BACKGROUND: p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationship between p63 expression and survival is not clear.
METHODOLOGY/PRINCIPAL FINDINGS: We used real-time PCR to characterize p63 expression and several genes implicated in epithelial-to-mesenchymal transition (EMT) in human bladder cancer cell lines (n = 15) and primary tumors (n = 101). We correlated tumor marker expression with stage, disease-specific (DSS), and overall survival (OS). Expression of E-cadherin and p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin. Non-muscle-invasive (Ta and T1) bladder cancers uniformly expressed high levels of E-cadherin and p63 and low levels of the mesenchymal markers. Interestingly, a subset of muscle-invasive (T2-T4) tumors maintained high levels of E-cadherin and p63 expression. As expected, there was a strongly significant correlation between EMT marker expression and muscle invasion (p<0.0001). however="" os="" was="" shorter="" in="" patients="" with="" muscle-invasive="" tumors="" that="" retained="" p63="" p="0.007).</p">
CONCLUSIONS/SIGNIFICANCE: Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the "epithelial" marker p63 in muscle-invasive tumors is associated with a worse outcome.
Written by:
Choi W, Shah JB, Tran M, Svatek R, Marquis L, Lee IL, Yu D, Adam L, Wen S, Shen Y, Dinney C, McConkey DJ, Siefker-Radtke A Are you the author?
Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America
Reference: PLoS One. 2012;7(1):e30206
doi: 10.1371/journal.pone.0030206
PubMed Abstract
PMID: 22253920