A Cautionary Note Regarding the Use of PAX-2 Immunohistochemistry (IHC) in Differentiating Metastatic Clear Cell Renal Cell Carcinoma (CC-RCC) from Adrenal Cortical Lesions (ACL): A Tissue Microarray Study of 245 Cases
JK McKenney, M Fujiwara, JP Higgins, N Gokden, AR Sangoi. Stanford, Stanford, CA; UAMS, Little Rock, AR
Background: PAX-2, a transcription factor expressed during renal development, is a useful marker for distinguishing metastatic CC-RCC from potential mimics. We recently noted PAX-2 nuclear reactivity in normal adrenal cortex suggesting a lack of specificity. In this study, we evaluate PAX-2 IHC in a large number of ACL and metastatic CC-RCC, including well-differentiated (WD) and poorly differentiated (PD) tumors.
Design: IHC analysis for PAX-2 was performed on 61 ACL (41 cortical adenomas, 4 cortical adenomas of uncertain malignant potential, 7 cortical carcinomas, 6 cortical hyperplasias, 3 cortical rests) and compared with 184 metastatic CC-RCC using tissue microarray technology. CC-RCCs were classified as WD when morphologic features strongly suggested CC-RCC or PD when RCC would not have been suspected by morphology. Staining intensity and extent were semiquantitatively scored (0-3+) on duplicate sections using two dilutions (1:50 and 1:100), and a mean intensity (MI) and mean extent (ME) were calculated.
Results: IHC sensitivities are in Table 1. Specificities for metastatic CC-RCC (overall) versus ACL by PAX-2 dilution are listed in Table 2. Results did not vary among the various ACL studied.
PAX-2 Reactivity by Titer
|PAX-2 (1:50)||PAX-2 (1:100)|
|ACL||35/61 (57%)||0/61 (0%)|
|MI=1.1; ME=1.5||MI=0; ME=0|
|CC-RCC (overall)||148/184 (80%)||111/184 (60%)|
|MI=2.5; ME=2.5||MI=2.4; ME=2.6|
|CC-RCC (WD)||115/133 (86%)||88/133 (66%)|
|MI=2.5; ME=2.7||MI=2.4; ME=2.8|
|CC-RCC (PD)||33/51 (65%)||23/51 (45%)|
|MI=2.4; ME=2.3||MI=2.4; ME=2.4|
Specificity for metastatic CC-RCC
|PAX-2 (1:50 dilution)||43%|
|PAX-2 (1:100 dilution)||100%|
Conclusions: ACL may show faint, usually 1+ nuclear PAX-2 expression (57%), which can be eliminated by antibody dilution. Since not all ACL have this expression, negative control tissues must be chosen carefully. Antibody dilution significantly decreased the sensitivity of PAX-2 for CC-RCC. The alternative, a requirement of 3+ staining intensity with more concentrated antibody, also lowered the sensitivity. PAX-2 did show immunoreactivity in the subset of PD tumors, but with decreased sensitivity (65 and 45%). This study highlights problems with the use of PAX-2 in the distinction of adrenal cortex from CC-RCC, and underscores the importance of using a panel of antibodies in this diagnostic setting.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 135, Tuesday Afternoon