Pathology and Laboratory Medicine, University of British Columbia and Vancouver General Hospital, British Columbia, Canada.
Department of Pathology, Ministry of the National Guard - Health Affairs, and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Mod Pathol. 2023 Jun;36(6):100145. doi: 10.1016/j.modpat.2023.100145. Epub 2023 Feb 22.
There is emerging evidence that vulvar squamous cell carcinoma (VSCC) can be prognostically subclassified into 3 groups based on human papillomavirus (HPV) and p53 status: HPV-associated (HPV+), HPV-independent/p53 wild-type (HPV-/p53wt), or HPV-independent/p53 abnormal (HPV-/p53abn). Our goal was to assess the feasibility of separating VSCC and its precursors into these 3 groups using p16 and p53 immunohistochemistry (IHC). A tissue microarray containing 225 VSCC, 43 usual vulvar intraepithelial neoplasia (uVIN/HSIL), 10 verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN), and 34 differentiated VIN (dVIN), was stained for p16 and p53. Noncomplementary p16 and p53 patterns were resolved by repeating p53 IHC and HPV RNA in situ hybridization (ISH) on whole sections, and sequencing for TP53. Of 82 p16-positive VSCC, 73 (89%) had complementary p16 and p53 patterns and were classified into the HPV+ group, 4 (4.9%) had wild-type p53 staining, positive HPV ISH and were classified into the HPV+ group, whereas 5 (6.1%) had p53 abnormal IHC patterns (1 null, 4 overexpression), negativity for HPV ISH, and harbored TP53 mutations (1 splice site, 4 missense); they were classified as HPV-/p53abn. Of 143 p16-negative VSCC, 142 (99.3%) had complementary p53 and p16 patterns: 115 (80.4%) HPV-/p53abn and 27 (18.9%) HPV-/p53wt. One had a basal-sparing p53 pattern, positivity for HPV ISH and was negative for TP53 mutations-HPV+ category. The use of IHC also led to revised diagnoses-HSIL to dVIN (3/43), dVIN to vaVIN (8/34), and dVIN to HSIL (3/34). Overall, 215/225 VSCC (95.6%) could be easily classifiable into 3 groups with p16 and p53 IHC. We identified several caveats, with the major caveat being that "double-positive" p16/p53 should be classified as HPV-/p53abn. We propose an algorithm that will facilitate the application of p16 and p53 IHC to classify VSCC in pathology practice.
越来越多的证据表明，外阴鳞状细胞癌（VSCC）可以根据人类乳头瘤病毒（HPV）和 p53 状态分为 3 组：HPV 相关（HPV+）、HPV 非相关/p53 野生型（HPV-/p53wt）或 HPV 非相关/p53 异常（HPV-/p53abn）。我们的目标是使用 p16 和 p53 免疫组化（IHC）来评估将 VSCC 及其前体分为这 3 组的可行性。一个包含 225 例 VSCC、43 例普通外阴上皮内瘤变（uVIN/HSIL）、10 例疣状棘层松解性外阴上皮内瘤变（vaVIN）和 34 例分化型外阴上皮内瘤变（dVIN）的组织微阵列，对 p16 和 p53 进行了染色。非互补的 p16 和 p53 模式通过重复整个切片的 p53 IHC 和 HPV RNA 原位杂交（ISH）以及对 TP53 进行测序来解决。在 82 例 p16 阳性的 VSCC 中，73 例（89%）具有互补的 p16 和 p53 模式，被归类为 HPV+组，4 例（4.9%）具有野生型 p53 染色、HPV ISH 阳性，被归类为 HPV+组，而 5 例（6.1%）具有 p53 异常 IHC 模式（1 例缺失，4 例过表达）、HPV ISH 阴性和 TP53 突变（1 个剪接位点，4 个错义）；它们被归类为 HPV-/p53abn。在 143 例 p16 阴性的 VSCC 中，142 例（99.3%）具有互补的 p53 和 p16 模式：115 例（80.4%）为 HPV-/p53abn，27 例（18.9%）为 HPV-/p53wt。有 1 例具有基底保留的 p53 模式，HPV ISH 阳性，TP53 突变阴性-HPV+类别。免疫组化的使用还导致了修订后的诊断-HSIL 到 dVIN（3/43），dVIN 到 vaVIN（8/34），dVIN 到 HSIL（3/34）。总体而言，215/225 例 VSCC（95.6%）可以通过 p16 和 p53 IHC 轻松分为 3 组。我们发现了一些注意事项，主要的注意事项是“双阳性”p16/p53 应归类为 HPV-/p53abn。我们提出了一个算法，将有助于 p16 和 p53 IHC 在病理实践中用于分类 VSCC。
