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

Cancers

Soji Toda¹  Ai Matsui¹  Hiroyuki Iwasaki¹  Daisuke Murayama¹  Nao Saito²  Kazumasa Sekihara²  Daisuke Hoshino²  Yoichiro Okubo³  Hiroyuki Hayashi⁴  Hirotaka Nakayama⁵  Nobuyasu Suganuma⁶  Yohei Miyagi⁷  Shinya Sato⁷ 

[1] Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama 241-8515, Japan;Department of Cancer Biology, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan;Department of Pathology, Kanagawa Cancer Center, Yokohama 241-8515, Japan;Department of Pathology, Yokohama Municipal Citizen’s Hospital, Yokohama 221-0855, Japan;Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka 254-8502, Japan;Department of Surgery, Yokohama City University, Yokohama 236-0004, Japan;Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan;

关键词: ADC;    ATC;    HER2;    TROP-2;    Nectin-4;    GPNMB;   

DOI  :  10.3390/cancers14030579

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown