Decreased expression of the thyroid-stimulating hormone receptor in poorly-differentiated carcinoma of the thyroid

Poorly-differentiated carcinomas (PDCs) occupy an intermediate position between differentiated (follicular and papillary) and undifferentiated carcinomas (UDCs) based on morphology and behavior. However, its definition remains unclear, especially in the differentiation of thyroid function. To characterize the hormonal differentiation of PDCs, in addition to the morphological definition, we immunohistochemically investigated the thyroid-stimulating hormone receptor (TSHR) and thyroid transcription factor 1 (TTF-1) as regulators of thyroid hormonal function and differentiation. We comparatively studied their expression in 15 papillary carcinoma (PTC), 8 PDC and 8 UDC cases and further analyzed their correlation to proliferation activity as estimated by the MIB-1 index. All cases of PTC and PDC expressed the TSHR, whereas all cases of UDC did not. Notably, most of the PDCs showed more decreased and heterogeneous expression in the poorly-differentiated component than in the well-differentiated one within the same case. Examining the heterogeneous areas in PDC, we found an inverse relationship between TSHR expression and the MIB-1 index, that is, decreased TSHR expression was correlated to high proliferation. Unexpectedly, TTF-1 expression was observed in almost all of the PTC and PDC cases and in half of the UDC cases; therefore, it was not useful to distinguish PDC from PTC or UDC. In conclusion, we demonstrated that TSHR expression was decreased in PDCs despite conserved TTF-1 expression and that it correlated to the proliferative activity in PDCs.