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. ABSTRACT: 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.