Trop2 Expression in Extramammary Paget's Disease and Normal Skin

Int J Mol Sci. 2021 Jul 19;22(14):7706. doi: 10.3390/ijms22147706.


Extramammary Paget's disease (EMPD) is a rare skin cancer arising in the apocrine gland-rich areas. Most EMPD tumors are dormant, but metastatic lesions are associated with poor outcomes owing to the lack of effective systemic therapies. Trophoblast cell surface antigen 2 (Trop2), a surface glycoprotein, has drawn attention as a potential therapeutic target for solid tumors. Sacituzumab govitecan, an antibody-drug conjugate of Trop2, has recently entered clinical use for the treatment of various solid cancers. However, little is known about the role of Trop2 in EMPD. In this study, we immunohistochemically examined Trop2 expression in 116 EMPD tissue samples and 10 normal skin tissues. In normal skin, Trop2 was expressed in the epidermal keratinocytes, inner root sheaths, and infundibulum/isthmus epithelium of hair follicles, eccrine/apocrine glands, and sebaceous glands. Most EMPD tissues exhibited homogeneous and strong Trop2 expression, and high Trop2 expression was significantly associated with worse disease-free survival (p = 0.0343). These results suggest the potential use of Trop2-targeted therapy for EMPD and improve our understanding of the skin-related adverse effects of current Trop2-targeted therapies such as sacituzumab govitecan.

Keywords: extramammary Paget’s disease; sacituzumab govitecan; targeted therapy; trophoblast cell surface antigen 2 (Trop2).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Apocrine Glands / metabolism
  • Biomarkers, Tumor
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation / genetics
  • Hair Follicle / metabolism
  • Humans
  • Immunoconjugates / pharmacology
  • Keratinocytes / metabolism
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Paget Disease, Extramammary / drug therapy
  • Paget Disease, Extramammary / genetics
  • Paget Disease, Extramammary / metabolism*
  • Paget Disease, Extramammary / pathology
  • Sebaceous Glands / metabolism
  • Skin / metabolism
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology


  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • Immunoconjugates
  • Membrane Glycoproteins
  • TACSTD2 protein, human
  • sacituzumab govitecan
  • Camptothecin