SUMMARY

Papillary thyroid carcinoma (PTC) incidence rates have steadily increased over the past few decades. PTC, unlike most malignancies, is unique among malignancies because the majority of staging systems identify age as a significant prognostic indication, and the incidence of PTC is higher in women than men. Besides its classical role in bone and calcium homeostasis, the active form of vitamin D with its receptor, vitamin D receptor (VDR),  has many non-classical effects; antiproliferative, prodifferentiating effects, and immunoregulation. Little is known about the expression of VDR protein in thyroid carcinoma. The aim of this study was to evaluate if there is a correlation between localizes VDR expression together with VDR (FokI/ rs2228570) gene polymorphisms and PTC, pathological characteristics, and papillary thyroid carcinoma aggressiveness among patients with PTC.

Pathological parameters of 153 patients analyzed and the cases were divided into four age groups (≤24 years, 25-44 years, 45-64 years, and ≥65 years). Then, the association of gender and age with histopathological features were evaluated. Then, out of 153 cases, 80 patients with histologically confirmed papillary thyroid carcinoma and 60 control individuals without PTC were enrolled in this study conducted at the Salahaddin University-College of science/ Department of Biology. We utilized immunohistochemistry to characterize VDR in PTC cells and adjacent non-cancerous tissue (NCTT). In addition, allele specific polymerase chain reaction (AS-PCR) was performed to assess the VDR gene polymorphism (FokI rs2228570) for blood of the controls and FFPE sections of the patients. 

Results showed that females were significantly more frequent in almost all age groups and are more susceptible for TC even when they are young. The four groups showed highly significant differences regarding extrathyroidal extension (ETE) which is more aggressive in older individuals’ tumor. In addition, old patients and males were significantly more likely to have larger tumor size. However, both gender and age non-significantly associated with multifocality and lymphovascular (LV) invasion.

VDR expression notably higher in the TC cells compared with that in NCTT. All TC samples were showed positive (IRS≥2). Moderate and strong staining intensity (55% and 30%, respectively) were observed in nearly most of the TC cells compare to adjacent NCTT which is mostly showed negative or weakly stained (28.75% and 56.25%, respectively). All multifocal tumors (100%) were strongly expressed VDR which is significantly different with unifocal tumors with P-value of 0.03. Statistical analysis for effect of FokI on PTC revealed a significant difference in allele frequency. T allele decreases the risk of PTC with OR 0.25 (P value < 0.0001). In addition, significantly decreased risk in CT patients (P value < 0.0001) OR =0.14 and in TT patients with P value=0.0014 (OR 0.05) were observed. Current study also showed no significant link between FokI genotype and the pathological characteristics of PTC.

Our results confirm that increasing age could really exert a negative prognostic effect, at least in terms of ETE risk and larger tumor size. In addition, females were more frequent in all age groups and significantly more likely than men to present at younger, while males represent larger tumor size. VDR expression could be used as a deferential marker to discriminate TC from normal thyroid tissue since the TC cells express more VDR than non-cancerous cells. However the VDR expression and the VDR polymorphism are poor prognostic markers for TC aggressive behaviors. VDR expression were higher in multifocality that may refer to antitumor response of VDR.