Solano Felipe J, Rush Demaretta S, Wilkinson Edward J
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida.
Int J Gynecol Pathol. 2015 May;34(3):215-20. doi: 10.1097/PGP.0000000000000159.
Tissue biopsy following a pap test diagnosis of high grade squamous intraepithelial lesion (HSIL) sometimes fails to confirm the presence of a corresponding high grade cervical intraepithelial lesion (CIN 2-3), leading to confusion as to how best to manage the patient. It has been shown that these patients are still at higher risk for future detection of CIN 2-3 even if the initial biopsy fails to detect it. It has also been shown that immunohistochemical staining for p16INK4a can be reliably used as a surrogate marker for infection with high risk human papillomavirus in cervical samples, and that it can be used to enhance detection of CIN2-3 in cases where suspicion is high. To evaluate the use of p16INK4a staining in cases of HSIL which were not confirmed on initial biopsy, two pathologists rereviewed Pap and hematoxylin and eosin preparations from all such cases seen within the preceding 3 years. Immunohistochemical study for p16INK4a was performed and graded on representative sections. The results were tabulated and analyzed. Of the identified 596 HSIL Pap cases, 82% had HSIL on initial cervical specimens. Table 1 shows the 56 cases included in the study with graded and stratified p16INK4a results. On review of the p16INK4a slides, only 2 cases could be upgraded to HSIL/CIN2-3 from the original diagnosis. p16INK4a 2-3+ was expressed more frequently in cases initially interpreted on Pap as low-grade cervical lesion as compared with benign (24 of 35 cases). In the younger than 24-yr-old group p16 2-3+ reactivity was more frequent in benign and low-grade cervical lesion/CIN1 groups (benign: 3 of 5 cases, and CIN1: 6 of 8), and p16 negative reactivity was not seen. p16INK4a was graded 0-1+ more frequently in specimens interpreted as benign in the older than 25 yr olds (10 of 16 cases). The study suggests some diagnostic benefit from the use of p16INK4a immunohistochemical study on cervical specimens from women with a HSIL Pap test without HSIL/CIN2-3 on original hematoxylin and eosin review.
在巴氏试验诊断为高级别鳞状上皮内病变（HSIL）后进行的组织活检，有时无法证实相应的高级别宫颈上皮内瘤变（CIN 2 - 3）的存在，这导致在如何最佳管理患者方面产生困惑。研究表明，即使初始活检未能检测到CIN 2 - 3，这些患者未来检测到CIN 2 - 3的风险仍然较高。还表明，p16INK4a免疫组化染色可可靠地用作宫颈样本中高危人乳头瘤病毒感染的替代标志物，并且在怀疑程度较高的情况下可用于提高CIN2 - 3的检测率。为了评估在初始活检未证实的HSIL病例中p16INK4a染色的应用，两名病理学家重新审查了前3年内所见的所有此类病例的巴氏涂片和苏木精 - 伊红切片。对p16INK4a进行免疫组化研究，并在代表性切片上进行分级。结果进行列表和分析。在确定的596例HSIL巴氏涂片病例中，82%在初始宫颈标本中为HSIL。表1显示了纳入研究的56例具有分级和分层p16INK4a结果的病例。在审查p16INK4a玻片时，只有2例可从原始诊断升级为HSIL/CIN2 - 3。与良性病例相比（35例中的24例），p16INK4a 2 - 3+在最初在巴氏涂片上解释为低级别宫颈病变的病例中表达更频繁。在24岁以下的年龄组中，p16 2 - 3+反应性在良性和低级别宫颈病变/CIN1组中更频繁（良性：5例中的3例，CIN1：8例中的6例），且未见p16阴性反应性。在25岁以上被解释为良性的标本中，p16INK4a分级为0 - 1+更频繁（16例中的10例）。该研究表明，对巴氏试验为HSIL但原始苏木精 - 伊红检查无HSIL/CIN2 - 3的女性宫颈标本进行p16INK4a免疫组化研究具有一定的诊断益处。
