Shi Jianhui, Liu Haiyan, Wilkerson Myra, Huang Yajue, Meschter Steven, Dupree William, Schuerch Conrad, Lin Fan
Department of Laboratory Medicine, Geisinger Medical Center, Danville, PA 17822, USA.
Hum Pathol. 2007 Sep;38(9):1335-44. doi: 10.1016/j.humpath.2007.01.025. Epub 2007 May 18.
p16INK4a has been shown to be overexpressed in nearly all high-grade squamous intraepithelial lesions (HSILs). Other cell-cycle regulators, such as minichromosome maintenance protein 2 (MCM2), DNA topoisomerase IIalpha (TOP IIA), and ProE(X) C (a cocktail of MCM2 and TOP IIA), have also demonstrated some value in identifying squamous intraepithelial lesions. Data on direct comparison of those cell regulatory proteins in the detection of squamous intraepithelial lesions, with a focus on low-grade squamous intraepithelial lesions (LSILs), are limited. We immunohistochemically evaluated the diagnostic value of p16, MCM2, TOP IIA, ProE(X) C, and a cocktail of p16 and ProE(X) C in 62 cervical biopsy specimens, including 14 cases of benign squamous mucosa (group 1), 34 cases of LSILs (group 2), and 14 cases of HSILs (group 3). The staining intensity and distribution were recorded. The results demonstrated that positive staining for p16 and the p16/ProE(X) C was observed in 100% of cases in group 3, whereas 79%, 86%, and 79% of cases were positive for CM2, TOP IIA, and ProE(X) C, respectively. ProE(X) C and the p16/ProE(X) C showed positive staining in 94% and 100% of cases in group 2, respectively. In contrast, immunoreactivity for p16, MCM2, and TOP IIA was detected in only 76% of cases in group 2. Importantly, all 8 p16-negative cases in group 2 were positive for p16/ProE(X) C (P = .003). Our data indicate that (1) p16 is a more sensitive and specific marker for identifying HSILs; (2) ProE(X) C is a better marker for the detection of LSILs; and (3) p16/ProE(X) C provides the highest diagnostic value for the detection of both HSILs and LSILs.
p16INK4a已被证明在几乎所有高级别鳞状上皮内病变（HSIL）中均有过表达。其他细胞周期调节因子，如微小染色体维持蛋白2（MCM2）、DNA拓扑异构酶IIα（TOP IIA）以及ProE(X)C（MCM2和TOP IIA的混合物），在识别鳞状上皮内病变方面也显示出一定价值。关于这些细胞调节蛋白在检测鳞状上皮内病变（尤其是低级别鳞状上皮内病变（LSIL））方面的直接比较数据有限。我们采用免疫组织化学方法评估了p16、MCM2、TOP IIA、ProE(X)C以及p16与ProE(X)C的混合物在62例宫颈活检标本中的诊断价值，其中包括14例良性鳞状黏膜（第1组）、34例LSIL（第2组）和14例HSIL（第3组）。记录染色强度和分布情况。结果显示，第3组100%的病例p16和p16/ProE(X)C呈阳性染色，而CM2、TOP IIA和ProE(X)C的阳性病例分别为79%、86%和79%。ProE(X)C和p16/ProE(X)C在第2组中分别有94%和100%的病例呈阳性染色。相比之下，第2组中仅76%的病例p16、MCM2和TOP IIA呈免疫反应性。重要的是，第2组中所有8例p16阴性病例p16/ProE(X)C均为阳性（P = 0.003）。我们的数据表明：（1）p16是识别HSIL更敏感且特异的标志物；（2）ProE(X)C是检测LSIL更好的标志物；（3）p16/ProE(X)C在检测HSIL和LSIL方面具有最高的诊断价值。
