Expression of Novel Renal Tubular Associated Markers in Nephrogenic Adenoma (NA) of the Urothelial Tract: Potential Utility in Distinction from Its Malignant Mimics
Sambit K Mohanty, Nalan Nese, Mitual Amin, Manju Aron, Rugvedita Parakh, Ruta Gupta, Ping Zhang, Daniel Luthringer, Mahul B Amin. Cedars-Sinai Medical Center, Los Angeles, CA; Beaumont Medical Center, Royal Oak, MI
Background: NA of the bladder, urethra and renal pelvis is believed to represent renal tubular satellites/outposts in response to injury or metaplastic response to urothelial injury. Lesions have a range of histologic patterns, form a mass lesion, may have an infiltrative growth and morphologically mimic malignant lesions such as clear cell carcinoma of the bladder (CCC), urothelial carcinoma with glandular differentiation or nested pattern (UCa) and prostatic adenocarcinoma (PCa). This study aims at analyzing the utility of novel renal tubule-associated markers in differentiating NA from its malignant mimics.
Design: hKIM-1, Pax2, Pax8, racemase and S100A1 are renal tubule associated markers. The entire renal tubular system including the Bowman's capsule expresses Pax2, Pax8 and S100A1. hKIM-1 is expressed in injured proximal renal tubules and racemase is expressed primarily in proximal convoluted tubules. We analyzed the utility of a panel of immunohistochemical (IHC) markers [renal-associated markers - hKIM-1, Pax2, Pax8, racemase, S100A1; urothelial-associated marker S100p and MIB-1 (Ki67)] in the distinction of NA (n=39) from its histologic mimics: CCC (n=4), UCa (n=6) and PCa (n=14). The staining results were recorded in a semiquantitative fashion (0: negative, 1+: 1-25, 2+: 26-50, 3+: 51-100% and intensity as weak, moderate and strong). A MIB-1 (Ki-67) proliferation index (% positive in 100 cells counted) was ascertained for each case.
Results: IHC results are summarized in the table expressed as percentage positive.
13% of NA negative or weak for Pax2, Pax8 and racemase were strongly positive for hKIM-1. The range of MIB-1 proliferation index for NA, CCC, PCa, UCa was 1-4%, 20-50%, 5-30% and 10-40%, respectively.
|CCC||0||25||0||50||50 (weak)||100 (usually 1+)||25|