OTU-010 Vitamin D receptor as a marker of prognosis in oesophageal adenocarcinoma: a prospective cohort study

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Abstract

Background

Vitamin D receptor (VDR) expression has been associated with survival in several cancers. This study aims to evaluate the association between VDR expression and prognosis in oesophageal adenocarcinoma patients.

Methods

The study included 130 oesophageal adenocarcinoma patients who underwent neo-adjuvant chemotherapy and surgery at the Northern Ireland Cancer Centre between 2004 and 2012. Formalin fixed paraffin embedded (FFPE) resection specimens and matched clinical data were retrieved via the Northern Ireland Biobank. Tissue microarrays (TMAs) were created and VDR immunohistochemical analysis performed on triplicate 1 mm tumour cores from each block. Immunohistochemical VDR expression was assessed by two independent observers, blinded to the clinical data, by multiplying the staining intensity with the percentage of tumour cells staining positive for VDR, to give an H-score between 1 and 300. Comparison between maximum VDR expression and prognosis was calculated using Cox proportional hazards regression models adjusted for age, gender, nodal status, circumferential resection margin, lymphovascular invasion, smoking status and tumour location. Outcomes studied included overall survival, disease specific survival and recurrence free survival.

Results

During a mean of 3 (range 0.5–9) 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 0.26–0.94) and disease-specific survival (HR 0.50 95% CI 0.26–0.96), when comparing the highest with the lowest tertile of expression. These associations were strongest in sensitivity analysis restricted to junctional tumours.

Conclusions

This study is the first to demonstrate that patients with higher VDR expression in oesophageal adenocarcinoma have a more favourable prognosis. This study identifies VDR expression as a potential prognostic indicator although further work is needed to validate VDR as a prognostic marker and define its role in the aetiology and progression of oesophageal adenocarcinoma.

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