Aberrant methylation of E-cadherin and H-cadherin genes in nonsmall cell lung cancer and its relation to clinicopathologic features.
BACKGROUND
Lung cancer is the leading cause of cancer deaths worldwide. The epigenetic inactivation of certain genes by aberrant promoter methylation plays an important role in the pathogenesis of lung cancer. In addition, DNA hypermethylation is an extremely promising cancer marker. Cadherins are cell adhesion molecules that modulate the epithelial phenotype and regulate tumor invasion. Although the aberrant methylation of E-cadherin (CDH1) or H-cadherin (CDH13) genes has been reported in lung cancer, to the authors' knowledge, the relation between the concurrent hypermethylation in E-cadherin and H-cadherin has not been explored to date.


METHODS
The authors investigated the methylation status of the promoter region of human E-cadherin and H-cadherin genes in resected samples of primary nonsmall cell lung cancer (NSCLC) using methylation-specific polymerase chain reaction (MSP) analysis and correlated the results with clinicopathologic characteristics. The methylation status of the promoter regions of the E-cadherin and H-cadherin genes was examined by using nested MSP in 88 primary lung cancers and paired adjacent normal tissues. Data were compared with clinicopathologic features.


RESULTS
The frequency of methylation in neoplastic and corresponding nonneoplastic lung tissues was 30 of 88 tissue samples (34.1%) and 5 of 88 tissue samples (5.7%) for E-cadherin and 26 of 88 tissue samples (29.5%) and 7 of 88 tissue samples (8%) for H-cadherin, respectively. In addition, in 9 patients (10.2%), both genes were methylated. Although there was no significant difference in the overall survival of patients according to the methylation pattern of the E-cadherin gene alone or the H-cadherin gene alone, patients with NSCLC who had hypermethylation of both genes had a significantly longer overall survival. However, no correlation was observed between their methylation status and any other clinicopathologic factors.


CONCLUSIONS
The current findings suggested that simultaneous methylation of the E-cadherin and H-cadherin genes occurs in a subset of NSCLCs and may be used as a prognostic marker for patients with NSCLC. However, further studies with large numbers of patients will be needed to confirm the findings.
Kim
Dong Sun
DS
Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Kim
Mi Jin
MJ
Lee
Ji Yun
JY
Kim
Young Zoo
YZ
Kim
Eun Jin
EJ
Park
Jae Yong
JY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015820:Cadherins / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D015996:Survival Rate
D014408:Biomarkers, Tumor; D015820:Cadherins; C099972:H-cadherin