Upregulation of telomerase (hTERT) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus, virus persistence, or disease outcome in cervical cancer
Upregulation of telomerase (hTERT) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus, virus persistence, or disease outcome in cervical cancer
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DOI：
10.1002/dc.20554
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发表时间：
2006-11-01
影响因子：
1.3
通讯作者：
Syrjanen, K.
中科院分区：
文献类型：
--
作者：
Branca, M.;Giorgi, C.;Syrjanen, K.
端粒酶的激活和端粒的维持是细胞永生所必需的，代表了癌症进展的限速步骤。已知高危人乳头瘤病毒（HPV）的E6癌蛋白可激活端粒酶，但其在CIN病变中的表达及其在宫颈癌（CC）中的预后价值仍不完全清楚。作为我们HPV-病原学研究的一部分，我们使用免疫组织化学（IHC）染色检测了150例cc和152例CIN病变的端粒酶逆转录酶，并使用三组引物(MY09/11, GP5(+)/ GP6（+）进行了HPV PCR检测。防晒系数)。所有SCC患者的随访数据均可获得，67例CIN病变在锥形治疗后用连续PCR检测HPV。hTERT的表达与CIN分级平行升高，在向CIN3过渡时显著上调（OR 18.81; 95% Cl 8.48-41.69; P = 0.0001）。hTERT阳性表达是CIN的90%特异性指标，PPV为98.7%，但敏感性（57.5%）和NPV（14.3%）较低。hTERT表达也与HR-HPV显著相关，OR为3.38 (95% CI 1.90-6.02; P = 0.0001)，但这种关联被组织学分级混淆（Mantel-Haenszel common OR = 1.83; 95% CI 0.92-3.79; P = 0.086）。hTERT的表达并不能预测CIN治疗后HR-HPV的清除/持续，在单因素或多因素生存分析中，它也不是宫颈癌的预后预测因子。结论：hTERT的上调与HR-HPV密切相关，这是由于E6癌蛋白的激活。hTERT是宫颈癌发生的晚期标志物，与CIN3进展显著相关。从理论上讲，hTERT检测（显示高SP和PPV）与另一种显示高SE和高NPV的检测（例如HPV的杂交捕获2）相结合，应该提供一种能够高效检测CIN病变的理想筛查工具。(c) 2006 Wiley-Liss, Inc。
Telomerase activation and telomere maintenance are essential for cell immortalization and represent a rate-limiting step in cancer progression. The E6 oncoprotein of high-risk human papillomavirus (HPV) is known to activate telomerase, but its expression in CIN lesions and its prognostic value in cervical cancer (CC) are still incompletely understood.As part of our HPV-PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using immunohistochemical (IHC) staining for hTERT (telomerase reverse transcriptase), and tested for HPV using PCR with three primer sets (MY09/11, GP5(+)/ GP6(+). SPF). Follow-up data were available from all SCC patients, and 67 CIN lesions had been monitored with serial PCR for HPV after cone treatment.Expression of hTERT was increased in parallel with the grade of CIN, with major up-regulation upon transition to CIN3 (OR 18.81; 95% Cl 8.48-41.69; P = 0.0001). Positive hTERT expression was 90% specific indicator of CIN, with 98.7% PPV, but suffers from low sensitivity (57.5%) and NPV (14.3%). hTERT expression was also significantly associated to HR-HPV with OR 3.38 (95% CI 1.90-6.02; P = 0.0001), but this association was confounded by the histological grade (Mantel-Haenszel common OR = 1.83; 95% CI 0.92-3.79; P = 0.086). Expression of hTERT did not predict clearance/persistence of HR-HPV after treatment of CIN, and it was not a prognostic predictor in cervical cancer in univariate or multivariate survival analysis.It was concluded that up-regulation of hTERT was closely associated with HR-HPV, due to activation by the E6 oncoprotein. hTERT is a late mark-er of cervical carcinogenesis, significantly associated with progression to CIN3. Theoretically, a combination of hTERT assay (showing high SP and PPV) with another test showing high SE and high NPV (e.g. Hybrid Capture 2 for HPV), should provide an ideal screening tool capable of high-performance detection of CIN lesions. (c) 2006 Wiley-Liss, Inc.