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F17. Prognostic implication of aberrant promoter hypermethylation of CpG islands in adenocarcinoma of the lung
Young T Kim, Hee J Kang, Jeen Lee, Sun J Park, Seung H Lee, Curi Ann; SeoulGyenggi-do, Republic of Korea
Objective: DNA hypermethylation in promoter regions has been studied for various types of cancer. However, there is no clear evidence that shows methylation status can predict long-term survival in lung cancer.
Methods: We collected tissue from 72 cases of lung adenocarcinoma. The cancer and normal lung tissue were tested for DNA hypermethylation using methylation-specific PCR (MSP). The genes tested were p16INK4a, RARβP2, DAPK and MGMT, and GSTP. The status of the analyzed DNA methylation focused on long-term outcome as well as clinical variables, including cancer stage.
Results: DNA hyper-methylations were observed in 83%(60/72) for p16INK4a, 63%(45/72) for RARβP2, 32%(23/72) for DAPK, 17%(12/72) for MGMT, and 46%(33/72) for GSTP from the cancer tissue. From normal lung tissue, methylation was positive in 75%(54/72) for p16INK4a, 24%(17/72) for RARβP2, 10%(7/72) for DAPK, 6%(4/72) for MGMT, and 33%(24/72) for GSTP. During the mean follow-up period of 18±11(1-40) months, 25 patients(35%) developed recurrence and 13 died. Hypomethylation of DAPK in cancer tissue(p=0.04) and hypermethylation of RARβP2 in normal tissue(p=0.01) were significant variables that affected long-term survival. In multivariate analysis, male gender(p=0.04), hypomethylation of DAPK from cancer tissue(p=0.03), and hypermethylation of RARβP2 from normal tissue(p=0.01) were risk factors for poor survival. Pathologic stage(p=0.01) and hypomethylation of DAPK(p=0.07) from normal tissue were risk factors for recurrence.
Conclusions: DNA methylation status of CpG island seems to be a useful predictor of long-term outcome for adenocarcinoma of the lung. Further studies, including multiple genes, are necessary to increase its usefulness in the clinical setting.
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