Vitamin D receptor and progesterone receptor protein and gene expression in papillary thyroid carcinomas: associations with histological features.

Abstract

Vitamin D receptor (VDR) and progesterone receptor (PR) expression has been described in papillary thyroid carcinoma (PTC) but data regarding association with tumor histological characteristics and localization of the protein expression are scarce. Formalin-fixed, paraffin-embedded specimens from 45 patients with PTC (cases) were retrieved and tumor histological data were recorded. We analyzed gene and protein expression of VDR and PR and gene expression of vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzymes in follicular cancer cells and the adjacent non-neoplastic thyroid tissue (NNTT). VDR mRNA and protein expression was higher in PTC compared with NNTT (p<0.05). The protein was globally localized in the cytoplasm and cell membranes of the neoplastic cells in all cases, with differences in intensity. Cytoplasmic positivity was stronger in the majority of cases. Membranous positivity was also evident in cases, whereas in NNTT was generally weak and in a low percentage of the cells. Expression of CYP 24A1, but not CYP27B1, was increased in approximately all PTC specimens and was associated with lymph node metastasis and extrathyroidal extension. PR mRNA was increased in 34% and protein expression was present in 57% of cases, and none of NNTT. PR, but not VDR, mRNA expression was significantly associated with the tumor size (r=0.645, p=0.007). We provide evidence for the expression pattern of VDR, PR and CYP24A1 in the progression of PTC. Rapid anti-tumor responses of vitamin D in PTC may be blocked due to inactivation of local vitamin D metabolism.