Aberrant methylation of H‐cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma

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Abstract
BACKGROUND Abnormalities in the H‐cadherin gene have been reported in several human malignancies, including nonsmall cell lung carcinoma (NSCLC). Aberrant methylation of the H‐cadherin promoter also has been reported in NSCLC, but its clinical significance remains to be elucidated. METHODS The authors studied H‐cadherin methylation in 305 patients with NSCLC to gain a further understanding of the clinicopathologic and prognostic significance of H‐cadherin methylation in patients with NSCLC. The methylation status of the H‐cadherin gene was investigated by using methylation‐specific polymerase chain reaction analysis in paraffin blocks from 305 patients with NSCLC. Ki‐67 expression was assessed by immunohistochemical staining. All statistical analyses were 2‐sided with a 5% Type I error rate. RESULTS H‐cadherin methylation was observed in 130 of 305 tumor samples (43%). The prevalence of H‐cadherin methylation was associated significantly with pathologic stage and was observed in 44% of patients with Stage I disease, in 23% of patients with Stage II disease, in 59% of patients with Stage III, and in 88% of patients with Stage IV disease (P = 0.001). H‐cadherin methylation occurred with a 2.71 times greater prevalence (95% confidence interval [95% CI], 1.21–6.09; P = 0.01) T2 tumors than in T1 tumors and with a 3.78‐fold greater prevalence (95% CI, 1.05–13.59; P = 0.04) in T3 tumors than in T1 tumors. However, lymph node metastasis was related inversely with H‐cadherin methylation (odds ratio = 0.51; 95% CI, 0.28–0.95; P = 0.03), and H‐cadherin methylation was not associated with the Ki‐67 labeling index (P = 0.53) or with tumor size (P = 0.89). No relation was found between H‐cadherin methylation and survival in patients with Stage I NSCLC (P = 0.51) or in patients with Stage II NSCLC (P = 0.46). CONCLUSIONS The current findings suggested an association between H‐cadherin methylation and tumor progression in NSCLC but had no prognostic significance in patients with early‐stage NSCLC. In addition, H‐cadherin methylation may be a valuable candidate molecular marker for the early detection of NSCLC. Cancer 2005. © 2005 American Cancer Society.