Expression of receptor-type tumour endothelial marker 8 in carcinoma cells showing luminal progenitor-like phenotypes in canine mammary gland carcinomas

Abstract

This study aimed to investigate the expression of receptor-type tumour endothelial marker 8 (TEM8RT) in canine mammary gland carcinomas (CMGCs) using immunohistochemistry and to evaluate the association between carcinoma cell TEM8RT expression and tumour histological features, histological grades and the differentiation status of neoplastic epithelial cells. TEM8RT expression was more frequently detected in simple carcinomas (tubular and tubulopapillary) than in solid carcinomas, and it was significantly correlated with histological grade Ⅰ tumours and a low mitotic index. Additionally, TEM8RT⁺ carcinoma cells were more frequently found in CMGCs showing luminal progenitor-like phenotypes, such as Notch1⁺, CK19⁺/CK5⁺/CD49f⁺ and CK19⁺/CK5^-/CD49f⁺. Double-labelling immunofluorescence detection techniques confirmed that most TEM8RT⁺ carcinoma cells expressed CD49f, Notch1 and CK19. However, TEM8RT immunoreactivity was not found in carcinoma cells expressing GATA3, which upregulates mature luminal cell differentiation. Furthermore, TEM8RT⁺ carcinoma cells were detected in a few CMGCs showing basal/stem cell-like phenotypes such as CK19^-/CK5⁺/CD49f⁺ and CK19^-/CK5⁺/CD49f^-. These findings indicate that TEM8RT is expressed in luminal progenitor-like carcinoma cells in CMGCs. Since TEM8 enhances self-renewal in human mammary stem/progenitor cells, it also may be involved in maintenance of luminal progenitor-like carcinoma cells, resulting in prevention of their transition to basal/stem cell-like carcinoma cells and development of less malignant CMGCs. Therefore, TEM8RT may be useful for indicating prognostic outcomes and identifying the possible ontogeny of carcinoma cells in mammary gland tumours.

Keywords: dogs; luminal progenitor; mammary gland tumour; tumour endothelial marker 8.