尿液P16基因甲基化对浅表性膀胱移行细胞癌早期诊断的意义

Value of P16 gene methylation in urinary exfoliated cells for early diagnosis of superficial bladder transitional cell carcinoma

目的探讨P16基因甲基化在浅表性膀胱移行细胞癌发生早期的临床意义。方法取42例膀胱移行细胞癌组织及配对尿液标本,以其中9例的对侧正常膀胱黏膜组织作对照,采用甲基化特异性PCR方法检测P16基因CpG岛甲基化状态。结果35例肿瘤组织标本,18例P16基因CpG岛存在甲基化状态,占51.4%(18/35);尿液标本中,16例P16基因CpG岛存在甲基化状态,占45.7%(16/35)。Log istic回归分析显示年龄、性别、是否吸烟、合并其他疾病、肿瘤的临床分期和病理分型等因素对P16基因甲基化无影响(P>0.05)。20例浅表性膀胱移行细胞癌患者的尿液标本中发现P16基因甲基化10例,其配对的浅表性膀胱移行细胞癌组织中均检出P16基因甲基化,正常人和非尿路肿瘤患者尿液中未检出到P16基因甲基化,尿液P16基因甲基化在浅表性膀胱移行细胞癌中的阳性预测值和特异度均为100%,假阳性为0%,灵敏度为90.91%。正常人组和非尿路肿瘤组与浅表性膀胱移行细胞癌组尿液中P16基因甲基化比较差异有统计学意义(P<0.001),9例正常组织对照均未发现P16基因CpG岛甲基化。结论P16基因甲基化与年龄、性别、肿瘤的分级分期无相关性;尿液P16基因异常甲基化可成为浅表性膀胱移行细胞癌早期诊断的分子生物学标志。

Objective To investigate the clinical significance of P16 gene methylation in urinary exfoliated cells for early diagnosis of superficial bladder transitional ceil carcinoma （BTCC）. Methods A methylation-specific polymerase chain reaction （MSP） was performed to detect P16 gene CpG island methylation in the matched samples of tumor tissue and urine exfoliated cells from 35 cases of BTCC patients. The mucous membrane of urinary bladder in opposite side of the pathological changes was taken as the control in 9 of 35 cases. Results Methylation of P16 gene CpG island was demonstrated in 51.4% （18/35） of the tumor tissues,45.7% （16/35） of the urine exfoliated cells,respectively. Logistic regression revealed that the methylation was not related to the age, gender, tumor pathologic grade and clinical stage （P〉 0. 05）. The P16 gene methylation of urinary samples was detected in 10 out of 20 superficial BTCC patients. And the methylation also existed in the tumor tissues of the matched urine samples. The urine samples from the patients without urinary tumor or disorders showed no metbylation. Both the positive predictive value and specificity of the P16 gene methylation in the urinary exfoliated cells were 100. 0%. And the false positive and sensibility were 0 and 90. 9%, respectively. No P16 CpG island methylation was found in normal urothelium （9 cases）. The differences were statistically significant （P 〈0. 001 ）. Conclusion The methylation in urinary exfoliated cells may be used as a biomarker for early diagnostic of superficial BTCC.