Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: a study combining quantitative immunohistochemistry with digital slide image analysis

Publication date: Available online 25 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Petros Charalampoudis, Georgios Agrogiannis, Konstantinos Kontzoglou, Gregory Kouraklis, Georgios C. Sotiropoulos
BackgroundIn breast cancer, hormonal receptors hold promise for developingnovel targeted therapies. The thyroid exerts its actions via the thyroid hormone receptors alpha and beta. The clinical significance of the expression of thyroid hormone receptors in breast cancer is unclear.Material and MethodsWe studied thyroid hormone receptor alpha (TRa) expression in 82 samples from 41 women with ductal invasive breast cancer and no thyroid disease. We performed quantitative immunohistochemistry with digital image analysis and correlated TRa expression with clinicopathological parameters.ResultsTRa was expressed in both normal breast epithelium and breast cancer, but expression in breast cancer was significantly lower. TRa was expressed significantly less in larger and grade III tumors. Conversely, breast cancers with lymphovascular invasion showed increased TRa expression compared to cancers without lymphovascular invasion. TRa expression was not significantly different between node-positive and node-negative breast cancers, nor among different hormonal profiles and intrinsic subtypes.DiscussionThis is the first-in-human study to combine quantitative immunohistochemistry with image analysis to study TRa expression in women with ductal invasive breast cancer and no clinical or biochemical evidence of thyroid dysfunction. We confirm that TRa is expressed in both normal and malignant breast epithelium and suggest that TRa expression is downregulated during breast carcinogenesis. Larger and higher grade breast cancers demonstrate partial loss in TRa expression. Alterations in TRa expression take place even in the absence of clinical or biochemical thyroid disease. The underlying mechanism of these findings and their potential significance in survival and relapse mandate further research.



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