[Detection of free tumor-related DNA in the serum of breast cancer patients].
OBJECTIVE
To study the APC and E-cadherin gene promoter hypermethylation as tumor marker and to investigate the correlation of free tumor-related DNA in serum and tumor tissue with clinicopathological parameters. Their feasibility in early diagnosis, predicting therapeutic effect and monitoring recurrence was evaluated.


METHODS
84 cases with operated breast cancer were recruited from March 2002 to August 2002 at Beijing Cancer Hospital. Aberrant methylation of E-cadherin and APC genes was detected in tumor tissues, adjacent normal tissues and peripheral blood serum by methylation-specific PCR (MSP). 10 cases with benign breast diseases were selected as control group.


RESULTS
The positive rate of promoter hypermethylation of E-cadherin and APC genes in tumor tissues was 52.4% and 45.2%, in the paired serum was 33.3% and 31.0%, respectively. Aberrant methylation of free DNA in serum presented the same alteration in tumor tissues. E-cadherin and APC hypermethylation in serum and tumor samples significantly correlated each other (E-cadherin P < 0.001; APC P = 0.002). The sensitivity of detection of free DNA methylation of E-cadherin and APC genes in serum was 63.6% and 63.2%, respectively. The specificity was 100% and 95.7%, respectively. There was no correlation for the aberrant methylation in cancer tissues and serum with the clinicopathological parameters of patients including age, tumor staging, tumor size, histological type and receptor. None of the aberrant methylation was found in adjacent normal tissues and control group serum.


CONCLUSIONS
The same aberrant methylation in cancer tissues and serum, not correlating with tumor staging, can be detected in about one third of breast cancer patients. The aberrant methylation in serum can disappear after operation. The results imply that this approach may be feasible for early diagnosis, evaluation of therapeutic effects and monitoring recurrence of breast cancers.
Zhang
Jing-jie
JJ
Department of Surgrey, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Ouyang
Tao
T
Wan
Wen-hui
WH
Deng
Guo-ren
GR
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D015820:Cadherins / Q000097:blood / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D005260:Female; D017491:Genes, APC; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity; D055815:Young Adult
D014408:Biomarkers, Tumor; D015820:Cadherins; D004273:DNA, Neoplasm