Hypermethylation in promoter region of E-cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinoma

BACKGROUND Loss of E-cadherin expression is associated with aberrant 5′ CpG island methylation in various tumors. METHODS The authors analyzed the methylation status and immunohistochemical expression of E-cadherin in 142 endometrial tissues, consisting of 21 normal endometria, 17 endometrial hyperplasias, and 104 endometrial carcinomas. RESULTS All normal endometria and endometrial hyperplasias showed positive staining of E-cadherin, and methylation of the E-cadherin gene was not detected in any samples. In endometrial carcinoma, the positive ratio of methylation was higher and was associated with tumor dedifferention and myometrial invasion. In G1 endometrial adenocarcinomas, 66.7% showed positive staining and 33.3% showed heterogeneous staining. Methylation of the E-cadherin gene was detected in 15.6%. In G2 tumors, 19.0% showed positive staining, 69.0% showed heterogeneous staining and 11.9% showed negative staining. Methylation of the E-cadherin gene was found in 50.0%. In G3 tumors, 9.1% showed positive staining, 54.5% showed heterogeneous staining and 36.3% showed negative staining. Methylation of the E-cadherin gene was found in 81.8% of the tumors. Of the samples with no-myometrial invasion, 23.1% had methylation. In those with invasion in less than half of the myometrium, 28.6% did and in those with invasion of half or more of the myometrium, 55.6% had methylation. Of samples that did not have lymph node metastasis, 33.7% had methylation, whereas of samples that had lymph node metastasis, 60.0% had methylation. CONCLUSIONS This is the first report to analyze methylation of the E-cadherin gene promoter of endometrial carcinoma and the evidence suggests that methylation of the E-cadherin gene occurs in association with the acquisition of invasive capacity. Cancer 2003;97:1002–9. © 2003 American Cancer Society. DOI 10.1002/cncr.11157