p53/PCDH17/Beclin-1 Proteins as Prognostic Predictors for Urinary Bladder Cancer

Abstract

Purpose: To determine whether p53, PCDH17, Beclin-1 expression is associated with clinicopathological characteristics of bladder cancer. Materials and Methods: 75 patients with non-muscle-invasive and muscle-invasive bladder cancer were included. Immunohistochemical staining for p53, PCDH17 and Beclin-1 were carried out on the same paraffin-embedded blocks serial sections of these patients who underwent surgery between 2010 and 2015. In addition, p53 gene mutations in these tumors were screened by DNA sequencing. Results: Forty-nine (66.7%) of 75 tumors had p53 gene mutations detected by DNA sequencing method. Of these tumors, 43 (86.0%) exhibited p53 high expression. Furthermore, p53 mutation and low expression of PCDH17 were significantly associated with muscle-invasive bladder cancer. Beclin-1 was also strongly associated with T stage. The p53 mutation, the expression of p53 and PCDH17 were significantly associated with survival from bladder cancer. In addition, patients with p53 high-expression or p53 mutation, PCDH17 low-expression and Beclin-1 low-expression significantly had a poor prognosis. Conclusions: Use of a DNA sequencing method to detect p53 gene mutations was consistent with an immunohistochemical method to detect p53 alterations. In conjunction with levels of p53/PCDH17/Beclin-1, p53 and PCDH17 were independently associated with prognosis; Beclin-1 only had a tendency towards overall survival. p53/PCDH17/Beclin-1 phenotype seems to play a more important role than p53 expression in bladder cancer outcome. It is also identified that p53/PCDH17, p53/Beclin-1 or PCDH17/Beclin-1 all have a cooperative and synergistic effect, which may provide us the potential biomarker for bladder cancer patients.

Keywords: Beclin-1; Urinary bladder neoplasms; p53; protocadherin 17.

Figure 1

Representative immunohistochemical staining for p53, PCDH17 and Beclin-1 in urinary bladder cancer, which is expressed in the nuclear or cytoplasm (200 ×). Case 1: p53 mutation/ p53 wild-type (A, D); Case 2: PCDH17 mutation/ PCDH17 wild-type (B, E); Case 3: Beclin-1 mutation/ Beclin-1 wild-type (C, F).

Figure 2

Kaplan-Meier survival curves of 60 Bladder Cancer patients who underwent surgical treatment according to p53 mutation and p53, PCDH17, Beclin-1 expression. (A) The overall survival rate for patients with p53 low-expression was significantly higher than that for patients with p53 high-expression (p=0.038). (B) The overall survival rate for patients with p53 mutation was significantly higher than that for patients with p53 wide-type (p=0.031). (C) The overall survival rate for patients with PCDH17 high-expression was significantly higher than that for patients with PCDH17 low-expression (p=0.031). (D) No significant difference between the overall survival rate for patients with Beclin-1 high-expression and that for patients with Beclin-1 low-expression (p=0.112).

Figure 3

Kaplan-Meier survival curves of 60 Bladder Cancer patients who underwent surgical treatment according to combined p53, PCDH17 and Beclin-1 expression, which was classified it into two types. (A) The overall survival rate for patients with p53 mutation plus PCDH17 expression (p=0.004). (B) The overall survival rate for patients with p53 mutation plus Beclin-1 expression (p=0.017). (C) The overall survival rate for patients with PCDH17 expression plus Beclin-1 expression (p=0.010). (D) The overall survival rate for patients with combined p53 and PCDH17 expression (p=0.002). (E) The overall survival rate for patients with combined p53 and Beclin-1 expression (p=0.008). (F) The overall survival rate for patients with combined p53 mutation and PCDH17 plus Beclin-1 expression (p=0.003). (G) The overall survival rate for patients with combined p53 expression and PCDH17 plus Beclin-1 expression (p=0.001).