Digital Image Analysis Shows Associations between Vitamin D Receptor, Age, and Tumor Type in Endometrial Carcinoma
Amy S Joehlin-Price, Julie A Stephens, David E Cohn, Adrian A Suarez. Ohio State University Wexner Medical Center, Columbus, OH
Background: The vitamin D receptor (VDR) influences many processes from calcium homeostasis to cellular proliferation and maturation. Ligand dependent and independent pathways have been described that involve nucleo-cytoplasmic translocations of VDR. Some of these may be at play in common malignancies such as colon and breast carcinomas. Additionally, recent research indicates an interplay between vitamin D, insulin resistance, and adiposity, the latter of which is an established risk factor for endometrial carcinoma (EC).
Design: Immunohistochemistry (IHC) with a commercially available VDR antibody (Santa Cruz Biotechnology) was performed on sections of a tissue microarray (TMA) of 381 EC. Digital slide images were produced with the Aperio ScanScope XT (Vista, CA). Tissue Studio 3.5 software by Definiens (Munich, Germany) was used to analyze component pixels, leading to quantification of the intensity and completeness of IHC stain in epithelial tissue only. A percentage for high intensity VDR staining was assigned to each core. Clinical data was extracted from electronic medical records and the high-intensity VDR staining was compared to age, tumor type, tumor stage, body mass index (BMI), and presence or absence of four IHC stains for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6).
Results: IHC displayed cytoplasmic EC staining almost exclusively. EC from women <50 years of age had a significantly higher VDR than those of patients ≥50 years of age (36.38% +/- 22.24 vs 26.97% +/-18.15), p=0.009, Wilcoxon Rank Sum Test. The Spearman's Correlation Coefficient between age and EC VDR was also significant at -0.115, p=0.024, showing a slight decrease in VDR as age increased. Additionally, FIGO grade 1 and 2 EC showed significantly higher VDR than higher grade tumors (29.29% +/- 18.68 vs 23.84% +/- 19.01), p=0.007. VDR did not correlate with BMI, stage, or MMR expression.
Conclusions: VDR localizes to the cytoplasm of neoplastic cells in EC where it may be polyubiquitinated and degraded. EC VDR expression is slightly but significantly higher in EC of younger women and in lower grade tumors. These findings indicate a possible role for VDR and its ligands and coregulators in EC. While these associations are unlikely to have immediate clinical, prognostic, or treatment implications for EC patients, further investigation is clearly warranted.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 126, Tuesday Morning