PAX8 (+)/p63 (+) Immunostaining Pattern in Renal Medullary Carcinoma (RMC): An Intermediate Phenotype between Urothelial Carcinoma of Upper Urinary Tract (UUC) and Collecting Ducts Carcinoma (CDC)
R Albadine, L Schultz, A Billis, H Ellwood, DE Baydar, A Garvin, JI Epstein, P Argani, G Netto. Johns Hopkins University, Baltimore; UNICAMP State University, Campinas, Brazil; Hacettepe, Ankara, Turkey
Background: Renal Medullary carcinoma (RMC) is a rare highly aggressive tumor affecting young pts with sickle cell trait/disease. RMC displays variable morphology that may overlap with those of UUC and CDC. PAX8 is a lineage restricted transcription factor expressed in renal tubules. We here investigate the expression pattern of PAX8 in RMC and its utility, in combination with p63 in resolving the differential diagnosis of renal pelvis malignancies.
Design: Archival tissues from 12 RMC, 21 CDCs and 34 invasive UUC were retrieved from participating institutional files. Standard immunohistochemistry for PAX8 (Protein tech group, Inc. IL) and p63 (NeoMarkers) were performed on routine and TMA sections using an automated Bond-Laica stainer. Positive extent of staining was categorized as focal (<25%), multifocal (25-75%) or diffuse (>75%). Intensity of PAX8 and p63 nuclear staining was assigned an incremental 0 to 3+ score.
Results: PAX8: All 12 (100%) RMC and 21 (100%) CDC were positive for PAX8 (multifocal/diffuse;). PAX8 staining intensity was moderate to strong in 9/12 (75%) of RMC and 19/21 (90%) of CDC cases. In contrast, 31/34 (91%) UUC were negative for PAX8. p63: p63 was positive in 7/12 (58%) RMC and in 3/21 (14%) CDC. Staining was focal in 6/7 RMC and strong in 4/7. Almost all (97%) UUC were p63 positive (moderate/strong and multifocal/diffuse in 80% of cases). The one p63 negative UUC was a microinvasive high grade tumor and was also negative for PAX8.
Conclusions: We suggest a binary panel of PAX8 and p63 as an aid in the differential diagnosis of high grade renal sinus epithelial neoplasms. (PAX8+/p63+) profile supported the dx of RMC with a sensitivity of 58.3% and specificity of 89%. (PAX8+/p63-) profile supported the diagnosis of CDC with a sensitivity of 85.7% and a specificity of 89%. Finally (PAX8-/p63+) profile supported the diagnosis of UUC with a sensitivity of 88% and a specificity of 100%. The concomitant expression of p63 and PAX8 in RMC seen in our study further suggests an intermediate phenotype between renal tubular and a urothelial differentiation in RMC.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 144, Tuesday Morning