title: The role of the CDH1 promoter hypermethylation in the axillary lymph node metastasis and prognosis.
abstract: OBJECTIVE
  Hypermethylation of the tumor suppressor genes is frequently observed in the tumor development and progression. However, the correlation between the hypermethylation of the tumor suppressor genes, CDH1 and the axillary lymph node (ALN) metastasis is not fully elucidated. To verify the role of the CDH1 promoter hypermethylation in the ALN metastasis and prognosis, we compared the methylation status of the CDH1 genes in the primary lesion and the paired metastatic ALNs.
  
  
  METHODS
  We selected a total of 122 paraffin-embedded specimens of the primary and paired metastatic lymph node from 61 breast cancer patients and analyzed the frequency of hypermethylation in the primary and metastatic lymph node using the methylation-specific polymerase chain reaction. In addition, the methylation status of CDH1 was analyzed with the clinicopathologic characteristics, the disease-free survival and disease-specific survival.
  
  
  RESULTS
  The hypermethylation of CDH1 gene was identified in 54 (88.5%) of the 61 patients who had axillary metastasis. The hypermethylation status of the CDH1 gene was significantly increased in the metastatic ALNs compared with that in the primary tumors (60.7% vs. 45.9%, p<0.001). The hypermethylation status of the CDH1 genes in the metastatic ALNs was associated with a poor histologic grade (p=0.041) and the patients who had methylated tumor in the primary lesion showed worse disease-free survival than the patients who did not have methylated tumor (p=0.046).
  
  
  CONCLUSIONS
  This study suggests that hypermethylation of the CDH1 gene may play a pivotal role in the metastasis of the axillary lymph node and the breast cancer recurrence.
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Korea University Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Seung Pil
authors.initials: SP
authors.lastname: Jung
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.forename: Insun
authors.initials: I
authors.lastname: Kim
authors.forename: Jeoung Won
authors.initials: JW
authors.lastname: Bae
keywords: Breast neoplasms; Lymph nodes; Methylation; Recurrence; Tumor suppressor genes