Leica Biosystems p16单克隆抗体在口咽鳞状细胞癌中的作用分析。

IF 2.4 3区医学 Q2 PATHOLOGY

Diagnostic Pathology Pub Date : 2025-01-24 DOI:10.1186/s13000-025-01601-w

Selvam Thavaraj, Max Robinson, Shubham Dayal, Claire Bowen

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引用次数: 0

摘要

背景：头颈部鳞状细胞癌（HNSCC）是全球癌症死亡的第六大原因，仅在美国，新诊断的口咽鳞状细胞癌（OPSCC）病例到2022年就上升到54,000例。最近，人乳头瘤病毒（HPV）感染在OPSCC患者中比传统上已知的致癌物如烟草或酒精更普遍。HPV 16是最常见的致病HPV毒株，在5-10%的HNSCC患者中发现。HPV 16的E6和E7癌蛋白结合并灭活p53和视网膜母细胞瘤（Rb）肿瘤抑制基因。这导致细胞周期抑制基因p16的异常过度表达，导致肿瘤发生。徕卡生物系统公司（LBS）开发了一种p16抗体（6H12克隆），用于免疫组织化学染色定性鉴定福尔马林固定石蜡包埋（FFPE）组织中的p16蛋白。本方法比较研究通过测量170例OPSCC FFPE病例的总体一致性（OA）、平均阳性一致性（APA）和平均阴性一致性（ANA），检验即用型（RTU） LBS p16/LBS RTU p16抗体与罗氏组织诊断（RTD） CINtec p16组织学免疫组化（IHC）检测的一致性率。还评估了两种检测方法的观察者间一致性以及LBS RTU p16与标准HPV分子检测方法（DNA ISH和PCR）的比较。方法：对170例独特的口咽癌病例进行BONDⅲ抗体p16染色定性分析。将该实验与Ventana的RTD E6H4 （CINtec）克隆在Benchmark XT上进行比较。如果Histoscore （H评分）≥140，则认为染色核心p16阳性，如果H评分为阴性。结果：在病理学家中，两种检测的符合率为OA 98.7 - 98.8%, ANA 98.8 -98.9%, APA 98.6%。对于LBS RTU p16，观察者间一致性为OA 98.7%, ANA 98.8%, APA 98.6%；RTD CINtec p16检测的一致性为OA 98.7%, ANA 98.8%, APA 98.6%。病理学家与HPV分子检测、DNA ISH和PCR相比较，LBS p16克隆（LBS RTU p16）的符合率分别为85.8-86.9%和88.6 -88.8%。结论：LBS p16单克隆抗体与CINtec p16 IHC检测在所有终点均表现出较高的一致性，提示LBS RTU p16克隆可用于口咽癌患者p16蛋白检测。

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Performance analysis of Leica Biosystems p16 monoclonal antibody in oropharyngeal squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer death globally, with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) cases rising to 54,000 in the US alone in the year 2022. Recently, human papilloma virus (HPV) infection was more prevalent in OPSCC patients than the traditionally known carcinogens such as tobacco or alcohol. HPV 16 is the most common causative HPV strain, which is found in 5-10% of HNSCC patients. HPV 16's E6 and E7 oncoproteins bind and inactivate p53 and retinoblastoma (Rb) tumor-suppressing genes. This causes aberrant over-expression of the cell cycle inhibitor gene, p16, leading to tumorigenesis. Leica Biosystems (LBS) has developed a p16 antibody (6H12 clone) for qualitatively identifying the p16 protein in formalin-fixed paraffin-embedded (FFPE) tissue by immunohistochemical staining. This method comparison study tested the concordance rates between ready-to-use (RTU) LBS p16/LBS RTU p16 antibody and Roche Tissue Diagnostics (RTD) CINtec p16 Histology immunohistochemical (IHC) assays by measuring overall agreement (OA), average positive agreement (APA), and average negative agreement (ANA) rates in 170 OPSCC FFPE cases. Interobserver agreement of the 2 assays and LBS RTU p16 comparison with the standard HPV molecular assays (DNA ISH and PCR) were also assessed.

Methods: One hundred and seventy (170) unique oropharyngeal cancer cases were stained for qualitative analysis by the LBS p16 antibody on BOND III. This assay was compared to Ventana's RTD E6H4 (CINtec) clone on Benchmark XT. A stained core was considered p16 positive if the Histoscore (H score) was ≥ 140 and negative if H < 140.

Results: Across the pathologists, the agreement rate between the 2 assays ranged from OA, 98.7 - 98.8%, ANA, 98.8 -98.9%, and APA, 98.6%. For LBS RTU p16, the interobserver agreement was OA, 98.7%, ANA, 98.8%, and APA, 98.6%; while for RTD CINtec p16 assay, the concordance was OA, 98.7%, ANA, 98.8% and APA, 98.6%. In comparison to the HPV molecular testing, DNA ISH, and PCR, across pathologists, LBS p16 clone (LBS RTU p16) showed a concordance rate of 85.8-86.9% and 87.6-88.8%, respectively.

Conclusion: LBS p16 monoclonal antibody demonstrated high concordance with CINtec p16 IHC assay across all the endpoints, suggesting a potential use of LBS RTU p16 clone in detecting p16 protein in oropharyngeal cancer cases.

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来源期刊

Diagnostic Pathology 医学-病理学

CiteScore

4.60

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Diagnostic Pathology is an open access, peer-reviewed, online journal that considers research in surgical and clinical pathology, immunology, and biology, with a special focus on cutting-edge approaches in diagnostic pathology and tissue-based therapy. The journal covers all aspects of surgical pathology, including classic diagnostic pathology, prognosis-related diagnosis (tumor stages, prognosis markers, such as MIB-percentage, hormone receptors, etc.), and therapy-related findings. The journal also focuses on the technological aspects of pathology, including molecular biology techniques, morphometry aspects (stereology, DNA analysis, syntactic structure analysis), communication aspects (telecommunication, virtual microscopy, virtual pathology institutions, etc.), and electronic education and quality assurance (for example interactive publication, on-line references with automated updating, etc.).