Cytoplasmic PPARγ is a marker of poor prognosis in patients with Cox-1 negative primary breast cancers
Résumé
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: 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.
Conclusion: 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.
Domaines
Sciences du Vivant [q-bio]
Origine : Fichiers éditeurs autorisés sur une archive ouverte
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