OBJECTIVETo detect the gene promoter methylation, mRNA and protein expression levels of E-cadherin and beta-catenin in primary and metastatic tumor samples of nasopharyngeal carcinoma (NPC), and to investigate the mechanism of invasion and metastasis of neoplastic cell in NPC.

METHODSTwenty-one patients with NPC were studied. The samples of primary tumor and paired lymph node metastatic tumor were collected and examined for aberrant gene promoter methylation in E-cadherin by DNA Methylation-specific polymerase chain reaction (MSP). Reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical staining were adopted to detect mRNA and protein levels of E-cadherin and beta-catenin.

RESULTS(1) The gene promoter methylation in E-cadherin was 52.4% (11/21) in primary tumor of NPC, and 80.9% (17/21) in lymph node metastatic tumor, which existed significant difference (P < 0.05). (2) In primary tumor, about 80% (0 approximately 100%) neoplastic cells expressed E-cadherin protein on the average, which was significantly higher than that of metastatic tumor (50% on the average, P = 0.004). The expression levels of beta-catenin protein were high in both primary and metastatic tumors, but with no statistic difference (P = 0.698). (3) By Western blotting analysis, the relative intensity of protein expression in E-cadherin was significantly higher in primary tumor (206.7 +/- 32.7) compared to that of metastatic tumor (65.0 +/- 15.9), while the expression of beta-catenin protein showed no difference between them (P = 0.754). (4) mRNA expression level of E-cadherin was higher in primary tumor than that of metastatic tumor.No remarkable difference was found for the mRNA expression of beta-catenin.

CONCLUSIONS(1) Downregulation of mRNA and protein expression of E-cadherin may play a critical role in neoplastic cell invasion and metastasis in NPC. The aberrant promoter methylation of E-cadherin may ultimately alter the mobility and scattering of tumor cells in NPC. (2) Downregulation of E-cadherin alone may be enough for the tumor cell to lose intercellular adhesions which results in tumor cell invasion and metastasis. However, mutant beta-catenin could also involve in this progress. (3) The detection of gene promoter hypermethylation of E-cadherin should be evaluated in the screening and surveillance of NPC.