Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

Simple Summary Considering the immense development of today's therapeutic approaches in oncology towards customized therapy, this study aimed to assess the prognostic value of nuclear versus cytoplasmic retinoid X receptor alpha (RXR alpha) expression in breast cancer. Our results demonstrate that RXR alpha expression may have different roles in tumorigenesis according to its subcellular localization. This study strengthens the need for further research on the behavior of RXR alpha, depending on its intracellular localization. The aim of this retrospective study was to assess the prognostic value of cytoplasmic versus nuclear RXR alpha expression in breast cancer (BC) tissue samples and to correlate the results with clinicopathological parameters. In 319 BC patients, the expression of RXR alpha was evaluated via immunohistochemistry. Prognosis-determining aspects were calculated through uni- and multivariate analyses. Correlation analysis revealed a trend association with nuclear RXR alpha expression regarding an improved overall survival (OS) (p = 0.078), whereas cytoplasmic RXR alpha expression was significantly correlated with a poor outcomes in terms of both OS (p = 0.038) and disease-free survival (DFS) (p = 0.037). Strengthening these results, cytoplasmic RXR alpha was found to be an independent marker for DFS (p = 0.023), when adjusted to clinicopathological parameters, whereas nuclear RXR alpha expression was positively associated with lower TNM-staging, i.e., pT (p = 0.01), pN (p = 0.029) and pM (p = 0.001). Additionally, cytoplasmic RXR alpha expression was positively associated with a higher histopathological tumor grading (p = 0.02). Cytoplasmic RXR alpha was also found to be a negative prognosticator for Her-2neu-negative and triple-negative patients. Altogether, these findings support the hypothesis that the subcellular localization of RXR alpha plays an important role in carcinogenesis and the prognosis of BC. The expression of cytoplasmic RXR alpha is correlated with a more aggressive course of the disease, whereas nuclear RXR alpha expression appears to be a protective factor. These data may help to identify high-risk BC subgroups in order to find possible specific options in targeted tumor therapy.

Automated summary

This study assessed the prognostic value of nuclear versus cytoplasmic RXR alpha expression in breast cancer, showing that the subcellular localization of RXR alpha may have different impacts on tumorigenesis and prognosis. Cytoplasmic RXR alpha expression was associated with a more aggressive disease course, while nuclear RXR alpha expression appeared to be a protective factor, indicating potential implications for targeted tumor therapy.