 M2-polarized macrophages in the progression of the disease could spur new avenues of research.
The study also shows that while expression of certain proteins may differ between benign and malignant lesions, changes in associated gene expression may not be as clear-cut, implying a multilevel regulation of the disease.
Cite This Article
APA
Armando F, Porcellato I, de Paolis L, Mecocci S, Passeri B, Ciurkiewicz M, Mechelli L, Grazia De Ciucis C, Pezzolato M, Fruscione F, Brachelente C, Montemurro V, Cappelli K, Puff C, Baumgärtner W, Ghelardi A, Razzuoli E.
(2023).
Vulvo-vaginal epithelial tumors in mares: A preliminary investigation on epithelial-mesenchymal transition and tumor-immune microenvironment.
Vet Pathol, 3009858231207025.
https://doi.org/10.1177/03009858231207025
University of Veterinary Medicine Hannover, Hannover, Germany.
Porcellato, Ilaria
University of Perugia, Perugia, Italy.
de Paolis, Livia
University of Perugia, Perugia, Italy.
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, Genova, Italy.
Mecocci, Samanta
University of Perugia, Perugia, Italy.
Passeri, Benedetta
University of Parma, Parma, Italy.
Ciurkiewicz, Małgorzata
University of Veterinary Medicine Hannover, Hannover, Germany.
Mechelli, Luca
University of Perugia, Perugia, Italy.
Grazia De Ciucis, Chiara
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, Genova, Italy.
University of Pavia, Pavia, Italy.
Pezzolato, Marzia
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, Genova, Italy.
Fruscione, Floriana
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, Genova, Italy.
Brachelente, Chiara
University of Perugia, Perugia, Italy.
Montemurro, Vittoria
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, Genova, Italy.
Cappelli, Katia
University of Perugia, Perugia, Italy.
Puff, Christina
University of Veterinary Medicine Hannover, Hannover, Germany.
Baumgärtner, Wolfgang
University of Veterinary Medicine Hannover, Hannover, Germany.
Ghelardi, Alessandro
Ospedale Apuane, Massa, Italy.
Razzuoli, Elisabetta
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D'Aosta, Genova, Italy.
Conflict of Interest Statement
Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.