Department of Anatomical Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Department of Laboratory Medicine & Pathology, Faculty of Medicine & Dentistry, University of Alberta, Alberta, Canada.
Mod Pathol. 2023 Dec;36(12):100348. doi: 10.1016/j.modpat.2023.100348. Epub 2023 Oct 19.
p53 immunohistochemistry (IHC) has recently been shown to be a clinically useful marker for predicting risk of progression to invasive squamous cell carcinoma in oral epithelial dysplasia (OED). The literature supports the use of p53 IHC as a marker to identify TP53 mutation in in situ and invasive vulvar lesions and as a surrogate marker for high-risk human papillomavirus (HPV) infection, but there is little documentation for similar use in OED. The purpose of this study was to determine whether p53 IHC is a reliable surrogate marker for detecting both TP53 mutation and high-risk HPV infection in OED. We studied 57 cases of OED (11 mild, 18 moderate, and 28 severe), and all were stained for p16 and p53 IHC. High-risk HPV RNA in situ hybridization (ISH) was performed in selected cases (all p16-positive cases and all OED showing abundant apoptotic cells and karyorrhectic cells; N = 27). Targeted next-generation sequencing (NGS) was performed in 33 p16-negative cases and all high-risk HPV RNA ISH-negative cases (N = 36). We identified 21 cases with p53 basal sparing patterns (mid-epithelial and markedly reduced [null-like]), 14 cases with p53 wild-type patterns (scattered basal and patchy basal/parabasal), and 22 cases with p53 abnormal patterns (18 overexpression, 3 null, and 1 novel cytoplasmic pattern). Among cases with p53 basal sparing patterns, 20 were positive for p16 (20/21, 95%), and all were positive for high-risk HPV RNA ISH (21/21, 100%). The 36 sequenced cases had IHC patterns concordant with TP53 mutation status in 92% (33/36) of lesions. This study demonstrates that p53 IHC expression patterns are sensitive and specific for detection of both high-risk HPV infection and TP53 mutation. Coupled with selective p16 IHC testing, this IHC panel can accurately subclassify OED into HPV-associated, p53 wild-type (conventional), and p53 abnormal OED.
p53 免疫组化（IHC）最近被证明是一种预测口腔上皮异型增生（OED）进展为浸润性鳞状细胞癌风险的临床有用标志物。文献支持将 p53 IHC 用作原位和浸润性外阴病变中 TP53 突变的标志物，以及高危人乳头瘤病毒（HPV）感染的替代标志物，但在 OED 中类似用途的文献记录较少。本研究旨在确定 p53 IHC 是否是一种可靠的替代标志物，可用于检测 OED 中的 TP53 突变和高危 HPV 感染。我们研究了 57 例 OED（11 例轻度、18 例中度和 28 例重度），所有病例均进行了 p16 和 p53 IHC 染色。在选定的病例中进行了高危 HPV RNA 原位杂交（ISH）（所有 p16 阳性病例和所有显示大量凋亡细胞和核溶解细胞的 OED；N=27）。在 33 例 p16 阴性病例和所有高危 HPV RNA ISH 阴性病例中进行了靶向下一代测序（NGS）（N=36）。我们鉴定了 21 例具有 p53 基底保留模式（上皮中部和明显减少[类似空泡]）、14 例具有 p53 野生型模式（散在基底和斑块状基底/副基底）和 22 例具有 p53 异常模式（18 例过表达、3 例空泡和 1 例新的细胞质模式）。在具有 p53 基底保留模式的病例中，20 例 p16 阳性（20/21，95%），所有病例高危 HPV RNA ISH 阳性（21/21，100%）。在 36 例测序病例中，92%（33/36）的病变 IHC 模式与 TP53 突变状态一致。本研究表明，p53 IHC 表达模式对检测高危 HPV 感染和 TP53 突变具有敏感性和特异性。结合选择性 p16 IHC 检测，该 IHC 面板可以将 OED 准确地分为 HPV 相关、p53 野生型（常规）和 p53 异常 OED。
