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

• Published in: Journal of translational medicine 2020-02, Vol.18 (1), p.94-94, Article 94
• Main Authors: Shao, Wanting, Kuhn, Christina, Mayr, Doris, Ditsch, Nina, Kailuwait, Magdalena, Wolf, Verena, Harbeck, Nadia, Mahner, Sven, Jeschke, Udo, Cavaillès, Vincent, Sixou, Sophie
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers; Biomarkers, Tumor; Breast cancer; Breast Neoplasms; Cancer therapies; Cell growth; Cox-1; Cox-2; Cyclooxygenase-1; Cytoplasm; Cytoplasmic; Humans; Immunoglobulins; Life Sciences; Ligands; Medical prognosis; Overall survival; Pathology; PPAR gamma; PPARγ; Prognosis; Receptor, ErbB-2; Statistical analysis; Tumors
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02271-6

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. 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. PPARγ was expressed in almost 58% of the samples with a predominant cytoplasmic location. Cox-1 and Cox-2 were exclusively cytoplasmic. Cytoplasmic PPARγ was inversely correlated with nuclear PPARγ and 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 PPARγ had 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 PPARγ expression appeared as an independent marker of poor prognosis. In support of this cross-talk between PPARγ and Cox-1, we found that Cox-1 became a marker of good prognosis only when cytoplasmic PPARγ was expressed at high levels. Altogether, these data suggest that the relative expression of cytoplasmic PPARγ and 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.