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

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

David Dum  1 , Noushin Taherpour  1 , Anne Menz  1 , Doris Höflmayer  1 , Cosima Völkel  1 , Andrea Hinsch  1 , Natalia Gorbokon  1 , Maximilian Lennartz  1 , Claudia Hube-Magg  1 , Christoph Fraune  1 , Christian Bernreuther  1 , Patrick Lebok  1 , Till S Clauditz  1 , Frank Jacobsen  1 , Guido Sauter  1 , Ria Uhlig  1 , Waldemar Wilczak  1 , Stefan Steurer  1 , Sarah Minner  1 , Andreas H Marx  1   2 , Ronald Simon  1 , Eike Burandt  1 , Till Krech  1   3 , Andreas M Luebke  1
Affiliations

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

David Dum et al. Pathobiology. 2022.

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Pathobiology. 2023;90(1):69-70. doi: 10.1159/000526108. Epub 2022 Jul 28. Pathobiology. 2023. PMID: 37497985 Free PMC article. No abstract available.

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.

PubMed Disclaimer

Conflict of interest statement

The TROP2 antibody clone MSVA-733R was provided from MS Validated Antibodies GmbH (owned by a family member of GS).

Figures

Fig. 1
Fig. 1
TROP2 immunostaining of normal tissues. The panels show a strong TROP2 positivity of surface epithelial cells of the tonsil (a), urothelium of the urinary bladder (b), and the endometrium (c) as well as in acinar and basal cells of the prostate (d). TROP2 staining is somewhat weaker and largely limited to the most apical elements of the surface epithelium in the stomach antrum (e), distal tubuli and the visceral layer of the Bowman capsule of the kidney (f), and intrahepatic bile ducts of the liver (g). TROP2 immunostaining is lacking in colon epithelial cells (h).
Fig. 2
Fig. 2
TROP2 immunostaining in cancer. The panels show a strong, membranous, and cytoplasmatic TROP2 immunostaining in a squamous cell carcinoma of the oral cavity (a), a recurrent adenocarcinoma (Gleason 5 + 5 = 10) of the prostate (b), a breast cancer of no special type (c), a gastric adenocarcinoma (d), a papillary carcinoma of the thyroid (e), and an adenocarcinoma of the lung (f). TROP2 staining is absent in an epithelioid pleural mesothelioma (g) and a colorectal adenocarcinoma (h).
Fig. 3
Fig. 3
Ranking order of TROP2 immunostaining in cancers. Both the frequency of positive cases (blue dots) and the frequency of strongly positive cases (orange dots) are shown.
See this image and copyright information in PMC

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