Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

The aim of this study was to investigate the expression of thyroid hormone receptor beta 1 (THR beta 1) by immunohistochemistry in breast cancer (BC) tissues and to correlate the results with clinico-biological parameters. In a well-characterized cohort of 274 primary BC patients, THR beta 1 was widely expressed with a predominant nuclear location, although cytoplasmic staining was also frequently observed. Both nuclear and cytoplasmic THR beta 1 were correlated with high-risk BC markers such as human epidermal growth factor receptor 2 (HER2), Ki67 (also known as MKI67), prominin-1 (CD133), and N-cadherin. Overall survival analysis demonstrated that cytoplasmic THR beta 1 was correlated with favourable survival (p = 0.015), whereas nuclear THR beta 1 had a statistically significant correlation with poor outcome (p = 0.038). Interestingly, in our cohort, nuclear and cytoplasmic THR beta 1 appeared to be independent markers either for poor (p = 0.0004) or for good (p = 0.048) prognosis, respectively. Altogether, these data indicate that the subcellular expression of THR beta 1 may play an important role in oncogenesis. Moreover, the expression of nuclear THR beta 1 is a negative outcome marker, which may help to identify high-risk BC subgroups.