An Immunohistochemical Study for Mammalian Target of Rapamycin Signaling Pathway Including Interacting PTEN in Prostatic Acinar Adenocarcinoma and Correlation with the Patient Clinicopathological Parameters

Background: The activation of AKT-mTOR-PTEN pathway may promote prostate cancer progression and affects response to targeted therapies. The full extent of this activation remains to be determined. Our aim: was to assess the expression of inactive mTOR, phosphor-mTOR, phosphor-AKT and loss of PTEN in prostatic adenocarcinomas then correlate their expression with the clinicopathological parameters. Methods: The study included 166 prostatic adenocarcinoma tissues using immunohistochemistry on tissue microarrays. Statistical analysis considering markers expression and correlation with the clinicopathologic parameters was done using appropriate tests. Result: The mean age was 72.63 and 75.9% were clinically high risk. Gleason score 7 and WHO grade group 5 were the commonest (31.3% and 31.9% respectively). Most patient (73.1%) were stage T2 or higher. Expression of inactive mTOR, phospho-mTOR and phosphor-AKT was seen in 96.1%, 93.5% and 95.9% respectively. The loss of PTEN expression was noted in 55.3%.  There were significant correlations between Gleason pattern 4 and the expression of inactive mTOR (p value <0.001 and 0.004 respectively) and phospho-mTOR (p value 0.003 and 0.001 respectively). Gleason score 7 was significantly correlated to inactive mTOR expression (p value <0.001). There was also significant correlation between phosphor-AKT and phospho- mTOR expression with p value 0.004. Conclusion: The immunohistochemical expression of inactive mTOR, phosphor-mTOR and phosphor-AKT and loss of PTEN was appreciated in most prostate cancer cases, suggesting that activation of this pathway occur early during prostate tumorigenesis. This may indicate that targeting mTOR pathway may have a promising therapeutic role in the management of prostatic adenocarcinoma.