Immunohistochemical study of the PTEN/AKT pathway and the PTEN effects on E-cadherin expression in canine and feline mammary tumors

The PTEN/AKT pathway plays a key role in several biological effects such as cell metabolism, cell proliferation and cell survival. For these reason, this system is directly implicated in tumor growth and aggressiveness. Aberrant activation of this pathway is associated with several malignancies in human and veterinary medicine. The aim of this study was to investigate the role of the PTEN/AKT pathway in canine (CMTs) and feline mammary tumors (FMTs) and its influence on E-cadherin expression. Thirty-nine CMTs (7 adenomas and 32 carcinomas) and 30 feline mammary carcinomas were submitted to immunohistochemistry (IHC) to evaluate PTEN, p-AKT Ser473, Rictor and E-cadherin expression. PTEN correlated with several tumor features linked to a better biological behavior both in CMTs and FMTs, included longer survival; p-AKT Ser473 correlated with several malignant features in dogs and with a poorer prognosis both in CMTs and FMTs; Rictor correlated with lymphatic invasion in dogs and poorer prognosis in cats. Furthermore, PTEN was inversely correlated with p-AKT Ser473 expression in CMTs and FMTs and Rictor positively correlated with p-AKT Ser473 expression in both species. E-cadherin positively correlated with PTEN expression in CMTs. Our data showed a strong implication of the PTEN/AKT pathway in the progression of the CMTs and FMTs, accordingly to human literature. PTEN plays the most important role in inhibiting and controling pathway development, while p-AKT Ser473 plays a key role in increasing tumor aggressiveness. Rictor, instead, plays its oncogenic role mediating the phosphorylation of AKT in the site Serine473. PTEN correlation with E-cadherin expression in CMTs confirms the interaction of these two proteins and the influence of this pathway in the expression of adhesion proteins, as previous reported in human oncology. In conclusion, our study shows the importance of this signaling system in CMTs and FMTs and its prognostic and therapeutic implications