Subcellular localization of thyroid hormone receptor beta is associated with grade, FIGO stage and disease outcome in ovarian cancer

Zielsetzung Thyroid hormone receptor beta (THRβ) acts as ligand activated transcription factor and seems to function as a tumour suppressor in different types of cancer. Within this study we investigated whether THRβ is associated with clinico-pathological parameters or prognosis of ovarian cancer (OC) patients.

Methoden THRβ and its isoform THRβ1 were assessed in 156 OC samples using immunohistochemistry (IHC). IHC staining of cellular compartments was evaluated separately by a semi-quantitative immunoreactivity score, binarized and tested for association to clinical and pathological data including histological subtype, grading, staging (FIGO) and overall survival. Since THRβ/β1 may act as a heterodimer, a series of other steroid hormone receptors was screened for potential interaction with THRβ/β1.

Ergebnisse Nuclear localization of THRβ/β1 was most frequent in OC of serous histology (p (THRβ)=0.001; p (THRβ1)< 0.001). THRβ was translocated to the cytoplasmic compartment in high grade (p=0,025) and advanced stage (p=0,005) OC independent of histologic subtype. Cytoplasmic localization of neither THRβ nor THRβ1 was correlated to lymphonodular spread. Both THRβ (p< 0.001) as well as THRβ1 (p=0.023) were associated with impaired OS when shifted to the cancer cell cytoplasm. This also remained significant within multivariate testing. Finally, cytoplasmic THRβ was negatively correlated to presence of ER alpha (p=0.042).

Zusammenfassung Cytoplasmatic localization of THRβ and THRβ1 was associated with reduced OS in this study. Since THRβ/β1 mainly act via regulation of gene transcription, cytoplasmatic shifting might be interpreted as an escape mechanism of OC cells in order to stop THRβ/β1 from acting as a tumour suppressor.

Publication History

Article published online:
07 October 2020