title: Significance of PML and p53 protein as molecular prognostic markers of gallbladder carcinomas.
abstract: 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.
authors.affiliation: Research Institute and Hospital, National Cancer Center, Seoul, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Sun Whe
authors.initials: SW
authors.lastname: Kim
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000401:mortality* / Q000473:pathology; D005260:Female; D005706:Gallbladder Neoplasms / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D000071156:Promyelocytic Leukemia Protein; D015996:Survival Rate; D014157:Transcription Factors / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D025521:Tumor Suppressor Proteins / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070576:PML protein, human