Ko Yen Chen Kevin, Liu Kelly Yi Ping, Chen Esther, Zhu Sarah Yuqi, Poh Catherine F
Department of Pathology, BC Cancer, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Oral Medical Biological Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Oral Medical Biological Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada; Department of Integrative Oncology, BC Cancer, Vancouver, British Columbia, Canada; School of Biomedical Engineering, Faculty of Applied Science and Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Mod Pathol. 2024 Dec;37(12):100613. doi: 10.1016/j.modpat.2024.100613. Epub 2024 Sep 10.
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.
口腔上皮发育异常（OED）的分级具有挑战性，观察者内和观察者间的差异相当大。肿瘤抑制蛋白p53的异常免疫组化染色模式最近被证明可能与OED的进展有关。我们回顾性地确定了2001年至2008年一项纵向研究中招募的203例患者的214份口腔活检样本，这些样本诊断为反应性、非发育异常病变、低级别病变（轻度OED和中度OED）和高级别病变（HGLs；重度OED/原位癌）。组织微阵列由病理学最具代表性的区域构建而成。连续切取三张切片，分别进行苏木精和伊红染色、p53免疫组化染色和p16免疫组化染色。两名对临床结果不知情的病理学家（Y.C.K.K.，C.F.P.）对染色结果进行了评估。使用先前发表的基于模式的方法，将样本分为p53异常OED（n = 46）、p53传统OED（n = 118）和p53人乳头瘤病毒（HPV）OED（HPV相关）（n = 12）。所有p53 HPV OED（HPV相关）病例均在HGLs中发现。相比之下，p53异常OED病例在轻度OED（9.5%）、中度OED（23%）和重度OED/原位癌（51%）中均有观察到。27例反应性或非发育异常病变中均未显示p53染色异常模式。在135例低级别病变中，23例（17.0%；2例轻度OED和21例中度OED）进展为HGL或鳞状细胞癌，其中11例在头3年内出现进展。值得注意的是，这些进展较快的病例中有82%（9/11）显示p53模式异常。生存分析显示，与p53传统OED相比，p53异常OED的无进展概率显著更低（P <.0001），风险比为11.24（95%CI，4.26 - 29.66）。此外，与p53野生型OED相比，p53异常OED的局部无复发生存率更低（P =.03）。该研究支持，具有p53异常模式的OED无论发育异常分级如何，进展和复发风险均较高。
