A low nuclear-to-cytoplasmic ratio of VDR expression is an independent prognostic marker in breast cancer.

Abstract

The aim of this retrospective study was to analyze the prognostic value of cytoplasmic versus nuclear expression of the vitamin D receptor (VDR) in breast cancer (BC) tissue samples and to relate the results to clinicopathological parameters. VDR expression was assessed in 319 primary breast cancer patients using the Remmele and Stegner immunoreactive scoring (IRS) system. Follow-up data were obtained from the Munich Cancer Registry. The correlation with overall survival (OS) and disease-free survival (DFS) was calculated using univariate and multivariate analyses. Correlation analysis revealed a correlation between nuclear VDR expression and improved outcomes for both OS (p=0.004) and DFS (p=0.001). Conversely, cytoplasmic VDR expression was significantly associated with a shorter OS (p=0.003) and DFS (p<0.001). Additionally, both cytoplasmic and nuclear VDR expression were found to be independent markers of DFS (p<0.001; p=0.021) when examined alongside clinicopathological parameters. Moreover, nuclear VDR expression was positively associated with lower lymph node invasion (pN; p=0.01). For triple-negative patients, cytoplasmic VDR expression was found to have a significant inverse correlation with DFS (p<0.001). Lastly, the ratio of VDR nuclear/cytoplasmic was identified as an auxiliary independent marker of DFS and OS. These findings strongly indicate that the subcellular localization of VDR is crucial in determining BC prognosis. The expression of nuclear VDR appears to have a protective effect, while cytoplasmic VDR is associated with a more aggressive disease course. The data may help identify subgroups of patients with high-risk BC, possibly leading to specific options for targeted tumor therapy.