[1094] Comparison of p40 to p63 Expression in Micropapillary Urothelial Carcinoma (MPUC) and Conventional Urothelial Carcinoma (UC)

Bing Zhu, Xiaoqi Lin, Stephen M Rohan, Celina Villa, Elizabeth Gersbach, Yi Wang, Ximing Yang. Northwestern University, Chicago, IL

Background: MPUC is an aggressive variant of UC. p63 , a tumor suppressor gene, encodes two major isoforms (TA and ΔN) that differ in the structure of N-terminal domains. The widely used anti-p63 antibody, 4A4, recognizes both isoforms. The anti-p40 antibody recognizes ΔNp63 isoform only. Recently, decrease in p63 expression (4A4 labeling) has been described in high grade and high stage UC. Expression of p40 in UC has not been well studied.
Design: Immunohistochemistry (IHC) for p63 and p40 was performed on paraffin embedded tissue sections of 62 high grade UCs (HGUC), 16 low grade UCs (LGUC) (14 Tis and 2 T1) and 20 MPUCs (4Results: p63 and p40 expression were identified in non-neoplastic surface urothelium.

Table 1. IHC for p63 and p40 in UC.
MarkerPositivityMPUC (n=20)HGUC ≥T2 (n=46)HGUC LGUC (n=16)P Value
P63Positive cases (%)0.073.993.7100.0P1 < 0.001
 Positive Tumor Cells (%)0.030 ± 30.855 ± 24.589.4 ± 3.1P1 < 0.001, P2 < 0.001, P3 < 0.001
P40Positive cases (%)10.093.5100100.0P1 < 0.001
 Positive Tumor Cells (%)0.5 ± 1.660.0 ± 29.460.6 ± 23.692.8 ± 5.5P1 < 0.001, P2 < 0.001, P3 < 0.001
Student t test and Chi-Square test. P1: MPUC vs. HGUC or LGUC. P2: HGUC ≥ T2 vs. LGUC. P3: HGUC< T2 vs. LGUC.

Table 2. IHC for p63 and p40 in MPUC, LGUC or HGUC component of all cases studied and in tumors of different stages.
MarkerPositivityMPUC (n=20)HGUC (n=69)LGUC (n=42)≥T2 (n=62)P values
p63Positive Tumor Cells (%)0.0 ± 0.037.1 ± 30.986.1 ± 6.064.2 ± 32.622.3 ± 29.6P1 < 0.001, P2 < 0.001, P3 < 0.001, P4 < 0.001
p40Positive Tumor Cells (%)0.5 ± 1.551.4 ± 28.289.8 ± 5.868.3 ± 32.638.5 ± 33.6P1 < 0.001, P2 < 0.001, P3 < 0.001, P4 < 0.001
Student T test. P1: MPUC vs. HGUC; P2: MPUC vs. LGUC; P3: HGUC vs. LGUC; P4:

Conclusions: p63 expression is seen diffusely in all LGUCs, significantly decreased in HGUC and lost in MPUC. p40 expression is also decreased in HGUC and markedly decreased in MPUC. Based on these results, loss of p63 expression in a UC appears to be associated with adverse features—namely high grade, high stage, or MPUC. p40 is more frequently expressed in urothelial carcinoma irrespective of tumor grade, stage, or MPUC when compared to p63 and thus, may be a superior diagnostic marker than 4A4(p63). Further study including more cases and other UC variants are needed to substantiate these findings.
Category: Genitourinary (including renal tumors)

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 196, Tuesday Afternoon


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