Autoimmune responses to thyroid/breast shared antigens to develop novel and specific therapies and diagnostics

An association between breast cancer (BC) and thyroid autoimmunity (TA) has been frequently observed and several small-scale studies correlated the presence of thyroid peroxidase (TPO) autoantibodies (TPOAb) with an improved BC outcome. The presence of an immune response to shared thyroid/breast antigens has been hypothesized: both tissues express the sodium iodide symporter (NIS) and have a peroxidase activity: TPO in thyroid and lactoperoxidase (LPO) in breast. I have identified 3 possibilities: i) BC patients with TPOAb may also have autoantibodies to NIS (NISAb) ii) BC may express TPO iii) TPOAb may cross-react with LPO in BC. This thesis aimed to identify the TA/BC shared antigen(s) and also investigated the prognostic role of TPOAb in a large cohort of BC patients. The presence of NISAb was investigated by flow cytometry using CHO cells stably transfected with human NIS. No positive response was obtained in 42 patients with BC and/or TA, therefore NIS is unlikely to be an antigen. TPO transcripts (RT-PCR, QPCR, LongRange PCR) and protein (western blot, immunohistochemistry, immunofluorescence) were detected in BC tissues but at levels 104 times less than in thyroid tissue. TPO was also expressed in adipose tissue and different cancers. Some potentially BC specific TPO isoforms were identified. The observational large-scale study conducted on 1974 women affected with BC did not reveal any evidence for a significant impact of TPOAb and/or thyroid function on BC prognosis. In conclusion, BC and thyroid tissues share similar properties and could be common targets of TA, with TPO being the most likely common antigen; further studies are needed to clarify the role of tissue-specific TPO isoforms. The roles of TPOAb and thyroid function on BC prognosis have to be reconsidered, maybe focusing on different TA aspects (e.g. goitre, different autoantibodies).