A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Classification of Vulvar Squamous Cell Carcinoma and Precursor Lesions by p16 and p53 Immunohistochemistry: Considerations, Caveats, and an Algorithmic Approach
Tekijät: Yang Hang, Almadani Noorah, Thompson Emily F, Tessier-Cloutier Basile, Chen Julia L, Ho Julie L, Senz Janine, McConechy Melissa K, Chow Christine, Ta Monica, Cheng Angela EL, Karnezis Anthony, Huvila Jutta, McAlpine Jessica N, Gilks Blake, Jamieson Amy, Hoang Lynn N
Kustantaja: Elsevier Science Inc
Julkaisuvuosi: 2023
Journal: Modern Pathology
Tietokannassa oleva lehden nimi: MODERN PATHOLOGY
Lehden akronyymi: MODERN PATHOL
Artikkelin numero: 100145
Vuosikerta: 36
Numero: 6
Sivujen määrä: 12
ISSN: 0893-3952
eISSN: 1530-0285
DOI: https://doi.org/10.1016/j.modpat.2023.100145
Verkko-osoite: https://doi.org/10.1016/j.modpat.2023.100145
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 mutationsdHPV+ category. The use of IHC also led to a revised diagnosesdHSIL 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 algo-rithm that will facilitate the application of p16 and p53 IHC to classify VSCC in pathology practice. Crown Copyright (c) 2023 Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology. All rights reserved.