Abstract
We have previously shown that transducin-like enhancer of split 3 (TLE3) is associated with outcome specifically in patients with taxane-treated breast cancer and not in patients treated with anthracycline-based regimens without a taxane. The purpose of this study was to assess the association between TLE3 expression and recurrence in patients with ovarian carcinoma treated with a taxane containing regimen as opposed to those treated with a platinum-based agent alone. We carried out immunohistochemical staining of TLE3 in two series of ovarian cancer specimens from the University of Alabama at Birmingham, Birmingham, AL and the Royal Hospital for Women, Sydney, Australia. Local and distant recurrences within the first five years of follow-up were analyzed using Kaplan-Meier, Cox proportional hazard, and multivariate analysis to assess an association between TLE3 expression and response to therapy. TLE3 was expressed in approximately 30% of tumors and expression was associated with a favorable outcome only in patients who had received taxane as part of their treatment regimen (n = 173, HR = 0.62, P = 0.012; P(interaction) = 0.024). Further analysis revealed that the predictive association between TLE3 expression and outcome was strongest in patients with nonserous histology. High TLE3 expression predicts a favorable response to taxane containing chemotherapy regimens in ovarian carcinoma. Our findings warrant an independent evaluation of TLE3 as a potential therapeutic response marker for taxane-based chemotherapy in ovarian cancer.
Highlights
Transducin-like enhancer of split 3 (TLE3) is a transcriptional repressor that interacts with a chromatin complex acting downstream of adenomatous polyposis coli (APC) and b-catenin in the Wnt pathway [1]
Patient characteristics and tissue microarray (TMA) staining for transducin-like enhancer of split 3 (TLE3) expression
In the University of Alabama at Birmingham (UAB) cohort, 129 of 135 (96.7%) patients were treated with a regimen containing a taxane and a platinum class agent whereas in the Royal Hospital for Women (RHW) cohort 64 of 161 (39.8%) patients were treated with a regimen containing a taxane while the remainder were untreated, treated with a platinum class agent alone or unspecified (Table 1)
Summary
Transducin-like enhancer of split 3 (TLE3) is a transcriptional repressor that interacts with a chromatin complex acting downstream of adenomatous polyposis coli (APC) and b-catenin in the Wnt pathway [1]. TLE3 was one of several biomarkers found to be prognostic in all patients; the association with outcome was present only in patients who received treatment with either a taxane or a methotrexate containing regimen. The hypothesis that TLE3 expression was associated with response to taxane therapy was subsequently tested by conducting a retrospective validation study in a triple negative (estrogen receptor, progesterone receptor, and ERBB2 negative), uniformly high-grade breast cancer cohort. We have previously shown that transducin-like enhancer of split 3 (TLE3) is associated with outcome in patients with taxane-treated breast cancer and not in patients treated with anthracycline-based regimens without a taxane. The purpose of this study was to assess the association between TLE3 expression and recurrence in patients with ovarian carcinoma treated with a taxane containing regimen as opposed to those treated with a platinum-based agent alone
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