Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.
Department of Otorhinolaryngology - Head and Neck Surgery, University of Turku and Turku University Hospital, Turku, Finland.
Head Neck Pathol. 2024 Aug 7;18(1):73. doi: 10.1007/s12105-024-01680-z.
Our aim was to assess the ability of simultaneous immunohistochemical staining (IHC) for p16 and p53 to accurately subclassify head and neck squamous cell carcinomas (HNSCC) as HPV-associated (HPV-A) versus HPV-independent (HPV-I) and compare p53 IHC staining patterns to TP53 mutation status, p16 IHC positivity and HPV status.
We stained 31 HNSCCs for p53 and p16, and performed next-generation sequencing (FoundationOne©CDx) on all cases and HPV in-situ hybridization (ISH) when sufficient tissue was available (n = 23). p53 IHC staining patterns were assessed as wildtype (wt) or abnormal (abn) patterns i.e. overexpression, null or cytoplasmic staining.
In a majority of cases (28/31) interpretation of p16 and p53 IHC was straightforward; 10 were considered HPV-A (p16+/p53wt) and 18 cases were HPV-I (p16-/p53abn). In the remaining three tumours the unusual immunophenotype was resolved by molecular testing, specifically (i) subclonal p16 staining and wild type p53 staining in a tumour positive for HPV and with no TP53 mutation (HPV-A), (ii) negative p16 and wild type p53 staining with a TP53 mutation and negative for HPV (HPV-I), and (iii) equivocally increased p16 staining with mutant pattern p53 expression, negative HPV ISH and with a TP53 mutation (HPV-I).
Performing p16 and p53 IHC staining simultaneously allows classification of most HNSCC as HPV-A (p16 +, p53 wild type (especially basal sparing or null-like HPV associated staining patterns, which were completely specific for HPV-A SCC) or HPV-I (p16 -, p53 mutant pattern expression), with the potential for limiting additional molecular HPV or mutational testing to selected cases only.
我们旨在评估同时进行 p16 和 p53 免疫组织化学染色（IHC）是否能够准确地将头颈部鳞状细胞癌（HNSCC）分为 HPV 相关型（HPV-A）与 HPV 非相关型（HPV-I），并比较 p53 IHC 染色模式与 TP53 突变状态、p16 IHC 阳性和 HPV 状态的关系。
我们对 31 例 HNSCC 进行了 p53 和 p16 的 IHC 染色，并对所有病例进行了下一代测序（FoundationOne©CDx），当组织足够时，对 23 例进行了 HPV 原位杂交（ISH）。p53 IHC 染色模式评估为野生型（wt）或异常（abn）模式，即过表达、缺失或细胞质染色。
在大多数病例（28/31）中，p16 和 p53 IHC 的解释是直接的；10 例被认为是 HPV-A（p16+/p53wt），18 例是 HPV-I（p16-/p53abn）。在其余三例肿瘤中，通过分子检测解决了不寻常的免疫表型，具体为（i）HPV 阳性、无 TP53 突变的肿瘤中存在亚克隆性 p16 染色和野生型 p53 染色（HPV-A），（ii）HPV 阴性、野生型 p53 染色和 TP53 突变的肿瘤（HPV-I），以及（iii）p16 染色增加、p53 表达突变模式、HPV ISH 阴性和 TP53 突变的肿瘤（HPV-I）。
同时进行 p16 和 p53 IHC 染色可将大多数 HNSCC 分为 HPV-A（p16 +，p53 野生型（特别是基底保留或类似缺失的 HPV 相关染色模式，这些模式完全特异于 HPV-A SCC）或 HPV-I（p16 -，p53 突变模式表达），可能只需要对少数病例进行额外的 HPV 或突变分子检测。
