Nuclear vitamin D receptor expression is associated with improved survival in non-small cell lung cancer - PubMed (original) (raw)

Nuclear vitamin D receptor expression is associated with improved survival in non-small cell lung cancer

Malini Srinivasan et al. J Steroid Biochem Mol Biol. 2011 Jan.

Abstract

Vitamin D has been shown to have anti-proliferative effects in a wide variety of cancers including lung cancer. The anticancer effects of vitamin D are mediated primarily by its active metabolite, 1,25-dihydroxyvitamin D (calcitriol), through vitamin D receptor (VDR) signaling. However, thus far there have been no studies evaluating the association between VDR expression and survival outcome in lung cancer. Using immunohistochemical analysis, we evaluated VDR expression, separately in the nucleus and cytoplasm, in lung cancer samples from 73 non-small cell lung carcinoma (NSCLC) patients with no prior therapy, and investigated the association between VDR expression and overall survival (OS). Cox proportional hazard models were used for our primary analyses. There were 44 deaths during a median follow-up of 51 months (range 13-93 months). High nuclear VDR expression was associated with improved OS after adjusting for age, gender, stage, smoking status, and histology (adjusted hazard ratio, 0.36; 95% confidence interval, 0.17-0.79). There was no association between cytoplasmic VDR expression and OS. Our results suggest that nuclear VDR status may be a prognostic marker in NSCLC. Future large studies to replicate our findings and to assess the impact of VDR gene polymorphisms on VDR expression are required as therapies targeting the vitamin D signaling pathway may be influenced by VDR status in the target lung cancer tissue.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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Figures

Figure 1

Figure 1

VDR immunohistochemical expression across various histologies. A. Nuclear VDR expression, squamous cell carcinoma. B. Cytoplasmic VDR expression, adenocarcinoma. C. Nuclear and cytoplasmic VDR expression, adenocarcinoma. D. Cytoplasmic VDR expression, large cell carcinoma. (Original magnification. A, C: 400X; B, D: 200X). VDR: Vitamin D receptor

Figure 2

Figure 2

Kaplan-Meier survival curves for nuclear and cytoplasmic VDR expression. A. Nuclear VDR expression. Patients with high nuclear VDR expression had better probability of OS compared to those with low nuclear VDR expression (P=0.077, log-rank test). B. Cytoplasmic VDR expression. No difference in OS between patients with high versus low cytoplasmic VDR expression (P=0.963, log-rank test). VDR: Vitamin D receptor; OS: Overall survival

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