Preliminary assessment of Mesenchymal To Epithelial Transition in canine perivascular wall tumors (PWTs): E-cadherin, β-catenin and cytokeratins immunohistochemical expression

Epithelial to mesenchymal transition (EMT) has a major role in tumor progression and metastasis of carcinomas in humans and dogs. Recent findings suggest that the reverse process, mesenchymal to epithelial transition (MET), occurs in sarcomas and has been associated with decreased cell proliferation, invasion, and migration leading to a better prognosis.1 Mesenchymal cells undergoing MET acquire an epithelial-like phenotype by gaining expression of typical epithelial markers (cytokeratins, β-catenin, and E-cadherin). Studies regarding MET in canine sarcomas are scarce2 and the correlation between EMT or MET and prognosis has not been investigated fully. Canine perivascular wall tumors (PWTs) display a general more favourable behaviour compared to other soft tissue sarcomas.3 Our hypothesis is that in PWTs the development of MET phenotype may be one of the factors involved in their distinctive behaviour. Thus, the aim of this work was to explore the occurrence of MET by assessment of specific marker expression by immunohistochemistry (IHC) in canine PWTs. A series of 36 canine PWTs were routinely processed and stained with anti-pan-cytokeratin (AE1/AE3), -β-catenin, and -E-cadherin. IHC results and histologic grades were recorded for all tumors. Cases resulted grade 1 (23/38), grade 2 (12/38) and grade 3 (3/38). All cases were pan-cytokeratins negative. Nuclear and cytoplasmic expression of E-cadherin (38/38) and β-catenin (31/36) were observed. E-cadherin is involved in cell-to-cell adhesion and normally absent in normal vascular mural cells.4,5 E-cadherin and β-catenin expression may either reflect MET transition in PWTS or be indicative of a dysregulation of their corresponding pathways. [1] Yang et al. Mesenchymal to epithelial transition in sarcomas, European Journal of Cancer, 50(3):593-601, 2014. [2] Armando et al. Mesenchymal to epithelial transition driven by canine distemper virus infection of canine histiocytic sarcoma cells contributes to a reduced cell motility in vitro, Journal of Cellular and Molecular Medicine, 24(16):9332-9348, 2020. [3] Avallone et al. The controversial histologic classification of canine subcutaneous whorling tumours: The path to perivascular wall tumours, Veterinary Comparative Oncology, 18(1):3-8, 2020. [4] George et al. Cadherin:catenin complex: a novel regulator of vascular smooth muscle cell behaviour, Atherosclerosis, 188(1): 1–11, 2006. [5] Frismantiene et al. Cadherins in vascular smooth muscle cell (patho)biology: Quid nos scimus? Cellular signalling, 45: 23–42, 2018.