Methylation Of DAPK, P16/INK4a, P14 And HMLH1 Genes In Gallbladder Carcinoma

Objective: To investigate methylation of DAPK, P16/INK4a, P14 and hMLH1 genes in gallbladder carcinoma (GBC). Methods: Methylation-specific PCR was adopted to investigate methylation of DAPK, P16/INK4a, P14 and hMLH1 Genes in 33 cases of GBC tumor and corresponding non-tumor gallbladder tissues, 31 cases of chronic cholecystitis (CC) tissues. The relationship between methylation of DAPK, P16/INK4a, P14 and hMLH1 Genes and clinical data was analyzed. Results: In 33 cases of GBC tumor and corresponding non-tumor gallbladder tissues, the frequency of DAPK methylation was 51.51%, 19.35% respectively; the frequency of P16/INK4a methylation was 69.70%, 19.35% respectively; the frequency of P14 methylation was 48.48%, 22.58% respectively; the frequency of hMLH1 methylation was 30.30%, 16.12% respectively; Methylation of the four genes was more frequent in GBC than in non-tumor gallbladder tissues(P=0.001, P=0.000, P=0.002, P=0.003). At least one gene was methylated in 69.70% of GBC and 45.16% of non-tumor gallbladder tissue. One gene was methylated in 1 of GBC(3.03%). Two genes were methylated in 9 of GBC(27.27%). Three genes were methylated in 5 of GBC(15.15%),and four genes were methylated in 8 of GBC(24.24%). 17 of CC ( 54.84% ) in corresponding non-tumor gallbladder tissues were detected methylation in DAPK, P16/INK4a, P14 and hMLH1 Genes. All of genes were methylated in only l of non-tumor gallbladder tissues ( 3.23%) . Methylation frequency of the four genes in GBC was more than in non-tumor gallbladder tissues (P<0.05). In all of the methylated genes, DAPK, P16/INK4a and P14, both the diameter of the tumor and the distance of the encroached liver were longer than those of non-methylated, but no difference between ages of patients and types of histopathology, for GBC tissues. The methylation frequency of squamous-celled carcinoma / adenosquamous carcinoma were more than adenocarcinoma, for hMLH1 gene. Conclusion: Methylation of DAPK, P16/INK4a, P14 and hMLH1 genes probably correlated with GBC at its occurrence and developement of GBC; P16/INK4a methylation in GBC expressed higher frequency. Methylation of DAPK and hMLH1 genes probably expressed difference in racial regions in GBC.