The utility of p63, p40, and GATA-binding protein 3 immunohistochemistry in diagnosing micropapillary urothelial carcinoma

Hum Pathol. 2014 Sep;45(9):1824-9. doi: 10.1016/j.humpath.2014.04.015. Epub 2014 May 8.


Micropapillary urothelial carcinoma (MPUC) is an uncommon variant of urothelial carcinoma (UC) with an aggressive clinical course. There have been limited studies on the UC markers GATA-binding protein 3 (GATA3), p63, and p40 in MPUC. Our study investigated the immunoreactivity of these 3 markers in MPUC compared with conventional UC of different grades and stages. Immunohistochemistry was performed on 62 cases of high-grade urothelial carcinoma (HGUC), 16 low-grade urothelial carcinoma (LGUC), and 20 MPUC. p63 expression was strong and diffuse in all LGUC, significantly decreased in high stage and HGUC, and virtually absent in MPUC. p40 expression was decreased in HGUC and markedly decreased in MPUC relative to LGUC. These results suggest that loss of p63 expression in a UC appears to be associated with adverse features--including cases with micropapillary differentiation. Decreased GATA3 expression was seen frequently in high-grade and high-pathologic stage (≥pT2) tumors but was retained in MPUC cases. The findings of retained GATA3 expression in MPUC, which often shows a loss of expression of other urothelial markers such as p63, may be helpful for determining the origin of micropapillary carcinoma of unknown primary. Compared with the traditional markers p63 and p40, GATA3 is the most sensitive marker of conventional UC and MPUC.

Keywords: GATA3; Micropapillary; Urothelial carcinoma; p40; p63.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Papillary / metabolism*
  • Carcinoma, Papillary / pathology
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / pathology
  • Cohort Studies
  • Female
  • GATA3 Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / metabolism
  • Urologic Neoplasms / metabolism*
  • Urologic Neoplasms / pathology
  • Urothelium / pathology


  • Biomarkers, Tumor
  • CKAP4 protein, human
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Membrane Proteins
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins