Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival

Methylation of 5 ' CpG islands in promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor su ppressor genes. The purpose of this study was to determine whether hypermet hylation of the adenomatous polyposis coli (APC) gene promoter occurs in pr imary non-small cell lung cancer (NSCLC), and whether hypermethylated APC h as any relationship with survival. APC promoter 1A methylation was determin ed in normal and corresponding tumor tissue from 91 NSCLC patients and in a control group of 10 patients without cancer, using a quantitative fluoroge nic real-time PCR (Taqman((R))) system. APC promoter methylation was detect able in 86 (95%) of 91 tumor samples, but also in 80 (88%) of 91 normal sam ples of NSCLC patients, and in only two (20%) of 10 normal lung tissues of the control group. The median level of APC promoter methylation was 4.75 in tumor compared to 1.57 in normal lung tissue (P < 0.001), Patients with lo w methylation status showed significantly longer survival than did patients with high methylation status (P = 0.041), In a multivariate analysis of pr ognostic factors, APC methylation was a significant independent prognostic factor (P = 0.044), as were pT (P = 0.050) and pN (P < 0.001) classificatio ns. This investigation shows that APC gene promoter methylation occurs in t he majority of primary NSCLCs, High APC promoter methylation is significant ly associated with inferior survival, showing promise as a biomarker of bio logically aggressive disease in NSCLC.