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

Pathobiology. 2022;89(4):245-258. doi: 10.1159/000522206. Epub 2022 Apr 27.

Abstract

Introduction: 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.

Methods: 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.

Results: TROP2 positivity was found in 109 tumor categories, including squamous cell carcinomas of various origins, urothelial, breast, prostate, pancreatic, and ovarian cancers (>95% positive). High TROP2 expression was linked to advanced stage (p = 0.0069) and nodal metastasis (p < 0.0001) in colorectal cancer as well as to nodal metastasis in gastric adenocarcinoma (p = 0.0246) and papillary thyroid cancer (p = 0.0013). Low TROP2 expression was linked to advanced stage in urothelial carcinoma (p < 0.0001), high pT (p = 0.0024), and high grade (p < 0.0001) in breast cancer, as well as with high Fuhrmann grade (p < 0.0001) and pT stage (p = 0.0009) in papillary renal cell carcinomas.

Conclusion: 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.

Keywords: Breast cancer; Epithelial neoplasm; Immunohistochemistry; Neoplastic tissue; Tissue microarray; Trophoblast cell surface antigen 2; Urothelial carcinomas.

MeSH terms

  • Adenocarcinoma* / pathology
  • Antigens, Neoplasm
  • Carcinoma, Transitional Cell*
  • Cell Adhesion Molecules / metabolism
  • Female
  • Humans
  • Male
  • Trophoblasts / metabolism
  • Trophoblasts / pathology
  • Urinary Bladder Neoplasms*

Substances

  • Antigens, Neoplasm
  • Cell Adhesion Molecules