Genomic amplification of the human telomerase gene (TERC) in pap smears predicts the development of cervical cancer
Genomic amplification of the human telomerase gene (TERC) in pap smears predicts the development of cervical cancer
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DOI：
10.1016/s0002-9440(10)62341-3
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发表时间：
2005-04-01
影响因子：
6
通讯作者：
Ried, T
中科院分区：
文献类型：
--
作者：
Heselmeyer-Haddad, K;Sommerfeld, K;Ried, T
浸润性宫颈癌几乎总是携带额外的染色体臂3Q拷贝，导致人类端粒酶基因(TERC)的获得。这为开发多色荧光原位杂交(FISH)探针集作为直接检测巴氏涂片中TERC收益的诊断工具提供了理论基础。我们以前使用该探针组显示宫颈上皮内瘤变(CIN)2和CIN3病变可以与正常组织、未确定意义的不典型鳞状细胞(ASCUS)和CIN1区分开来，灵敏度和特异度超过90%，独立于细胞形态学评估。在目前的研究中，我们探讨了3Q的增加和TERC的扩增是否可以预测从CIN1/CIN2到CIN3的进展和浸润性癌。我们将我们的探针组应用于一系列59例先前染色的巴氏涂片，对于这些涂片，重复巴氏涂片和临床随访是可用的。这些样本包括进展到CIN3的CIN1/CIN2病变(进展者)，自发退化的CIN1/CIN2病变(退化者)，以及后来发展为CIN3或宫颈癌的妇女的正常巴氏涂片。在这里，我们表明，进展者表现出3Q的增益，而退化者没有表现出这种遗传异常。这些数据表明，从CIN1/CIN2到CIN3的转变需要3Q增益，并且它预测了进展。值得注意的是，在细胞学正常的巴氏涂片中，33%被诊断为CIN3或浸润性宫颈癌的妇女在较短的潜伏期后3Q增加。我们的试验预测从CIN1/CIN2到CIN3进展的敏感性为100%，特异性，即预测回归的特异性为70%。我们的结论是，在常规收集的巴氏涂片中检测3Q增益和TERC扩增有助于识别具有高进展风险的低级别病变，并有助于减少细胞学筛查的假阴性。
Invasive cervical carcinomas almost invariably carry extra copies of chromosome arm 3q, resulting in a gain of the human telomerase gene (TERC). This provided the rationale for the development of a multicolor fluorescence in situ hybridization (FISH) probe set as a diagnostic tool for the direct detection of TERC gains in Pap smears. We previously used this probe set to show that cervical intraepithelial neoplasia (CIN) 2 and CIN3 lesions could be distinguished from normal samples, atypical squamous cell of undetermined significance (ASCUS) and CIN1, with a sensitivity and specificity exceeding 90%, independent of the cytomorphological assessment. In the current study, we explored whether gain of 3q and amplification of TERC could predict progression from CIN1/CIN2 to CIN3 and invasive carcinoma. We applied our probe set to a series of 59 previously stained Pap smears for which repeat Pap smears and clinical follow-up were available. The samples included CIN1/CIN2 lesions that progressed to CIN3 (progressors), CIN1/CIN2 lesions that regressed spontaneously (regressors), and normal Pap smears from women who subsequently developed CIN3 or cervical cancer. Here, we show that progressors displayed a gain of 3q whereas none of the regressors showed this genetic aberration. These data suggest that 3q gain is required for the transition from CIN1/CIN2 to CIN3 and that it predicts progression. Of note, 3q gain was found in 33% of cytologically normal Pap smears from women who were diagnosed with CIN3 or invasive cervical carcinoma after a short latency. The sensitivity of our test for predicting progression from CIN1/CIN2 to CIN3 was 100% and the specificity, ie, the prediction of regression, was 70%. We conclude that the detection of 3q gain and amplification of TERC in routinely collected Pap smears can assist in identifying low-grade lesions with a high progression risk and in decreasing false-negative cytological screenings.