Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity and breast cancer?

Abstract

Women with breast cancer (BC) and antithyroid peroxidase (TPO) autoantibodies (TPOAb) have a better prognosis than women lacking TPOAb. Sera from women with TPOAb displayed immunoreactivity to BC tissue by immunofluorescence that was not apparent in women without TPOAb. We hypothesize a BC/thyroid shared antigen that provides a target for humoral or cellmediated immune activity; candidates include the sodium/iodide symporter (expressed in thyroid and BC), cross-reacting epitopes in TPO and lactoperoxidase (LPO) or TPO itself. As the association is with TPOAb, we investigated TPO expression in BC, breast peritumoral tissue (PT), other tissues (tumoral and not) and thyroid as positive control. Transcripts for known and novel TPO isoforms were detected in BC (n 5 8) and PT (n 5 8) but at approximately 10 4 -fold lower than in thyroid while in non-BC tumors (n 5 5) they were at the limit of detection. TPO was expressed also in adipose tissue (n 5 17), 10 3 -fold lower than in thyroid. Full length TPO (Mr 105-110 kDa) was detected in Western blots in the majority of examined tissues; preabsorption of the TPO antibody with recombinant TPO (but not LPO) reduced the signal, indicating specificity. The same occurred with some lower molecular weight bands, which could correspond to smaller TPO transcript isoforms, present in all samples. In conclusion, TPO is weakly expressed in BC and other tissues; this could partly explain the high frequency and protective role of TPOAb in BC patients. Further studies will investigate tissue specificity, function and immunogenicity of the novel TPO variants (some BC-specific) identified.

Is there an association between thyroid function abnormalities and breast cancer?

“…TPO-Abs are not thyroid-specific enzymes, and they can also be expressed in other tissues (24). In particular, TPO mRNA and protein have been found to be weakly but clearly expressed in BC tissues, peri-tumor tissues and in fat depots, and although they lack their functional activity, they maintain their antigenic role and can trigger B lymphocytes (37). Clinically, TPO-Abs have been associated with both an increased risk of BC (8,9,38) and a lower risk of BC; in some cases, TPO-Abs have even been associated with a lower frequency of distant metastases (39), a better outcome and better overall survival (27,38).…”

Thyroid autoimmunity as a window to autoimmunity: An explanation for sex differences in the prevalence of thyroid autoimmunity

“…A connection among TPO, TPO antibody, and breast cancer prognosis has been proposed (Muller et al, 2014). A mathematical description of the clinical progression of Hashimoto‫׳‬s thyroiditis can be found in Pandiyan et al (2013).…”

TPOAb and Thyroid Function Are Not Associated with Breast Cancer Outcome: Evidence from a Large-Scale Study Using Data from the Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001)

“…Furthermore, differences in the alternative splicing of TPO in the breast as compared to the thyroid have been described [25]; therefore, this might also result in different TPO epitopes being targeted.…”

“…Furthermore, TPO is expressed in BC tissue [25], providing a possible mechanistic link: a thyroid/breast, shared, autoimmune response might target tumour cells and improve BC outcome. If TPOAb+ was confirmed as associated with a better BC outcome, new BC therapeutic approaches based on antigen-specific immunotherapies targeting TPO could be explored.…”