J Breast Cancer.  2013 Mar;16(1):16-22.

The Role of the CDH1 Promoter Hypermethylation in the Axillary Lymph Node Metastasis and Prognosis

• Jung SP
• Kim S
• Nam SJ
• Kim I
• Bae JW

Abstract

PURPOSE
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).
CONCLUSION
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.

Keyword

Breast neoplasms; Lymph nodes; Methylation; Recurrence; Tumor suppressor genes

MeSH Terms

Breast Neoplasms
Disease-Free Survival
Genes, Tumor Suppressor
Humans
Lymph Nodes
Methylation
Neoplasm Metastasis
Polymerase Chain Reaction
Prognosis
Recurrence

Figure

• 

  Figure 1 Representative methylation-specific polymerase chain reaction results for the CDH1 genes. Note the unmethylated primary tumor and the metastatic axillary lymph node in patient 1 (hollow arrows). Solid arrows (patient 2) indicate the methylated primary tumor and the metastatic axillary lymph node. P=primary tumor; LN=axillary lymph node; M.W.=molecular weight (bp=base pair); P.C.=positive control; M=methylated tissue; U=unmethylated tissue.

• 

  Figure 2 Multivariate analysis curves for the relapse-free survival (RFS) according to the methylation status. (A) RFS according to the methylation status of the primary tumor (p=0.046). (B) RFS according to the methylation status of the metastatic axillary node (p=0.352). Primary=methylation status in primary tumor; LN=methylation status in axillary lymph node.

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