Trophoblast Cell Surface Antigen 2 Expression in Human Tumors: A Tissue Microarray Study on 18,563 Tumors

Abstract

<b><i>Introduction:</i></b> Trophoblast cell surface antigen 2 (TROP2) is the target of sacituzumab govitecan, an antibody-drug conjugate approved for treatment of triple negative breast cancer and urothelial carcinoma. <b><i>Methods:</i></b> A tissue microarray containing 18,563 samples from 150 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by TROP2 immunohistochemistry. <b><i>Results:</i></b> TROP2 positivity was found in 109 tumor categories, including squamous cell carcinomas of various origins, urothelial, breast, prostate, pancreatic, and ovarian cancers (&#x3e;95% positive). High TROP2 expression was linked to advanced stage (<i>p</i> = 0.0069) and nodal metastasis (<i>p</i> &#x3c; 0.0001) in colorectal cancer as well as to nodal metastasis in gastric adenocarcinoma (<i>p</i> = 0.0246) and papillary thyroid cancer (<i>p</i> = 0.0013). Low TROP2 expression was linked to advanced stage in urothelial carcinoma (<i>p</i> &#x3c; 0.0001), high pT (<i>p</i> = 0.0024), and high grade (<i>p</i> &#x3c; 0.0001) in breast cancer, as well as with high Fuhrmann grade (<i>p</i> &#x3c; 0.0001) and pT stage (<i>p</i> = 0.0009) in papillary renal cell carcinomas. <b><i>Conclusion:</i></b> TROP2 is expressed in many epithelial neoplasms. TROP2 deregulation can be associated with cancer progression in a tumor-type dependent manner. Since anti-TROP2 cancer drugs have demonstrated efficiency, they may be applicable to a broad range of tumor entities in the future.