p16, Ki-67, and BD ProEX™C immunostaining: a practical approach for diagnosis of cervical intraepithelial neoplasia
p16, Ki-67, and BD ProEX™C immunostaining: a practical approach for diagnosis of cervical intraepithelial neoplasia
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DOI：
10.1016/j.humpath.2008.12.005
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发表时间：
2009-07-01
期刊：
影响因子：
3.3
通讯作者：
Bose, Shikha
中科院分区：
文献类型：
--
作者：
Walts, Ann E.;Bose, Shikha
p16、Ki-67和BD ProEx（TM）C（TriPath Imaging，Inc.，Burlington，NC）均被证明在人乳头瘤病毒相关宫颈上皮内瘤变的诊断和分级中是有帮助的。然而，在日常实践中没有关于其使用的明确准则。本研究旨在评价3种染色剂单独使用和联合使用的有效性，以确定诊断宫颈上皮内瘤变的最有用策略，并为染色模式不一致的情况提供指导。采用p16、Ki-67和BD ProEx（TM）C抗体对136例福尔马林固定石蜡包埋的宫颈样本的连续切片进行免疫染色，其中39例为良性反应性，46例为低度宫颈上皮内瘤变（CIN I/人乳头瘤病毒），51例为高度宫颈上皮内瘤变（CIN II/III）。在70例病例中提供了高危人乳头瘤病毒检测结果。根据在良性反应性、低度宫颈上皮内瘤变和高度宫颈上皮内瘤变病变中最常见的免疫染色模式，分别将免疫染色模式指定为阴性、中度和强阳性。所有3种染色的一致性染色模式正确识别了良性反应、低度宫颈上皮内瘤变和高度宫颈上皮内瘤变病例。p16是最敏感和最特异的个体染色（敏感性，33%;特异性，93%;阳性预测值[PPV]，81%;阴性预测值[NPV]，58%）。进行所有3种免疫染色并使用任何2种免疫染色的一致结果提高了诊断准确性（灵敏度，35%;特异性，98%; PPV，93%; NPV，67%）。然而，一个显着比例的低度宫颈上皮内瘤变病例显示异常染色模式，52%染色阴性和9%染色强阳性。染色呈阴性的低度宫颈上皮内瘤变病例更有可能为高危人乳头瘤病毒阴性，而染色呈强阳性的病例则为高危人乳头瘤病毒阳性。仅当p16和BD ProEx（TM）C产生不一致的结果时，先进行p16和BD ProEx（TM）C，然后进行Ki-67，以降低的成本提供了类似的诊断准确性，因为只有三分之一的病例需要额外的染色。(C)2009爱思唯尔公司All rights reserved.
p16, Ki-67, and BD ProEx (TM) C (TriPath Imaging, Inc., Burlington, NC) have each been shown to be helpful adjuncts in the diagnosis and grading of human papillomavirus-associated cervical intraepithelial neoplasia. However, no clear guidelines are available regarding their use in routine practice. This study was designed to evaluate the efficacy of the 3 stains alone and in combinations to determine the most useful strategy in the diagnosis of cervical intraepithelial neoplasia and provide guidance in instances with discordant staining patterns. Serial sections of 136 formalin-fixed paraffin-embedded cervical samples with consensus diagnoses of 39 benign-reactive, 46 low-grade cervical intraepithelial neoplasia (CIN I/human papillomavirus), and 51 high-grade cervical intraepithelial neoplasia (CINII/III) were immunostained using p16, Ki-67, and BD ProEx (TM) C antibodies. Results of high-risk human papillomavirus testing were available in 70 cases. Immunostaining patterns were designated as negative, intermediate, and strongly positive based on the patterns observed most commonly in benign-reactive, low-grade cervical intraepithelial neoplasia, and high-grade cervical intraepithelial neoplasia lesions, respectively. A concordant staining pattern with all 3 stains correctly identified benign-reactive, low-grade cervical intraepithelial neoplasia, and high-grade cervical intraepithelial neoplasia cases. p16 was the most sensitive and specific individual stain (sensitivity, 33%; specificity, 93%; positive predictive value [PPV], 81%; negative predictive value [NPV], 58%). performing all 3 immunostains and using concordant results of any 2 improved diagnostic accuracy (sensitivity, 35%; specificity, 98%; PPV, 93%; NPV, 67%). However, a significant proportion of low-grade cervical intraepithelial neoplasia cases showed aberrant staining patterns with 52% staining negative and 9% staining strongly positive. Low-grade cervical intraepithelial neoplasia cases with the negative staining pattern were more likely to be negative for high-risk human papillomavirus, whereas those showing the strongly positive staining pattern were high-risk human papillomavirus positive. performing p16 and BD ProEx (TM) C initially followed by Ki-67 only when p16 and BD ProEx (TM) C yielded discordant results provided similar diagnostic accuracy at reduced cost because only one third of the cases required the additional stain. (C) 2009 Elsevier Inc. All rights reserved.