Clinical and outcome significance of positive AKT expression in epithelial ovarian cancer


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M L Alabdullah1,A Alblihy2,P Moseley3,S Madhusudan3,S Chan3,E Rakha2
1university of nottingham,2University of Nottingham,3Nottingham University Hospitals

Abstract

Background

Ovarian cancer (OC) is the third most common gynaecological cancer among women worldwide and it is associated with the highest mortality rate among gynaecologic malignancies. OC is heterogeneous disease and affected by multiple epigenetic and genetic factors. A major reason for the lack of success in effectively eradicating OC can be due to the complex interconnected signalling networks coupled with the distinctive tumour microenvironment. There is an urgent need to refine classification of ovarian cancer and identify novel targets. The PI3K/AKT/mTOR pathway is an intracellular signalling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation and cancer. We aimed to investigate the prognostic role of AKT in ovarian cancer.

Method

Investigation of the expression of AKT in ovarian epithelial cancer was carried out on tissue microarrays of 525 consecutive ovarian epithelial cancer cases treated at Nottingham University Hospitals (NUH) between 1997 and 2010 and their expression was correlated to clinicopathological outcomes as well as to recurrence free survival (RFS).

Results

High cytoplasmic AKT expression was significantly associated with serous type of tumour (p = 0.042) and poor outcome in terms of Recurrence Free Survival (RFS) (P=0.034). Moreover, by selecting only stage one disease high AKT expression was significantly correlated with worse recurrence outcome (P=0.038) and higher chance of residual tumour following surgery (P=0.049). In Mucinous tumour subtype, a higher chance of resistance to platinum chemotherapy was in borderline significance with high AKT expression (P=0.062). In addition in Endometroid tumours, high AKT expression showed a significant higher chance of residual tumour following surgery (P=0.045).

Conclusion

AKT protein is a prospectively valuable recurrence predictive biomarker of epithelial ovarian cancer. Furthermore, it could be used as a future target in OC management.