Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
J Clin Pathol. 2010 Nov;63(11):972-7. doi: 10.1136/jcp.2010.078634. Epub 2010 Oct 5.
Histomorphological grading of cervical intraepithelial neoplasia (CIN) is crucial for clinical management. CIN grading is however subjective and affected by substantial rates of discordance among pathologists, which may lead to overtreatment. To minimise this problem, a histology review of CIN lesions by a consensus panel of pathologists is often used. Diffuse strong p16(INK4a) immunostaining has been proposed to aid the identification of true high-grade cervical lesions (ie, CIN2/3).
To assess the value of additional interpretation of p16(INK4a) immunostains for making a more reproducible diagnosis of CIN2/3 lesions.
The authors used a series of 406 biopsies of cervical lesions, with known HPV status, stained for both H&E- and p16(INK4a). First, in a randomly selected set of 49 biopsies, we examined the effect of additional interpretation of p16(INK4a) immunostained slides, on the agreement of CIN diagnosis among three pathologists. Second, the full series of samples was used to assess the accuracy of p16(INK4a)-supported lesion grading by a single pathologist, by evaluating the degree of diagnostic agreement with the consensus diagnosis of expert pathologists based on H&E-stained sections only.
The study shows that the interobserver agreement between three pathologists for the routine H&E-based diagnosis ranged from fair (weighted kappa 0.44 (95% CI 0.19 to 0.64)) to moderate (weighted kappa 0.66 (95% CI 0.47 to 0.79)). The concordance increased substantially for p16(INK4a)-supported grading (mean weighted kappa 0.80 (95% CI 0.66 to 0.89)). Furthermore, an almost perfect agreement was found between the p16(INK4a)-supported diagnosis of a single pathologist and the consensus diagnosis of an expert pathology panel (kappa 0.88 (95% CI 0.85 to 0.89)).
These data demonstrate that additive use of p16(INK4a) immunohistochemistry significantly improves the accuracy of grading CIN lesions by a single pathologist, equalling an expert consensus diagnosis. Hence, the authors advocate the combined use of p16(INK4a)-stained slides and conventional H&E sections in routine histopathology to improve accuracy of diagnosis.
宫颈上皮内瘤变（CIN）的组织形态学分级对于临床管理至关重要。然而，CIN 分级具有主观性，并且在病理学家之间存在大量不一致的情况，这可能导致过度治疗。为了最大程度地减少这个问题，通常会由病理学家共识小组对 CIN 病变进行组织学复查。弥漫性强 p16（INK4a）免疫染色已被提议用于辅助识别真正的高级别宫颈病变（即 CIN2/3）。
评估额外解读 p16（INK4a）免疫染色在更准确地诊断 CIN2/3 病变方面的价值。
作者使用了一系列已知 HPV 状态的 406 份宫颈病变活检样本，这些样本均同时进行了 H&E 和 p16（INK4a）染色。首先，在随机选择的 49 份活检样本中，我们研究了额外解读 p16（INK4a）免疫染色切片对三位病理学家 CIN 诊断一致性的影响。其次，使用完整的样本系列评估了一位病理学家基于 p16（INK4a）支持的病变分级的准确性，方法是评估与仅基于 H&E 染色切片的专家病理学家共识诊断的诊断一致性程度。
研究表明，三位病理学家基于常规 H&E 诊断的观察者间一致性范围从一般（加权 κ 值 0.44（95%CI 0.19 至 0.64））到中度（加权 κ 值 0.66（95%CI 0.47 至 0.79））。通过 p16（INK4a）支持的分级，一致性显著增加（平均加权 κ 值 0.80（95%CI 0.66 至 0.89））。此外，一位病理学家基于 p16（INK4a）的诊断与专家病理小组的共识诊断之间几乎达到完美一致（κ 值 0.88（95%CI 0.85 至 0.89））。
这些数据表明，附加使用 p16（INK4a）免疫组化可显著提高单个病理学家分级 CIN 病变的准确性，与专家共识诊断相当。因此，作者主张在常规组织病理学中联合使用 p16（INK4a）染色切片和常规 H&E 切片以提高诊断准确性。
