Evaluation of ΔNp63 Expression in Urothelial Cell Carcinoma
Kamille A West, Darren J Buonocore, David Lucido, Lawrence Kiss, Beverly Wang, Violette Ghali. Beth Israel Medical Center, New York, NY
Background: Depth of invasion of urothelial cell carcinomas (UCCs) is an important prognostic factor. UCCs are known to express p63 by immunohistochemistry (IHC). Some biologic studies have implicated the ΔNp63 isoform (known for its use in non-small cell lung cancer) in conferring invasive potential in UCC; however, the data is limited and results are conflicting. There is a paucity of literature regarding immunolabeling of ΔNp63 (using the p40 antibody) in UCC. We sought to investigate IHC expression of ΔNp63 in UCC in order to further elucidate its effects on tumor behavior.
Design: We searched our archives for UCCs diagnosed between January-September 2012. Fifty (50) high-grade (30 invasive and 20 non-invasive) and 10 low-grade UCCs were selected. Cases that were poorly preserved or indeterminate for invasion were excluded. IHC was performed on all cases using the p63 antibody (4A4+Y4A3), and the p40 antibody (ΔNp63). IHC expression was semiquantitatively scored based on the percentage of tumor cells positive as follows: 90-100% (3+), 50-89% (2+), 10-49% (1+), <10% (0). A Χ2 test was used to determine the statistical significance of loss of p40 staining compared to p63 in high-grade non-invasive and invasive UCCs.
Results: p40 staining was uniformly less intense than p63 in normal and lesional tissue. Normal urothelium displayed constitutional (3+) expression of both markers with sparing of the umbrella cells. All of the low-grade UCCs exhibited diffuse (3+) expression of both markers. The results of IHC staining of the high-grade UCCs are listed in Table 1. All cases showed some degree of staining for p63. p40 staining was completely absent in four cases. In 78% of high-grade UCCs, the expression of p40 mimicked that of p63, while in 22% p40 was expressed in fewer cells. The results of the X2 test showed no significant difference between the stains for non-invasive high-grade UCCs (p= 0.1448); however, in high-grade invasive tumors, loss of p40 as compared to p63 was highly statistically significant (p=0.0092).
|IHC Ab||Score||High grade UCC, Invasive (n=30)||High grade UCC, Non-invasive (n=20)||Total High grade UCC (n=50)|
|p63||3||24 (80%)||16 (80%)||40 (80%)|
|2||4 (13.3%)||3 (15%)||7 (14%)|
|1||2 (6.7%)||1 (5%)||3 (6%)|
|0||0 (0%)||0 (0%)||0 (0%)|
|p40||3||18 (60%)||14 (70%)||32 (64%)|
|2||6 (20%)||4 (20%)||10 (20%)|
|1||3 (10%)||1 (5%)||4 (8%)|
|0||3 (10%)||1 (5%)||4 (8%)|