Journal of Gastroenterology

, Volume 41, Issue 3, pp 269–275 | Cite as

Promoter methylation profile in gallbladder cancer

  • Juan Carlos Roa
  • Leonardo Anabalón
  • Iván Roa
  • Angélica Melo
  • Juan Carlos Araya
  • Oscar Tapia
  • Xavier de Aretxabala
  • Sergio Muñoz
  • Barbara Schneider



Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time.


Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained.


All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied.


The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.

Key words

CDKN2A MLH1 APC CDH1 FHIT immunohistochemical expression methylation gallbladder cancer 


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Copyright information

© Springer-Verlag Tokyo 2006

Authors and Affiliations

  • Juan Carlos Roa
    • 1
  • Leonardo Anabalón
    • 1
  • Iván Roa
    • 1
    • 2
  • Angélica Melo
    • 1
  • Juan Carlos Araya
    • 1
  • Oscar Tapia
    • 1
  • Xavier de Aretxabala
    • 3
  • Sergio Muñoz
    • 4
  • Barbara Schneider
    • 5
  1. 1.Department of Pathology, Faculty of MedicineUniversidad de La FronteraTemucoChile
  2. 2.Department of PathologyClínica Alemana de TemucoTemucoChile
  3. 3.Department of SurgeryClínica Alemana de SantiagoSantiagoChile
  4. 4.Public Health DepartmentUniversidad de La FronteraTemucoChile
  5. 5.Department of PathologyLouisiana State University Health Sciences CenterNew OrleansUSA

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