TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma

Simple Summary Anaplastic thyroid carcinoma is a highly aggressive thyroid tumor with a poor prognosis. There are limited choices for the effective treatment of this type of carcinoma. Whether the targets of antibody-drug conjugates are expressed in anaplastic thyroid carcinoma remains unclear. Therefore, we examined expression rates of the following antibody-drug conjugate targets using the tissue microarrays of anaplastic thyroid carcinomas: human epidermal growth factor receptor 2, nectin-4, trophoblast cell surface antigen 2, glycoprotein non-metastatic B, and B7-H3. We found that glycoprotein non-metastatic B and B7-H3 were expressed in most anaplastic thyroid carcinoma tissues. Trophoblast cell surface antigen 2 and nectin-4 were expressed in 65% and 59% of anaplastic thyroid carcinoma tissues, respectively. Trophoblast cell surface antigen 2 was high expressed in anaplastic thyroid carcinoma undifferentiated from papillary thyroid carcinoma. In contrast, nectin-4 expression was high in patients with de novo anaplastic thyroid carcinoma. These cell membrane proteins are potential therapeutic targets for anaplastic thyroid carcinoma. Background: Anaplastic thyroid carcinoma (ATC) is a highly aggressive thyroid tumor with a poor prognosis. However, there are limited choices for ATC treatment. Recently, the effectiveness of antibody-drug conjugates has been demonstrated in various carcinomas. Whether the targets of antibody-drug conjugates are expressed in anaplastic thyroid carcinoma remains unclear. Methods: Fifty-four patients with ATC were enrolled in this study. Tissue microarrays were constructed using the archives of formalin-fixed paraffin-embedded tissue blocks. All sections were stained with the following antibody-drug conjugate targets: human epidermal growth factor receptor 2 (HER2), nectin-4, trophoblast cell surface antigen 2 (TROP-2), glycoprotein non-metastatic B (GPNMB), and B7-H3. Results: HER2 was negative in all tissues, whereas GPNMB and B7-H3 were expressed in most ATC tissues. TROP-2 and nectin-4 were expressed in 65% and 59% of ATC tissues, respectively. TROP-2 was expressed at significantly higher levels in ATC undifferentiated from papillary thyroid carcinoma than in ATC undifferentiated from follicular thyroid carcinoma and de novo ATC. In contrast, nectin-4 expression was markedly higher in patients with de novo ATC than in those with papillary and follicular thyroid carcinoma. Conclusions: TROP-2 and nectin-4 are potential therapeutic targets for ATC undifferentiated from papillary thyroid carcinoma and de novo ATC, respectively. GPNMB and B7-H3 potential for treating all types of ATC.