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在细胞学轻度异常且 HR-HPV 阳性的液基薄层细胞学标本中 hTERC 的应用。

Application of hTERC in thinprep samples with mild cytologic abnormality and HR-HPV positive.

机构信息

Women's Reproductive Health Laboratory of Zhejiang Province, China.

出版信息

Gynecol Oncol. 2011 Jan;120(1):73-83. doi: 10.1016/j.ygyno.2010.10.007. Epub 2010 Oct 28.

Abstract

OBJECTIVE

Amplification of hTERC is found to be an important genetic event in the progression from cervical dysplasia to cervical cancer. The hTERC value in predicting high-grade cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC), in high-risk HPV (HR-HPV) positive thinprep samples with atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL) was explored in this study.

METHODS

A total of 300 thinprep cytology specimens (129 of ASC-US, 82 of LSIL, and 89 of ASC-H) with positive HR-HPV DNA was detected by a two-probe dual-color FISH panel, targeting hTERC and the centromeric region of chromosome 3 (CSP3). Using >2 signals for hTERC together with ≥2 signals for CSP3 to define abnormal nucleus, and the cutoff value was set at 6.5 per random 200 nuclei displayed increased hTERC signals and/or tumor ploidy. Statistical analyses were based on histologic findings of colposcopy biopsies, allowing CIN2 or worse (CIN2+) as the positive criterion.

RESULTS

The FISH results were systematically analyzed among groups, based on histologic diagnosis, cytologic finding, HR-HPV viral load, and age status. hTERC presented good consistency with histology, and had satisfactory sensitivity, specificity, and accuracy among different groups, with less difference intergroup. The individual hTERC positive nuclei ratio was generally increased with severity of the cervical lesions.

CONCLUSIONS

hTERC could be a stable predictor in assuring the risk of high-grade CIN in women with mild cytologic abnormality and positive HR-HPV, and the individual positive nuclei ratio of it might be helpful in identifying morbid grade for cervical lesions.

摘要

目的

在宫颈癌前病变进展为宫颈癌的过程中,发现 hTERC 扩增是一个重要的遗传事件。本研究旨在探讨 hTERC 值在预测高危型 HPV(HR-HPV)阳性液基细胞学标本中不典型鳞状细胞(ASC-US)、低度鳞状上皮内病变(LSIL)或非典型鳞状细胞不能明确意义(ASC-H)患者中高级别宫颈上皮内瘤变(CIN)或鳞状细胞癌(SCC)的价值。

方法

采用两探针双色荧光原位杂交(FISH)技术检测了 300 例 HR-HPV 阳性的液基细胞学标本(129 例 ASC-US、82 例 LSIL 和 89 例 ASC-H),该技术靶向 hTERC 和 3 号染色体着丝粒(CSP3)。采用 >2 个 hTERC 信号和/或 ≥2 个 CSP3 信号来定义异常核型,同时将 hTERC 信号值的截断值设为 6.5,即随机选择 200 个细胞核中 hTERC 信号值增加和/或肿瘤倍体的细胞核数>6.5。统计学分析基于阴道镜活检的组织学发现,以 CIN2 或更高级别病变(CIN2+)作为阳性标准。

结果

基于组织学诊断、细胞学发现、HR-HPV 病毒载量和年龄状态对各组进行了 FISH 结果的系统分析。hTERC 与组织学具有良好的一致性,在不同组间具有较高的敏感性、特异性和准确性,组间差异较小。随着宫颈病变程度的加重,hTERC 阳性核的比例普遍增加。

结论

hTERC 可作为预测 HR-HPV 阳性、细胞学轻度异常的女性发生高级别 CIN 风险的稳定指标,hTERC 阳性核的比例可能有助于识别宫颈病变的严重程度。

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