Transducin-Like Enhancer of Split 3 (TLE3) Expression Is Associated with Taxane Sensitivity in Nonserous Ovarian Carcinoma in a Three-Cohort Study.
Brian Z RingRajmohan MuraliRobert A SoslowDavid D L BowtellSian FeredayAnna deFazioNadia TraficanteCatherine J KennedyAlison BrandRaghwa SharmaPaul HarnettGoli Samiminull nullPublished in: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (2018)
Background: Chemoresistance is a major challenge in ovarian cancer treatment, resulting in poor survival rates. Identifying markers of treatment response is imperative for improving outcome while minimizing unnecessary side effects. We have previously demonstrated that expression of transducin-like enhancer of split 3 (TLE3) is associated with favorable progression-free survival in taxane-treated ovarian cancer patients with nonserous histology. The purpose of this study was to perform an independent evaluation of the association of TLE3 expression with response to taxane-based chemotherapy in nonserous ovarian cancer, to validate its role as a potential therapeutic response marker for taxane-based chemotherapy.Methods: We performed immunohistochemical staining of TLE3 on ovarian cancer specimens from the Australian Ovarian Cancer Study, the Westmead Gynaecological Oncology Biobank, and Memorial Sloan Kettering Cancer Center. Progression-free survival and overall survival were assessed to validate an association between TLE3 expression and response to taxane therapy that we previously observed in a smaller study.Results: Expression of TLE3 was associated with favorable outcome only in patients who had received paclitaxel as part of their treatment regimen for both 3-year progression-free survival (n = 160; HR, 0.56; P = 0.03) and 5-year overall survival (HR, 0.53; P = 0.04). Further analysis revealed that the predictive association between TLE3 expression and outcome was strongest in tumors with clear cell histology.Conclusions: The association between high TLE3 expression and a favorable response to taxane-containing chemotherapy regimens was validated in patients with nonserous ovarian cancer.Impact: TLE3 expression may serve as a marker of chemosensitivity in taxane-treated patients with nonserous histologies. Cancer Epidemiol Biomarkers Prev; 27(6); 680-8. ©2018 AACR.