title: Immunohistochemical staining characteristics of nephrogenic adenoma using the PIN-4 cocktail (p63, AMACR, and CK903) and GATA-3.
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.
authors.affiliation: Departments of *Pathology ‡Internal Medicine §Urology †Michigan Center for Translational Pathology ∥Comprehensive Cancer Center ¶Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI #Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: McDaniel
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: Jesse K
authors.initials: JK
authors.lastname: McKenney
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis*; D000236:Adenoma / Q000175:diagnosis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D050990:GATA3 Transcription Factor / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D019998:Racemases and Epimerases / Q000032:analysis; D014571:Urologic Neoplasms / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C081876:CKAP4 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D008565:Membrane Proteins; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase