p63 Expression Defines a Lethal Subset of Muscle-Invasive Bladder Cancers

作者：Choi Woonyoung^*; Shah Jay B; Mai Tran; Svatek Robert; Marquis Lauren; Lee I Ling; Yu Dasom; Adam Liana; Wen Sijin; Shen Yu; Dinney Colin; McConkey David J; Siefker Radtke Arlene

来源：PLos One, 2012, 7(1): 453-462.

DOI：10.1371/journal.pone.0030206

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. %26lt;br%26gt;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%26lt;0.0001). However, OS was shorter in patients with muscle-invasive tumors that retained p63 (p = 0.007). %26lt;br%26gt;Conclusions/Significance:Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the %26quot;epithelial%26quot; marker p63 in muscle-invasive tumors is associated with a worse outcome.

• 出版日期2012-1-10