Methylation status of the fragile histidine triad and E-cadherin genes in plasma of cervical cancer patients

Recent evidence suggests that tumor cells may release DNA into the serum and plasma of afflicted cancer patients. However, no report existed regarding the methylation status of the fragile histidine triad (FHIT) and E-cadherin genes in plasma samples of cervical cancer patients. Methylation-specific PCR (MSP) was employed to examine CpG island methylation of the FHIT and E-cadherin genes in 151 pretreatment plasma samples and 30 tumor tissue samples from cervical cancer patients. MSP products were cloned and sequenced. CpG island methylation of the FHIT and E-cadherin genes was detected in 30.46% and 39.74% of plasma samples, respectively, and in 53.33% and 60.0% of tissue samples, respectively. The total concordance rate of methylation between plasma samples and tissue samples in FHIT gene was 80.00% and that in E-cadherin gene was 76.66%. At least one of the two methylated genes was detected in 56.29% of plasma samples and 76.7% of tissue samples. The presence of both methylated genes was detected in 13.9% of plasma samples and 36.67% of tissue samples. We found that the higher the clinical stage and histologic grade, the higher the rate of methylation in both genes in plasma samples. CpG island methylation of the FHIT and E-cadherin genes is present in plasma of cervical cancer patients. Using the two genes as markers simultaneously may allow clinicians to diagnose and evaluate the effect of treatment earlier and using fewer invasive procedures.