Veterinary Pathology

Vulvo-vaginal epithelial tumors in mares: A preliminary investigation on epithelial-mesenchymal transition and tumor-immune microenvironment

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, in situ 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.

Immunohistochemical characterization of differentiation-associated transcription factors, tumor suppressor genes, and mismatch repair genes in rabbit uterine adenocarcinoma

The development of human uterine cancer is a complex process involving the abnormal expression of tumor suppressors, such as PTEN, ARID1A, and TP53; mismatch repair protein MSH6; and transcription factors, such as PAX2 and PAX8. The functional changes that lead to uterine adenocarcinoma in pet rabbits are not fully understood despite the frequent occurrence of this condition in the species. Thus, an immunohistochemical analysis was performed to visualize the protein expression pattern of carcinogenesis-related molecules in surgical biopsy specimens from 56 uterine adenocarcinomas and 8 uteruses without significant lesions in pet rabbits. Seventy percent of the adenocarcinomas were positive for estrogen receptor (ER), 7% were positive for TP53, and there was a decreased expression in comparison to control uterine epithelium for PAX2 in 54%, for PAX8 in 73%, for ARID1A in 68%, and for MSH6 in 48% of the tumors. TP53 expression was not observed in control uterine tissues. There was a significant negative correlation between nuclear ER and PAX2 immunolabeling in uterine adenocarcinomas. Heat map analysis classified samples into 4 clusters, which revealed that 1 PAX2-positive group had a higher presence of papillary-type uterine adenocarcinomas and a lower prevalence of tubular/solid types compared with the 2 PAX2-negative groups. This study demonstrated that the immunohistochemical phenotype of rabbit uterine adenocarcinoma is comparable to that of human endometrial carcinomas, suggesting the potential for similar oncogenic mechanisms that might prove useful for translational medicine research.