Upregulation of nuclear factor-κB (NF-κB) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus or disease outcome in cervical cancer
Upregulation of nuclear factor-κB (NF-κB) is related to the grade of cervical intraepithelial neoplasia, but is not an independent predictor of high-risk human papillomavirus or disease outcome in cervical cancer
复制标题
DOI：
10.1002/dc.20514
复制
发表时间：
2006-08-01
影响因子：
1.3
通讯作者：
Syrjanen, S.
中科院分区：
文献类型：
--
作者：
Branca, M.;Giorgi, C.;Syrjanen, S.
核因子 kappa B (NF-kappa B) 在控制多种基因功能方面具有关键功能，并且已被证明在许多人类癌症中被组成型激活。 NF-kappa B 与宫颈上皮内瘤变 (CIN) 病变中致癌人乳头瘤病毒 (HPV) 的分子联系及其在宫颈癌 (CC) 中的预后价值尚不完全清楚。作为我们 HPV-PathogenISS 研究的一部分，使用 NF-kappa B 免疫组织化学染色检查了一系列 150 个鳞状细胞癌 (SCC) 和 152 个 CIN 病变，并使用PCR 配备三台打印机（MY09/11、GP5(+)/ GP6(+). 和 SPF）。所有 SCC 患者均获得随访数据，并通过系列 PCR 监测了 67 个 CIN 病变在锥体治疗后的 HPV 清除/持续性。细胞质 NF-kappa B 表达与 CIN3/癌症相关，OR 为 3.55（95% CI，1.79-7.05），而核 NF-kappa B 表达的 OR 为 21.90（95% CI， 2.96-161.74) (P = 0.0001)。强核表达在 CC 中也是罕见事件 (8.8%)，但与高危人乳头瘤病毒 (HR-HPV) 检测相关，OR 2.15 (95% CI, 1.08-4.30) (P = 0.022)。然而，这种关联因组织学分级而混淆（Mantel-Haenszel 常见 OR = 1.46；95% CI， 0.70-3.03）（P = 0.308）。细胞质或细胞核 NF-kappa B 表达不能预测 CIN 治疗后 HR-HPV 的清除/持续，并且两者都没有被证明是 CC 的预后预测因子。细胞质 NF-kappa B 的过度表达与 CIN3 和癌症的进展显着相关。与此同时，NF-kappa B 的核表达仅略有增加，这可以通过 HR-HPV 逃离 NF-kappa B 转录控制的机制来解释，即 E7 介导的细胞质 NF-kappa B 核转位受损，以及 E6 条件减弱 NF-kappa B (p65) 依赖性转录活性。
Nuclear factor-kappa B (NF-kappa B) has a pivotal function in controlling a wide variety of gene functions, and has shown to be constitutively activated in many human cancers. The molecular links of NF-kappa B to oncogenic human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and its prognostic value in cervical cancer (CC) are incompletely understood.As part of our HPV-PathogenISS study, a series of 150 squamous-cell carcinomas (SCCs) and 152 CIN lesions were examined using immunohistochemical staining for NF-kappa B, and tested for HPV using PCR with three printer sets (MY09/11, GP5(+)/ GP6(+). and SPF). Follow-up data were available from all SCC patients, and 67 CIN lesions had been monitored with serial PCR for HPV clearance/persistence after cone treatment.Cytoplasmic NF-kappa B expression was associated with CIN3/cancer at OR 3.55 (95% CI, 1.79-7.05), while nuclear NF-kappa B expression had an OR of 21.90 (95% CI, 2.96-161.74) (P = 0.0001). Strong nuclear expression was a rare event (8.8%) also in CC, but it was related to high-risk human papillomavirus (HR-HPV) detection, with OR 2.15 (95% CI, 1.08-4.30) (P = 0.022), This association was confounded, however, by the histological grade (Mantel-Haenszel common OR = 1.46; 95% CI, 0.70-3.03) (P = 0.308). Cytoplasmic or nuclear NF-kappa B expression did not predict clearance/persistence of HR-HPV after treatment of CIN, and neither one proved to be a prognostic predictor in CC.Overexpression of cytoplasmic NF-kappa B is significantly associated with progression to CIN3 and cancer. This is paralleled by only a slight increase in nuclear expression of NF-kappa B, which could be explained by the mechanisms whereby HR-HPVs escape from the transcriptional control of NF-kappa B, i.e., E7-mediated impaired nuclear translocation of cytoplasmic NF-kappa B, and E6-conditioned attenuated NF-kappa B (p65)-dependent transcriptional activity.