Activation of the Akt signalling pathway as a prognostic indicator in canine soft tissue sarcoma

Canine soft tissue sarcoma (STS) is relatively common in dogs and is the generic term for tumours that
originate from mesenchymal cells. While histopathological grade and immunolabelling with Ki-67 have
been used for estimating prognosis, additional indicators are needed for predicting prognosis. Aberrant
cell signalling pathways may contribute to disease activity and, therefore, prognostic markers. However,
their role in canine STS remains poorly understood. The aim of this study was to investigate expression of
phosphorylated Akt (phospho-Akt) and phosphorylated S6 (phospho-S6) as potential prognostic indicators. Immunohistochemical labelling was conducted on clinical samples of canine STS (n ¼ 67). We found that phospho-Akt expression was positively correlated with histopathological grade (P ¼ 0.001) and Ki-67 index (P <0.01). There was no apparent relationship between the type of STS and the
expression of phospho-Akt. The number of cases that expressed phospho-S6, which is the downstream
molecule of the Akt signalling pathway, was higher in immunopositive phospho-Akt cases than in
immunonegative phospho-Akt cases (P <0.0001). Furthermore, phospho-Akt expression was significantly higher in recurrent and metastatic cases. We also confirmed that phosphorylation of Akt occurred in conjunction with S6 phosphorylation in three canine STS cell lines. These results suggest that
immunolabelling for phospho-Akt, phospho-S6 and Ki-67 could potentially be used as a prognostic indicator and therapeutic target in canine STS.