Comparison of p53 immunohistochemical staining in differentiated vulvar intraepithelial neoplasia (dVIN) with that in inflammatory dermatoses and benign squamous lesions in the vulva

Abstract

Aims Differentiated vulvar intraepithelial neoplasia (dVIN), the precursor lesion to human papillomavirus‐independent vulvar squamous cell carcinoma (VSCC), can be difficult to distinguish from vulvar inflammatory dermatoses. Our goal was to determine if p53 could be a useful biomarker for dVIN, by characterizing p53 percentage, intensity and patterns of staining in dVIN and its histological mimics. Methods and results We studied p53 immunohistochemical staining patterns in 16 dVIN cases and 46 vulvar non‐neoplastic squamous lesions [12 lichen sclerosus (LS); seven lichen simplex chronicus; three lichen planus (LP); six psoriasis; 13 spongiotic dermatitis (SPO); and five candidiasis]. dVIN cases were adjacent to a p16‐negative invasive VSCC in resection specimens. All dVIN cases showed null‐type or moderate to strong uniform p53 staining in >70% of basal cells, with moderate to strong continuous parabasal staining extending to two‐thirds of the epidermis. This was in contrast to weak or weak to moderate patchy p53 staining in the majority of other lesions. Moderate to strong and increased basal p53 staining (≥70%) was also observed in a subset of LS cases (5/12, 42%), LP cases (1/3, 33%), and SPO cases (36%, 4/11); however, in all categories, this was limited to the basal layer, and any staining in the parabasal layers was patchy. Conclusion Strong and uniform p53 staining of basal cells, extending into the parabasal layers, and a complete absence of staining (null type) is useful in distinguishing dVIN from other mimics in the vulva. p53 staining of lesser intensity or quantity, particularly basal overexpression only, overlaps with that in vulvar inflammatory lesions.

p53 Immunohistochemical Patterns in HPV-Independent Squamous Cell Carcinomas of the Vulva and the Associated Skin Lesions: A Study of 779 Cases

“…On the other hand, the two cases with cytoplasmic staining were identified in VSCC with HSIL-like lesion and dVIN. Contrarily, other recent series only identified this pattern in a few VSCC without skin [19] or did not identify it in any of the cases [17].…”

“…The most recent evidence has shown clear prognostic differences based on TP53 mutated or wild-type status in VSCC [16]. p53 IHC has been used as an adjunct in the identification and classification of HPV-independent VSCC and its precursors [17]. However, the criteria of p53 IHC evaluation have remained poorly defined over the last decades.…”

Histological interpretation of differentiated vulvar intraepithelial neoplasia (dVIN) remains challenging—observations from a bi-national ring-study

“…p53-wild-type pattern, i.e., scattered, heterogeneous, basal/para-basal expression, is primarily seen in nondysplastic lesions. However, this pattern has been also occasionally observed in dVIN [15,[20][21][22][23]. Hence, a p53-wild-type pattern does not preclude a histological diagnosis of dVIN.…”

Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)

“…Block-type p16-expression is a reliable surrogate of high-risk HPV-infection, and helps discriminate HSIL from dVIN [40,41]. In addition, mutant pat-terns of p53-expression, i.e., basal and/or parabasal over-expression, or complete absence of expression, can help distinguish dVIN from non-dysplastic lesions [42,43]. Furthermore, the mid-epithelial wild-type p53-expression, which is considered characteristic of HSIL (seen in 96% of HSIL in the current study), can also help discriminate HSIL from dVIN [44].…”

“…However, similarly to most IHC-markers, p53 is not without limitations. Increased p53expression may not only result from the mutated protein, but also from the accumulation of the wild-type protein in response to DNA-damage in inflammatory conditions [42,45]. Therefore, increased p53-expression may be observed in non-dysplastic lesions as well [45].…”