Cytoplasmic PPARγis a marker of poor prognosis in patients with Cox-1 negative primary breast cancers

Abstract

Background: The aim of this study was to investigate the expression of the nuclear receptor PPARγ, together with that of the cyclooxygenases Cox-1 and Cox-2, in breast cancer (BC) tissues and to correlate the data with several clinicobiological parameters including patient survival. Methods: In a well characterized cohort of 308 primary BC, PPARγ, Cox-1 and Cox-2 cytoplasmic and nuclear expression were evaluated by immunohistochemistry. Correlations with clinicopathological and aggressiveness features were analyzed, as well as survival using Kaplan-Meier analysis. Results: PPARγwas expressed in almost 58% of the samples with a predominant cytoplasmic location. Cox-1 and Cox-2 were exclusively cytoplasmic. Cytoplasmic PPARγwas inversely correlated with nuclear PPARγand ER expression, but positively with Cox-1, Cox-2, and other high-risk markers of BC, e.g. HER2, CD133, and N-cadherin. Overall survival analysis demonstrated that cytoplasmic PPARγhad a strong correlation with poor survival in the whole cohort, and even stronger in the subgroup of patients with no Cox-1 expression where cytoplasmic PPARγexpression appeared as an independent marker of poor prognosis. In support of this cross-talk between PPARγand Cox-1, we found that Cox-1 became a marker of good prognosis only when cytoplasmic PPARγwas expressed at high levels. Conclusion: Altogether, these data suggest that the relative expression of cytoplasmic PPARγand Cox-1 may play an important role in oncogenesis and could be defined as a potential prognosis marker to identify specific high risk BC subgroups.