徕卡生物系统公司p16单克隆抗体在口咽鳞状细胞癌中的性能分析
Performance analysis of Leica Biosystems p16 monoclonal antibody in oropharyngeal squamous cell carcinoma.
作者信息
Thavaraj Selvam, Robinson Max, Dayal Shubham, Bowen Claire
机构信息
Head and Neck Pathology, Centre for Clinical, Oral & Translational Science, Faculty of Dentistry, King's College London Strand, Guy's Campus, London, SE1 9RT, UK.
Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, 50603, Malaysia.
出版信息
Diagn Pathol. 2025 Jan 24;20(1):9. doi: 10.1186/s13000-025-01601-w.
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.
背景
头颈部鳞状细胞癌（HNSCC）是全球第六大癌症死亡原因，仅在美国，2022年新诊断的口咽鳞状细胞癌（OPSCC）病例就增至54,000例。最近，人乳头瘤病毒（HPV）感染在OPSCC患者中比烟草或酒精等传统已知致癌物更为普遍。HPV 16是最常见的致病性HPV毒株，在5%-10%的HNSCC患者中可检测到。HPV 16的E6和E7癌蛋白会结合并使p53和视网膜母细胞瘤（Rb）肿瘤抑制基因失活。这会导致细胞周期抑制基因p16异常过度表达，从而引发肿瘤形成。徕卡生物系统公司（LBS）开发了一种p16抗体（6H12克隆），用于通过免疫组织化学染色在福尔马林固定石蜡包埋（FFPE）组织中定性鉴定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）率，测试了即用型（RTU）LBS p16/LBS RTU p16抗体与罗氏组织诊断（RTD）CINtec p16组织学免疫组织化学（IHC）检测之间的一致性率。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原位杂交和PCR）的比较情况。
方法
170例独特的口咽癌病例在BOND III上用LBS p16抗体进行染色以进行定性分析。该检测方法与Benchmark XT上的Ventana的RTD E6H4（CINtec）克隆进行比较。如果组织学评分（H评分）≥140，则染色核心被认为p16阳性；如果H<140，则为阴性。
结果
在病理学家中，两种检测方法之间的一致性率范围为：OA为98.7%-98.8%，ANA为98.8%-98.9%，APA为98.6%。对于LBS RTU p16，观察者间一致性为：OA为98.7%，ANA为98.8%，APA为98.6%；而对于RTD CINtec p16检测，一致性为：OA为98.7%，ANA为98.8%，APA为98.6%。与HPV分子检测、DNA原位杂交和PCR相比，在病理学家中，LBS p16克隆（LBS RTU p16）的一致性率分别为85.8%-86.9%和87.6%-88.8%。
结论
LBS p16单克隆抗体在所有终点指标上与CINtec p16 IHC检测显示出高度一致性，表明LBS RTU p16克隆在检测口咽癌病例中的p16蛋白方面具有潜在用途。
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