Cadherin methylation may provide prognostic marker for cervical cancer

The detection of hypermethylated cadherins in the serum of patients with cervical cancer is associated with an increased risk of disease progression, an Austrian research team reports in a fast-track article in the March 20th issue of the International Journal of Cancer.

In the same issue of the Journal, Japanese researchers report that E-cadherin methylation may differ in gastric cancers depending on the tumors’ association with Epstein-Barr virus (EBV).Previous research has shown that reduced tumor expression of E- cadherin, associated with cancer aggressiveness, is related to methylation status of the E-cadherin gene (see Reuters Health article, April 18, 2003).The Austrian team, led by Dr. Martin Widschwendter at Innsbruck University Hospital, determined methylation status of E- and H-cadherin genes in serum samples of 93 women newly diagnosed with cervical cancer, prior to initial treatment.Aberrant promoter hypermethylation of E-cadherin and of H-cadherin was observed in 39 (42%) and 4 (4%) patients, respectively. Median disease-free survival for methylation-negative patients was 4.3 years, versus 1.2 years for those with methylation positive cadherins (p = 0.03). There was also a trend toward worse overall survival (p = 0.09).In multivariate analysis, cadherin methylation was associated with a 2.5-fold increased relative risk of relapse or death (p = 0.005 for each).Detection of aberrant cadherin methylation “may be of potential use as a marker for selecting cervical cancer patients at high risk for relapse who could benefit from additional systemic therapy,” Dr. Widschwendter’s group suggests. They also recommend that this approach be investigated for use in other types of malignancies.Dr. Masashi Fukayama at the University of Yamanashi and colleagues in Japan examined the relationship between E-cadherin methylation in EBV-positive and EBV-negative gastric cancer in 103 tissue samples. Twenty-two cases were associated with EBV, while 81 cases were EBV-negative.Aberrant methylation of E-cadherin was more frequently observed in EBV-positive tumors (21/22) than in EBV-negative tumors (45/81, p = 0.003).In the 41 EBV-negative gastric carcinomas of the intestinal type, hypermethylation was significantly correlated with lymph node metastasis (p = 0.0038). A similar correlation was not observed in EBV-negative cancers of the diffuse type.Because the significance of aberrant methylation of E-cadherin differs between EBV-positive and EBV-negative gastric carcinoma, the authors conclude that the “recognition of this type of gastric carcinoma is critical for the evaluation of carcinogenesis of the stomach.”(Source: Int J Cancer 2004;109:163-166,194-199: Reuters Health: Oncolink: April 2004)