Significance of PML and p53 protein as molecular prognostic markers of gallbladder carcinomas

Molecular markers for cancers are not only useful for cancer detection and prognostic prediction, but may also serve as potential therapeutic targets. In order to identify reliable molecular markers for prognostic prediction in gallbladder carcinoma (GBC), we evaluated the immunohistochemical expression of 15 proteins, namely p53, p27, p16, RB, Smad4, PTEN, FHIT, GSTP1, MGMT, E-cadherin, nm23, CD44, TIMP3, S100A4, and promyelocytic leukemia (PML) in 138 cases of GBC using the tissue microarray method. The prognostic significance was analyzed for each protein. Overexpression of p53 and S100A4, and loss of p27, p16, RB, Smad4, FHIT, E-cadherin and PML expression were associated with poor survival. In particular, PML and p53 showed considerable potential as independent prognostic markers. Patients with normal PML and p53 expression displayed favorable outcomes, compared to those showing abnormal expression of either or both proteins (49% vs. 23% in a 5-year survival rate; 60 months vs. 11 months in median survival, respectively; P=0.009). Thus, PML and p53 are potential candidates for development as clinically applicable molecular prognostic markers of GBC, and may be effective therapeutic targets for the disease in the future.