Division of Medical Women's Health, Department of Medicine, Staten Island University Hospital, Staten Island, New York 10305, USA.
Int J Gynecol Pathol. 2012 Jan;31(1):1-7. doi: 10.1097/PGP.0b013e3182230df7.
The diagnosis of cervical intraepithelial neoplasia (CIN) has low interobserver reproducibility. The pathogenesis of human papillomavirus (HPV) from infection to high-grade CIN is well understood. In benign lesions, HPV-DNA is often packaged into virions, whereas malignant transformation disrupts virion assembly. It is conceivable that if cervical lesions were exposed to endonuclease digestion, HPV virions would alter nuclear susceptibility to DNA degradation. We propose that susceptibility to endonuclease digestion can serve as a simple marker to identify CIN grade. From paraffin-embedded tissue blocks, condyloma accuminata, CIN I-III, and cervical carcinoma cases were identified. Sections were placed in a bath containing DNAse I for DNA digestion. Residual DNA was stained by a Feulgen process. Endonuclease-resistant DNA (erDNA) staining was correlated to disease grade. In addition, 10 HPV (+) patients whose infection regressed and 8 whose infection progressed to CIN II or above had their initial HPV lesions stained for erDNA. erDNA was observed in 81% condylomas and 80% CIN I cases. All CIN II, III, and cancer cases were endonuclease sensitive with 100% of lesions showing no staining. Eighty percent of HPV lesions that regressed had erDNA staining, whereas 75% lesions that progressed had no erDNA staining. The spectrum of cervical disease caused by HPV has different susceptibilities to endonuclease digestion, which may aid in the diagnosis of CIN. Furthermore, in our small pilot study, erDNA status was associated with the clinical outcomes. Prospective studies are needed to confirm this observation. erDNA status is a promising novel biomarker.
宫颈上皮内瘤变（CIN）的诊断观察者间重复性低。人乳头瘤病毒（HPV）从感染到高级别 CIN 的发病机制已被充分理解。在良性病变中，HPV-DNA 常被包装成病毒颗粒，而恶性转化则破坏了病毒颗粒的组装。可以想象，如果宫颈病变暴露于内切酶消化，HPV 病毒颗粒会改变核对 DNA 降解的敏感性。我们提出，对内切酶消化的敏感性可以作为识别 CIN 分级的简单标志物。从石蜡包埋组织块中鉴定出尖锐湿疣、CIN I-III 和宫颈癌病例。将切片置于含有 DNAse I 的浴中进行 DNA 消化。用 Feulgen 法染色残留的 DNA。将内切酶抗性 DNA（erDNA）染色与疾病分级相关联。此外，对 10 例 HPV（+）感染消退的患者和 8 例感染进展为 CIN II 或以上的患者，对其初始 HPV 病变进行 erDNA 染色。erDNA 见于 81%的尖锐湿疣和 80%的 CIN I 病例。所有 CIN II、III 和癌症病例均对内切酶敏感，100%的病变无染色。80%消退的 HPV 病变有 erDNA 染色，而 75%进展的病变没有 erDNA 染色。HPV 引起的宫颈病变谱对内切酶消化具有不同的敏感性，这可能有助于 CIN 的诊断。此外，在我们的小型试点研究中，erDNA 状态与临床结果相关。需要进行前瞻性研究来证实这一观察结果。erDNA 状态是一种很有前途的新型生物标志物。
