Immunohistochemical staining characteristics of nephrogenic adenoma using the PIN-4 cocktail (p63, AMACR, and CK903) and GATA-3

Am J Surg Pathol. 2014 Dec;38(12):1664-71. doi: 10.1097/PAS.0000000000000267.

Abstract

Nephrogenic adenoma (NA) is a benign lesion of the urinary tract associated with injury to the urothelium. The varied morphologic patterns of NA make it a potential diagnostic pitfall, because it can mimic closely prostatic adenocarcinoma and urothelial carcinoma. In current practice, an antibody cocktail comprising p63, CK903, and AMACR (PIN-4 cocktail) is frequently utilized to evaluate foci suspicious for prostatic adenocarcinoma. Although the staining characteristics of the individual components of the PIN-4 cocktail have been reported for NA, no study has described the expression patterns for NA when the stains are applied as a cocktail. GATA-3 is an emerging marker of urothelial carcinoma; however, the GATA-3 staining characteristics of NA have yet to be described. Sixty-three NA specimens (M:F=36:27, average age=51.4 y) from various locations in the urinary tract including urinary bladder (n=40), ureter (n=3), and urethra (n=20) were collected from the archives of 2 institutions. Immunohistochemical analysis with the PIN-4 cocktail and GATA-3 antibodies was performed, and the distribution and intensity of staining was recorded for each antibody in each case. PIN-4 cocktail staining revealed AMACR expression in 56% of cases, CK903 expression in 97%, and rare p63 positivity (in only 2 cases). Only 2 NA cases displayed an overall PIN-4 staining pattern compatible with prostate cancer. GATA-3 expression was noted in 40% of NAs. No correlation between AMACR, CK903, or GATA-3 positivity and histologic pattern or anatomic location was identified. Although heterogenous staining patterns were seen within individual cases, use of the PIN-4 cocktail effectively discriminates NA from prostate cancer because of the high frequency of coexpression of AMACR and CK903 within NA. In addition, GATA-3 is not a useful marker in differentiating between NA and urothelial carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenoma / diagnosis*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Child
  • Diagnosis, Differential
  • Female
  • GATA3 Transcription Factor / analysis
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / analysis
  • Middle Aged
  • Racemases and Epimerases / analysis
  • Urologic Neoplasms / diagnosis*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CKAP4 protein, human
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Membrane Proteins
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase