Promoter methylation profile in gallbladder cancer |
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Authors: | Juan Carlos Roa Leonardo Anabalón Iván Roa Angélica Melo Juan Carlos Araya Oscar Tapia Xavier de Aretxabala Sergio Muñoz Barbara Schneider |
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Institution: | (1) Department of Pathology, Faculty of Medicine, Universidad de La Frontera, Manuel Montt 112, Temuco, 478-1176, Chile;(2) Department of Pathology, Clínica Alemana de Temuco, Temuco, Chile;(3) Department of Surgery, Clínica Alemana de Santiago, Santiago, Chile;(4) Public Health Department, Universidad de La Frontera, Temuco, Chile;(5) Department of Pathology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA |
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Abstract: | Background 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.
Methods 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.
Results 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.
Conclusions 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. |
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Keywords: | CDKN2A MLH1 APC CDH1 FHIT immunohistochemical expression methylation gallbladder cancer |
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