Expression profiling of Thyroid-Hormone-Receptor alpha isoforms in breast cancer

Introduction: Both Thyroid-Hormone-Receptor alpha (TRα) 1 and 2 are processed from a gene named THRA by alternative splicing. While TRα1 holds oncogenic activity, TRα2 is suspected to act as a repressor of transcription thereby potentially antagonizing TRα1 signalling. Whether an immune-profiling of breast cancer (BC) taking into account both receptors may be of prognostic interest, remains to be unknown.

Materials: A cohort of 266 BC patients was studied.

Methods: TRα1 and TRα2 were detected in BC tissue (n = 266) by immunohistochemistry and correlated to clinico-pathological parameters.

Results: TRα1 and TRα2 were identified in a significant fraction (TRα1: 196/266; TRα2: 77/266) of BC samples. While TRα2 was positively correlated to hormone receptor staining, 82.4% of triple negative cases were found to express TRα1. Thus to further sub-classify the study sample the following immuno-phenotypes were defined: TRα1^pos/TRα2^neg (140/266; 52.6%), TRα1^neg/TRα2^pos (21/266; 7.9%), TRα1^pos/TRα2^pos (56/266; 21.1%), TRα1^neg/TRα2^neg (49/266; 18.4%). Interestingly, patients' TRα1/TRα2 profile was associated with PFS (p = 0.043). Women classified as TRα1^pos/TRα2^neg presented with significant shortened PFS (p = 0.017) as compared to those identified with TRα1^neg/TRα2^pos BC.

Conclusion: The data presented here further support our in vitro findings demonstrating that TRα1 may act as an oncogene in BC. As a high percentage of triple negative BC cases was identified to express TRα1, TRα1 may gain interest as an alternative anti-endocrine target in these patients.