Vitamin D receptor is highly expressed in precancerous lesions and esophageal adenocarcinoma with significant sex difference

Zhou, Zhongren; Xia, Yinglin; Bandla, Santhoshi; Zakharov, Vladislav; Wu, Shaoping; Peters, Jeffery H; Godfrey, Tony E.; Sun, Jun

doi:10.1016/j.humpath.2014.02.029

Cited by 23 publications

(29 citation statements)

References 32 publications

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“…Zhou et al [ 47 ] observed diverse expression of VDR in esophageal adenocarcinomas and squamous cell cancers, with higher expression in the former. In the adenocarcinomas authors found no relationship between VDR expression and tumor stage, metastases and survival.…”

Section: Discussionmentioning

confidence: 99%

Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients

Jóźwicki

Brożyna

Siekiera³

et al. 2015

IJMS

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Vitamin D3 shows tumoristatic and anticancer effects by acting through the vitamin D receptor (VDR), while hydroxylation of 25-hydroxyvitamin D3 at position 1α by CYP27B1 is an essential step in its activation. The expression of both the VDR and CYP27B1 has been found in many normal and cancer tissues, but there is a lack of information about its expression in human bladder cancers. The aim of the present research was to examine whether the expression of the VDR and CYP27B1 in bladder cancer was related to the prognostic markers and disease outcome. We analyzed VDR and CYP27B1 in samples of tumor and normal tissues obtained from 71 urinary bladder cancer patients. The highest VDR immunostaining was found in normal epithelium and was significantly lower in bladder cancer cells (p < 0.001 with Mann–Whitney U test). VDR expression was lowest in more advanced (pT2b–pT4) (p = 0.005 with Mann–Whitney U test) and metastasizing cancers (p < 0.05 and p = 0.004 with Mann–Whitney U test for nuclear and cytoplasmic VDR immunostaining, respectively). The lack of cytoplasmic and nuclear VDR was also related to shorter overall survival (for cytoplasmic VDR immunolocalization 13.3 vs. 55.3 months of survival, HR = 1.92, p = 0.04 and for nuclear VDR immunostaining 13.5 vs. 55.3 months of survival, HR = 2.47, p = 0.002 with Mantel-Cox test). In cases with the lack of high cytoplasmic VDR staining the non-classic differentiations (NDs) was observed in higher percentage of tumor area. CYP27B1 expression was lower in cancer cells than in normal epithelial cells (p = 0.03 with Mann–Whitney U test), but its expression did not correlate with tumor stage (pT), metastasizing, grade, mitotic activity or overall survival. In conclusion, expression of the VDR and CYP27B1 are deregulated in urothelial bladder cancers. Although our results showing a relationship between the decreased VDR expression and prognostic markers and survival time indicate potential usefulness of VDR as a new indicator of a poorer prognosis, further studies are needed in different patient cohorts by independent groups to validate this hypothesis. We also suggest that vitamin D-based therapies may represent an adjuvant strategy in treatment for bladder cancers expressing VDR.

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Section: Discussionmentioning

confidence: 99%

Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients

Jóźwicki

Brożyna

Siekiera³

et al. 2015

IJMS

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“…These findings contrast with those from the only other published study to have considered the impact of VDR expression on oesophageal cancer survival. In a study of 116 patients in the USA, no significant difference in overall survival (21 months in high VDR expression versus 20 months in low VDR expression) was demonstrated between groups with high and low VDR expression ( p = 0.99) [ 14 ]. There are multiple differences in that study's design compared with ours that may account for the conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…To date, there has been little research investigating VDR expression and oesophageal adenocarcinoma outcomes. However, several published papers have reported differences in VDR expression when comparing native, pre-malignant and oesophageal adenocarcinoma tissue in cross-sectional analyses from different patients [ 14 , 15 ]. One study reported no VDR staining in normal oesophageal squamous mucosa, whereas Barrett's mucosa and low grade dysplasia had strongly positive VDR staining (95% and 100%, respectively), which then decreased slightly in tissue from patients with adenocarcinoma (79%) [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D receptor as a marker of prognosis in oesophageal adenocarcinoma: a prospective cohort study

McCain¹,

Trainor

McManus

et al. 2018

Oncotarget

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AimsVitamin D receptor (VDR) expression has been associated with survival in several cancer sites. This study aims to evaluate the association between VDR expression and prognosis in oesophageal adenocarcinoma patients.ResultsDuring a median of 2.5 (maximum 9) years of follow-up, 75 patients died. In analysis adjusted for confounders, higher VDR expression was associated with an improved overall survival (HR 0.49 95% CI 0.25–0.96) and disease-specific survival (HR 0.50 95% CI 0.26–0.99), when comparing the highest with the lowest tertile of expression. These associations were strongest in sensitivity analysis restricted to junctional tumours.ConclusionsThis study is the first to demonstrate that patients with higher VDR expression in oesophageal adenocarcinoma have a more favourable prognosis. Further work is needed to validate these findings, and to define the role of VDR in the aetiology, progression and management of oesophageal adenocarcinoma.MethodsOesophageal adenocarcinoma specimens and clinical data were collected from 130 patients treated with neo-adjuvant chemotherapy prior to surgical resection at the Northern Ireland Cancer Centre between 2004 and 2012. Tissue microarrays were created and immunohistochemical staining for VDR was performed on triplicate tumour cores from each resection specimen. Cox proportional hazards models were applied to evaluate associations between VDR, according to tertiles of expression, and survival outcomes.

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“…The VDR protein was considered to be highly expressed if 10% or more of the cells stained with an intensity score of 2+ or 3+, as described in 2014 by Zhou et al . 48 in esophageal adenocarcinoma and precancerous lesions.…”

Section: Methodsmentioning

confidence: 99%

Vitamin D and vitamin D receptor in patients with ophthalmic pterygium

et al. 2017

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Pterygium, an ultraviolet radiation (UV)-related disease, is a relatively benign process, but since it displays tumor-like features, it has been proposed to be a neoplastic-like growth disorder. Vitamin D performs a number of functions in addition to calcium homeostasis, as inhibition of cell proliferation, activation of apoptotic pathways, and inhibition of angiogenesis. Since the antitumor actions of vitamin D are mediated primarily through the nuclear vitamin D receptor (VDR), the aim of the present study was to investigate vitamin D status in patients with pterygium and in control subjects, and VDR immunohistochemical expression in samples of pterygium and normal conjunctiva in order to evaluate a possible role of vitamin D pathway in the pathogenesis of the disease. Serum vitamin D concentration was measured among 41 patients with pterygium and 47 volunteers by an automated chemiluminescence immunoassay. Moreover, 23 formalin-fixed and paraffin-embedded pterygium biopsy samples and 24 conjunctiva\ud specimens were treated for the immunohistochemical demonstration of VDR using the streptavidin-biotin alkaline phosphatase method. No differences were observed about vitamin D level between patients with pterygium and control group, but significant differences between VDR immunolocalization in pterygium and normal conjunctiva\ud were observed (P=0.00001). In conjunctiva, the immunoreactivity, localized mainly in cytoplasm of epithelial cells, may probably demonstrate VDR regulation of cell growth, differentiation, and apoptosis, while in pterygium VDR co-localization in the nucleus and cytoplasm of epithelial cells may indicate alternative nuclear pathways by which vitamin D might exert its antiinflammatory and anti-proliferative effects by the regulation of gene expression

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Vitamin D receptor is highly expressed in precancerous lesions and esophageal adenocarcinoma with significant sex difference

Cited by 23 publications

References 32 publications

Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients

Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients

Vitamin D receptor as a marker of prognosis in oesophageal adenocarcinoma: a prospective cohort study

Vitamin D and vitamin D receptor in patients with ophthalmic pterygium

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