p53 Abnormal Oral Epithelial Dysplasias are Associated With High Risks of Progression and Local Recurrence—A Retrospective Study in a Longitudinal Cohort

IF 7.1 1区医学 Q1 PATHOLOGY

Modern Pathology Pub Date : 2024-09-10 DOI:10.1016/j.modpat.2024.100613

Yen Chen Kevin Ko , Kelly Yi Ping Liu , Esther Chen , Sarah Yuqi Zhu , Catherine F. Poh

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Abstract

Grading of oral epithelial dysplasia (OED) can be challenging with considerable intraobserver and interobserver variability. Abnormal immunohistochemical staining patterns of the tumor suppressor protein, p53, have been recently shown to be potentially associated with progression in OED. We retrospectively identified 214 oral biopsies from 203 patients recruited in a longitudinal study between 2001 and 2008 with a diagnosis of reactive, nondysplastic lesions, low-grade lesions (mild OED and moderate OED) and high-grade lesions (HGLs; severe OED/carcinoma in situ). Tissue microarrays were constructed from the most representative area of the pathology. Three consecutive sections were sectioned and stained for hematoxylin and eosin, p53 immunohistochemistry, and p16 immunohistochemistry. The staining results were reviewed by 2 pathologists (Y.C.K.K., C.F.P.) blinded to clinical outcome. Samples were categorized into p53 abnormal OED (n = 46), p53 conventional OED (n = 118), and p53 human papillomavirus (HPV) OED (HPV associated) (n = 12) using a previously published pattern-based approach. All cases of p53 HPV OED (HPV associated) were identified in HGLs. In contrast, cases of p53 abnormal OED were observed in mild OED (9.5%), moderate OED (23%), and severe OED/carcinoma in situ (51%). None of the 27 reactive or nondysplastic lesions showed abnormal p53 staining patterns. Among the 135 low-grade lesions, 23 cases (17.0%; 2 mild OEDs and 21 moderate OEDs) progressed to HGL or squamous cell carcinoma, with 11 cases showing progression within the first 3 years. Remarkably, 82% (9/11) of these faster progressors showed abnormal p53 patterns. Survival analysis revealed that p53 abnormal OED had significantly poorer progression-free probability (P < .0001) with hazard ratio of 11.24 (95% CI, 4.26-29.66) compared with p53 conventional OED. Furthermore, p53 abnormal OED had poorer local recurrence–free survival compared with p53 wild-type OED (P = .03). The study supports that OED with p53 abnormal pattern is at high risk for progression and recurrence independent of the dysplasia grade.

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p53异常口腔上皮增生异常与病情恶化和局部复发的高风险有关--一项纵向队列的回顾性研究。

口腔上皮发育不良（OED）的分级具有挑战性，观察者内部和观察者之间的差异很大。最近的研究表明，肿瘤抑制蛋白 p53 的异常免疫组化染色模式可能与 OED 的进展有关。我们回顾性地鉴定了 2001 年至 2008 年间一项纵向研究招募的 203 名患者的 214 份口腔活检样本，诊断为反应性、非增生性病变、低级别病变（LGLs；轻度 OED、中度 OED）和高级别病变（HGLs；重度 OED/原位癌）。组织微阵列（TMA）由最具代表性的病理区域构建而成。对三个连续切片进行切片，并进行苏木精和伊红染色、p53 免疫组化和 p16 免疫组化。染色结果由两名对临床结果保密的病理学家进行审核。采用之前发表的基于模式的方法，将样本分为p53-异常OED（n = 46）、p53-常规OED（n = 118）和p53-HPV（HPV相关）OED（n = 12）。所有p53-HPV（HPV相关）OED病例都是在HGLs中发现的。相比之下，p53异常的OED病例出现在轻度OED（9.5%）、中度OED（23%）和重度OED/原位癌（51%）中。27个反应性或非增生性病变中没有一个显示出异常的p53染色模式。在135例LGL中，23例（17.0%；2例轻度OED和21例中度OED）进展为HGL或鳞癌，其中11例在最初3年内出现进展。值得注意的是，在这些进展较快的病例中，82%（9/11）的病例显示出异常的 p53 模式。生存期分析表明，p53异常的OED的无进展概率明显较低（p

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来源期刊

Modern Pathology 医学-病理学

CiteScore

14.30

自引率

2.70%

发文量

174

审稿时长

18 days

期刊介绍： Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.