J Gynecol Oncol.  2008 Dec;19(4):241-245. 10.3802/jgo.2008.19.4.241.

Hypermethylation of E-cadherin in endometrial carcinoma

• Park JH
• Lee BI
• Song ES
• Whang SO
• Lee WY
• Cho SJ

• KMID: 2173413
• DOI: http://doi.org/10.3802/jgo.2008.19.4.241

Abstract

OBJECTIVE
Hypermethylation of CpG island is a common mechanism for the inactivation of tumor suppressor genes. Hypermethylation of the E-cadherin promoter region has been rarely studied in endometrial carcinoma of Korean women. The purpose of this study is to investigate methylation status of E-cadherin promoter region in endometrial carcinomas and endometrial hyperplasias, and analyze the correlation with clinicopathologic variables in endometrial carcinomas.
METHODS
We examined the methylation status of the E-cadherin promoter region using methylation specific polymerase chain reaction and immunohistochemical expression (IHC) of E-cadherin in 30 endometrioid endometrial carcinomas and 20 endometrial hyperplasias, and correlated these results with various clinicopathological factors of endometrial carcinomas.
RESULTS
Decreased expression of E-cadherin was detected in 13 of 30 (43.3%) endometrial carcinomas and in 1 of 20 (5%) endometrial hyperplasias (p=0.009). Promoter hypermethylation was detected in 12 of 30 (40%) endometrial carcinomas and 2 of 20 (10%) endometrial hyperplasias (p=0.015). Methylation status did not have a significant influence on the tumor grade and lymph node metastasis. However, the hypermethylation rate was significantly higher in stage above Ic (p=0.025). Decreased expression of E-cadherin was associated with tumor grade, tumor stage, and lymph node metastasis in endometrial carcinomas (p=0.01, p=0.02, p=0.03). There was no correlation between DNA hypermethylation and decreased expression of E-cadherin in endometrial carcinomas (p>0.05).
CONCLUSION
These results indicate that hypermethylation of E-cadherin promoter region is a frequent event in endometrial carcinoma, which may play an important role in the progression of carcinogenesis. Also, the promoter methylation of E-cadherin in endometrial carcinoma was found to be significantly associated with higher stage above Ic.

Keyword

E-cadherin; Hypermethylation; IHC; Endometrial carcinoma

MeSH Terms

Cadherins
CpG Islands
DNA
Endometrial Hyperplasia
Endometrial Neoplasms
Female
Genes, Tumor Suppressor
Humans
Lymph Nodes
Methylation
Neoplasm Metastasis
Polymerase Chain Reaction
Promoter Regions, Genetic
Cadherins
DNA

Figure

• 

  Fig. 1 E-cadherin expression by immunohistochemical stain; A shows strong membranous expression of E-cadherin, along the intercellular boundaries (grade I endometrial carcinoma). B shows remarkable loss of immunoreactivity (grade III endometrial carcinoma).

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  Fig. 2 Methylation analysis of E-cadherin promoter gene. The first case showed unmethylated. Case 43 and case 44 showed hypermethylated. U: unmethylated lane, M: methylated lane.

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