TGFβ1 and Not TGFβ2 Is Upregulated in Hashimoto Thyroiditis-Related Papillary Thyroid Carcinoma
Mark Petten, Matthew Brace, Martin Bullock, Jun Wang, Mark Taylor, Jonathan Trites, Robert Hart. Dalhousie University, Halifax, NS, Canada
Background: TGFβ is a cytokine with 3 isoforms. It is known to function as both a tumor suppressor and tumor promoter, yet there is limited information about what factors are involved in the functional switch and when this switch occurs. Recent discoveries in immunology indicate that TGFβ is one of the key cytokines required for the differentiation of Type 17 T helper cells (TH17), which have a dominant role in mediating chronic inflammation. Interleukin 17 (IL-17), the signature cytokine of TH17 cells, has been shown to be present in the tumor microenvironment of various cancers. Depending on the cancer in question, IL-17 may be either protective or non-protective. Recent data also suggests that patients with Hashimoto thyroiditis (HT) have an increase in both pro-inflammatory cytokines and TH17 lymphocytes in the serum and thyroid tissue. As HT may be a risk factor for papillary thyroid cancer (PTC), the aim of this study was to evaluate the expression levels of key molecules related to the TH17 cells, including TGFβ, in patients with HT and PTC.
Design: Fresh snap frozen tissue samples from 47 patients (n=12 PTC with HT, n=12 PTC without HT, n=11 benign thyroid tissue with HT and n=12 benign thyroid tissue without HT) were processed and RNA extracted to generate cDNA. Quantitative PCR (qPCR) was used to determine expression levels for IL-17, IL-17F, Il-6, IL-22, RORC, TGFβ-1, TGFβ-2, IL-1β, Foxp3 and IL-23p19.
Results: In the PTC with HT group there was significant increase in the expression of TGFβ1 and Foxp3 versus the other samples (p<0.05). Additionally, TGFβ1 was significantly increased in the PTC samples as a whole and IL-23p19 was found to be significantly increased in the HT group.
Conclusions: Upregulation of TGFβ, particularly TGFβ1, may play an important role in the development of PTC in patients with HT, possibly by promoting differentiation of TH17 cells, with downstream immunomodulatory effects. The relationship between TGFβ upregulation and BRAF V600E mutation in these patients is currently unknown and is a direction of future studies.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 48, Wednesday Afternoon