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

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.