Tumor Biology

, Volume 35, Issue 2, pp 1417–1426 | Cite as

BCL6 overexpression is associated with decreased p19ARF expression and confers an independent prognosticator in gallbladder carcinoma

  • Peir-In Liang
  • Chien-Feng Li
  • Li-Tzong Chen
  • Ding-Ping Sun
  • Tzu-Ju Chen
  • Chung-Hsi Hsing
  • Han-Ping Hsu
  • Ching-Yih Lin
Research Article


B cell lymphoma 6 (BCL6) is a protein that is vital for lymphogenesis. Its expression has been well established in lymphoma, especially in diffuse large B-cell lymphoma. Its role in carcinogenesis is less well understood. Previous study shows that BCL6 expression may regulate p19 functions, an important regulator for the p53 pathway. No prior study has attempted to evaluate the significance of BCL6 and p19ARF expression in a large cohort of patients with gallbladder carcinomas (GBCs). We selected 164 patients with GBC and performed immunostains for BCL6 and p19ARF. BCL6 expression and p19ARF expression were evaluated using a histochemical score (H-score). We then correlated the results with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS). BCL6 overexpression was significantly associated with high pT status, high TNM stage, higher histological grade (p = 0.029), vascular invasion, perineurial invasion, high Ki-67 labeling index, and low p19 expression. Importantly, BCL6 overexpression in GBC was strongly associated with worse DSS (p < 0.0001) and DFS (p < 0.0001) in the univariate analysis, and remained independently predictive of adverse outcomes (p = 0.001, hazard ratio (H.R.) = 3.098 for DSS; p = 0.002, H.R. = 2.255 for DFS). Low p19ARF expression was correlated with a poor DSS (p = 0.0144) and DFS (p = 0.0032) in the univariate analysis but was not prognosticatory in the multivariate analysis. In GBC, BCL6 overexpression correlated with adverse phenotypes and decreased p19ARF expression. BCL6 overexpression also independently predicts worse DSS and DFS, suggesting it has a role in tumorigenesis or carcinogenesis and could be a potential prognostic indicator in GBC.


Gallbladder carcinoma BCL6 p19ARF Prognosis 



This work was supported by grants (NSC101-2320-B-384-001-MY3) from the National Science Council, Taiwan, (100-TMP-009-3 and DOH101-TD-C-111-004) Department of Health, Taiwan, and (100CM-TMU-01) Chi Mei Medical Center, Tainan, Taiwan. The authors also appreciate the BioBank of Chi Mei medical Center to provide the tumor samples.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Peir-In Liang
    • 1
  • Chien-Feng Li
    • 2
    • 3
    • 4
    • 5
  • Li-Tzong Chen
    • 3
    • 6
  • Ding-Ping Sun
    • 7
  • Tzu-Ju Chen
    • 2
  • Chung-Hsi Hsing
    • 8
    • 9
  • Han-Ping Hsu
    • 10
  • Ching-Yih Lin
    • 11
    • 12
  1. 1.Department of Pathology, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiung 807Taiwan
  2. 2.Department of PathologyChi-Mei Foundation Medical CenterTainan City 710Taiwan
  3. 3.National Institute of Cancer ResearchNational Health Research InstitutesTainan City 704Taiwan
  4. 4.Graduate Institute of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiung 807Taiwan
  5. 5.Department of BiotechnologySouthern Taiwan University of Science and TechnologyTainan City 710Taiwan
  6. 6.Department of Internal Medicine, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiung 807Taiwan
  7. 7.Division of General Surgery, Department of SurgeryChi-Mei Medical CenterTainan City 710Taiwan
  8. 8.Department of AnesthesiologyChi-Mei Medical CenterTainan City 710Taiwan
  9. 9.College of MedicineTaipei Medical UniversityTaipei City 110Taiwan
  10. 10.College of MedicineChina Medical UniversityTaichung City 404Taiwan
  11. 11.Division of Gastroenterology and Hepatology, Department of Internal MedicineChi-Mei Foundation Medical CenterTainan City 710Taiwan
  12. 12.Department of Leisure, Recreation, and Tourism ManagementSouthern Taiwan University of Science and TechnologyTainan City 710Taiwan

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