Polyclonal S100A1 Antibody Distinguishes Oncocytoma from Chromophobe RCC in Cytogenetically-Proven Renal Tumors and Fine Needle Aspirations
MS Hirsch, P Dal Cin, JF Krane, JL Hornick. Brigham & Women's Hospital, Boston, MA
Background: Recent reports have shown that a monoclonal antibody (Ab) to S100A1 distinguishes renal oncocytic neoplasms with relatively high sensitivity and specificity. However, the Ab used is no longer commercially available, and the reported cases were not correlated/confirmed with cytogenetics. The aims of this study were 1) to re-establish the sensitivity and specificity of a commercially available polyclonal S100A1 Ab in cytogenetically-proven renal epithelial tumors, and 2) to determine if S100A1 is useful in distinguishing oncocytic neoplasms evaluated by FNA.
Design: A polyclonal Ab to S100A1 was used to stain 1) 2 tissue microarrays (TMAs) containing 171 consecutive renal tumors with karyotypes (125 clear cell RCCs, 25 papillary RCCs, 10 chromophobe RCCs, and 11 oncocytomas); 2) sections of cytogenetically proven oncocytomas (12) and chromophobe RCCs (6) from nephrectomy specimens; and 3) 25 renal oncocytic neoplasms obtained by FNA. All cases were also stained for conventional S100B protein.
Results: In the TMAs, S100A1 was positive in 67% of clear cell RCCs, 60% of papillary RCCs, and 82% of oncocytomas; all chromophobe RCCs were negative. In the cytogenetically-proven nephrectomy tumors, all oncocytomas were positive for S100A1 and all chromophobe RCC were negative. In cell block (CB) preparations, it was necessary to confirm the presence of diagnostic tissue by H&E, as material was often scant and/or admixed with non-neoplastic renal tubules which are also positive for S100A1. Of the 25 CBs, S100A1 was positive in 18/19 (95%) oncocytomas (cytoplasmic pattern) and equivocal in 1 case; 4/6 chromophobe RCCs were negative for S100A1, 1 was positive (membranous pattern), and 1 was equivocal. All TMA, whole mount and FNA cases were negative for conventional S100B protein.
Conclusions: Consistent with prior reports, S100A1 demonstrates low overall specificity for oncocytoma, as clear cell and papillary RCC are also positive. However, when the differential diagnosis is oncocytoma vs chromophobe RCC, sensitivity and specificity are very high (100% in cytogenetically-proven cases). Focal staining in TMA and CB preparations decreases sensitivity and specificity (90% and 93%, respectively; combining TMA and CB specimens) due in part to sampling error; however, a granular cytoplasmic pattern favors oncocytoma. Positive staining of admixed renal tubular epithelium is a potential pitfall when interpreting S100A1 in CBs. Conventional S100B Ab cannot be used for this differential diagnosis.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 54, Wednesday Afternoon