Ovarian cancer is associated with the highest mortality rate among gynaecologic malignancies. There is a need to refine classification of ovarian cancer and identify novel targets. The mammalian target of rapamycin (mTOR) pathway has a crucial role in the regulation of translation of specific proteins associated with ovarian cancer progression. The major downstream effectors of mTOR are eukaryotic initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase (p70S6K). We aimed to investigate the biological significance of this pathway in ovarian cancer.
Investigation of mTORC1, 4EBP1 and p70S6K protein expression, was carried out on tissue microarrays of 195 consecutive ovarian epithelial cancers treated at Nottingham University Hospitals (NUH) between 2000 and 2007. Clinicopathological and outcome data were collected.
High cytoplasmic expression of both 4EBP1 and p70S6K was associated with serous type carcinoma (p = 0.005 and p = 0.02 respectively). High expression of 4EBP1 was seen more frequently in cases treated with early debulking (p = 0.005). Univariate outcome analysis showed an inverse association between 4EBP1 expression and overall survival (p = 0.005) and development of local recurrence (p = 0.005). P70S6K showed inverse association with local recurrence (p = 0.002). High cytoplasmic expression of mTORC1 was inversely associated local recurrence (p = 0.032) and borderline significance with poor overall survival (p = 0.079).
mTORC1 and its downstream effectors, 4EBP1 and p70S6K positive expression predicts local recurrence and poor survival in ovarian cancer patients. Therefore, this could be targeted as a potential pathway that could improve patients’ survival and reduce tumour recurrence.
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All authors have declared no conflicts of interest.