Predictive value of p16INK4a, Ki-67 and ProExC immuno-qualitative features in LSIL progression into HSIL
Predictive value of p16INK4a, Ki-67 and ProExC immuno-qualitative features in LSIL progression into HSIL
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p16INK4a、Ki-67 和 ProExC 免疫定性特征对 LSIL 进展为 HSIL 的预测价值
DOI：
10.3892/etm.2020.8496
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发表时间：
2020-04-01
影响因子：
2.7
通讯作者：
Wang, Jintao
中科院分区：
文献类型：
--
作者：
Ding, Ling;Song, Li;Wang, Jintao
当前的巢式病例对照研究旨在探讨细胞周期蛋白依赖性激酶抑制剂 2A (p16(INK4a))、增殖标记物 Ki-67 (Ki-67) 以及含有针对拓扑异构酶 II α (TOP2A) 和微型染色体维持 2 (MCM2) 蛋白的抗体的免疫组织化学混合物的预后价值 (ProExC) 免疫定性特征可预测低度鳞状上皮内病变 (LSIL) 进展。对92例LSIL患者进行为期2年的随访，其中高度鳞状上皮内病变（HSIL）或持续性LSIL患者为病例组，自然消退者为对照组。采用流通杂交和基因芯片评估人乳头瘤病毒（HPV）的感染状态，同时通过免疫组织化学检测LSIL患者活检组织中p16（INK4a）、Ki-67和ProExC的表达。所有数据均在随访开始时收集，并通过组织病理学检查诊断患者结果。为了分析 LSIL 进展的危险因素，进行了敏感性、特异性、阳性-阴性预测值 (PPV-NPV)、阳性-阴性似然比 (PLR-NLR)、Youden 指数 (YI) 和多项 Logistic 回归分析。发现进展组中 p16(INK4a)、Ki-67 和 ProExC 的表达率高于持续组和消退组。只有p16(INK4a)表达与高危HPV感染显着相关。对于预测 HSIL，p16(INK4a) 染色最敏感，但 Ki-67 染色最具特异性。在本研究中，YI 的 p16(INK4a) 表达最高 (42.1%)，其次是 ProExC (39.5%) 和 Ki-67 (28.3%)。然而，ProExC 的表达被发现是 LSIL 进展为 HSIL 的独立危险因素。总之，虽然 p16(INK4a)、Ki-67 和 ProExC 的免疫组织化学染色可用于预测 HSIL 进展，但只有 ProExC 表达可以作为 LSIL 进展的独立危险因素。
The current nested case-control study was conducted to explore the prognostic value of cyclin-dependent kinase inhibitor 2A (p16(INK4a)), marker of proliferation Ki-67 (Ki-67) and immunohistochemical cocktail containing antibodies directed against topoisomerase II alpha (TOP2A) and minichromosome maintenance 2 (MCM2) proteins (ProExC) immuno-qualitative features to predict low-grade squamous intraepithelial lesion (LSIL) progression. A total of 92 LSIL patients were followed-up for 2 years, where those with high-grade squamous intraepithelial lesion (HSIL) or persistent LSIL were designated as the case group and those who spontaneously regressed were designated as the control group. The infection status of human papillomavirus (HPV) was evaluated using flow-through hybridization and gene chip, whilst the expression of p16(INK4a), Ki-67 and ProExC were tested in LSIL patient biopsies by immunohistochemistry. All data were collected at the beginning of the follow-up and patient outcomes were diagnosed by histopathological examination. To analyze the risk factors for LSIL progression, sensitivity, specificity, positive-negative predictive value (PPV-NPV), positive-negative likelihood ratio (PLR-NLR), Youden's index (YI) and multinomial logistic regression analysis was performed. The expression rates of p16(INK4a), Ki-67, and ProExC were found to be higher in the progression group compared with those in the persistence and regression groups. Only p16(INK4a) expression significantly associated with high-risk HPV infection. With respect to predicting HSIL, p16(INK4a) staining was the most sensitive but Ki-67 staining was found to be the most specific. YI was the highest (42.1%) for p16(INK4a) expression in the present study, followed by ProExC (39.5%) and Ki-67 (28.3%). However, the expression of ProExC was found to be an independent risk factor for LSIL progression into HSIL. In conclusion, whilst immunohistochemical staining for p16(INK4a), Ki-67, and ProExC can be used to predict HSIL progression, only ProExC expression can be applied an independent risk factor for LSIL progression.