E-cadherin promoter hypermethylation may contribute to protein inactivation in pterygia

PURPOSE Our recent reports indicated that the molecular changes of pterygia are similar to tumor cells. We believe that pterygia may have a similar mechanism in oncogenesis. Many studies have revealed that E-cadherin associated protein expression decreases in many tumors and pterygia. E-cadherin may be a marker for both tumor metastasis and prognosis. However, no studies have examined the reason for E-cadherin protein inactivation in pterygia. Therefore, this study aimed to analyze the association of E-cadherin promoter hypermethylation with protein inactivation in pterygial tissues. METHODS E-cadherin methylation-status and the expression of E-cadherin and beta-catenin protein were studied using methylation-specific PCR and immunohistochemistry, respectively, on 120 pterygial specimens and 30 normal conjunctivas. RESULTS Hypermethylation of E-cadherin gene promoter was detected in 32 (26.7%) of the 120 pterygial specimens. A total of 79 (65.8%) pterygial specimens tested positive for E-cadherin protein expression and 41 (34.2%) specimens tested negative. The E-cadherin staining was limited to the membrane of the epithelial layer. There was a reverse correlation between E-cadherin gene promoter hypermethylation and E-cadherin protein expression (p<0.0001). Aberrant localization of beta-catenin was higher in the E-cadherin negative group than in E-cadherin positive group. CONCLUSIONS Our study demonstrates E-cadherin gene promoter hypermethylation were associated with low or absent expression of E-cadherin. Moreover, loss of E-cadherin protein may contribute to aberrant localization of beta-catenin. These data provide evidence that methylation exists in pterygia and may play a role in their development.