Zhang Jing-jie, Ouyang Tao, Wan Wen-hui, Deng Guo-ren
Department of Surgrey, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Zhonghua Zhong Liu Za Zhi. 2007 Aug;29(8):609-13.
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.
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.
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.
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.
研究APC和E-钙黏蛋白基因启动子高甲基化作为肿瘤标志物，并探讨血清和肿瘤组织中游离肿瘤相关DNA与临床病理参数的相关性。评估其在早期诊断、预测治疗效果及监测复发方面的可行性。
2002年3月至2002年8月在北京肿瘤医院招募84例接受手术的乳腺癌患者。采用甲基化特异性PCR（MSP）检测肿瘤组织、癌旁正常组织及外周血血清中E-钙黏蛋白和APC基因的异常甲基化。选取10例乳腺良性疾病患者作为对照组。
肿瘤组织中E-钙黏蛋白和APC基因启动子高甲基化阳性率分别为52.4%和45.2%，配对血清中分别为33.3%和31.0%。血清中游离DNA的异常甲基化在肿瘤组织中呈现相同变化。血清和肿瘤样本中E-钙黏蛋白和APC高甲基化显著相关（E-钙黏蛋白P<0.001；APC P=0.002）。血清中E-钙黏蛋白和APC基因游离DNA甲基化检测的敏感性分别为63.6%和63.2%，特异性分别为100%和95.7%。癌组织和血清中的异常甲基化与患者的年龄、肿瘤分期、肿瘤大小、组织学类型及受体等临床病理参数均无相关性。癌旁正常组织及对照组血清中均未发现异常甲基化。
约三分之一的乳腺癌患者癌组织和血清中可检测到相同的异常甲基化，且与肿瘤分期无关。术后血清中的异常甲基化可消失。结果提示该方法可能对乳腺癌的早期诊断、治疗效果评估及复发监测可行。
