Abstract
Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. Bladder cancers detected at an early stage have a very high five-year survival rate, but when detected after local metastasis the rate is only about 50%. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of this study was to analyze UC cases reported in Athens, Ohio and investigate the major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines.Formalin fixed and paraffin embedded transurethral resection tissues were immunostained for Wnt5a, Ror-2, CTHRC1 and E-cadherin. In addition, in vitro studies using UC cell lines were investigated for Wnt5a/PCP signaling and epithelial mesenchymal transition (EMT) gene expression. The IHC results showed a correlation between the expression of Wnt5a, Ror2 and CTHRC1 with high histological grade of the tumor, while E-cadherin showed an opposite trend of expression. Real time RT-PCR results showed that RNA expression of the Wnt5a/ PCP pathway genes vary in low and high grade UC cell lines and that the high grade cell lines exhibited signs of EMT.These findings support that Wnt5a-Ror2 signaling plays a role in UC, support the potential use of Wnt5a as a prognostic marker and provide evidence that Wnt5a signaling may be used as an effective molecular target for novel therapeutic tools.
Highlights
Bladder cancer is the fourth most common cancer among men
A total of 75 cases where confirmed as urothelial carcinoma (UC) with 52 (69.3%), being high grade (HG) lesions and 23 (30.7%), being low grade (LG) lesions
In the group studied with the diagnosis of UC the likelihood for men and women to have HG versus LG tumors were 2.5 and 1.5 times, respectively (Figure 1B)
Summary
Bladder cancer is the fourth most common cancer among men. About 74,000 new cases are diagnosed, and result in 16,000 deaths each year in the United States [1]. Many bladder cancers at first diagnosis are found still confined to the superficial layer of the bladder wall, but 35% of the diagnoses have invaded into deeper layers including muscle. 95% of bladder cancers arise from the urothelium, causing urothelial carcinoma (UC) [2, 3]. Urothelial carcinoma is diagnosed and treated via transurethral resection (TUR). The World Health Organization (WHO) devised a 2 tier system in 2004, distinguishing low grade and high grade UC tumors. Low grade tumors maintain recognizable architecture with minimal changes in polarity, nuclear size, shape, and chromatin texture, while high grade tumors have disorganized architecture and frequent mitotic figures as well as increased pleomorphism and clumped chromatin [2]. The heterogeneous UC group includes tumors with different biological behaviors, and recurrence after the initial treatment is a common feature [3]
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