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

Abstract

Human papillomavirus (HPV)-independent vulvar squamous cell carcinomas (VSCC) and its precursors frequently harbour TP53 mutations. Recently, six p53 immunohistochemical (IHC) patterns have been defined, which have shown strong correlation with TP53 mutation status. However, few studies have applied this new six-pattern framework and none of them exhaustively compared p53 IHC positivity and patterns between invasive VSCC and adjacent skin lesion. We performed p53 IHC in a series of 779 HPV-independent VSCC with adjacent skin and evaluated the IHC slides following the newly described classification. Some 74.1% invasive VSCC showed abnormal p53 IHC staining. A skin lesion was identified in 450 cases (57.8%), including 254 intraepithelial precursors and 196 inflammatory/reactive lesions. Two hundred and ten of 450 (47%) VSCC with associated skin lesions showed an abnormal p53 IHC stain, with an identical staining pattern between the VSCC and the adjacent skin lesion in 80% of the cases. A total of 144/450 (32%) VSCC showed wild-type p53 IHC both in the invasive VSCC and adjacent skin lesion. Finally, 96/450 (21%) VSCC showed p53 IHC abnormal staining in the invasive VSCC but a wild-type p53 staining in the skin lesion. Most of the discordant cases (70/96; 73%) showed adjacent inflammatory lesions. In conclusion, the p53 IHC staining and pattern are usually identical in the VSCC and the intraepithelial precursor.

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.…”

“…This is in line with recent literature, which states that 17–42% cases of dVIN can show wild-type p53-expression [ 4 ], and implies that p53-IHC may not effectively inform the diagnosis in every case of dVIN. Furthermore, p53-IHC patterns in VSCC and the adjacent dVIN may not show perfect concordance [ 22 ]. A recent study reported that while dVIN adjacent to p53-wild-type VSCC always shows wild-type p53-expression, dVIN adjacent to p53-mutant VSCC can show wild-type p53-expression in 31.4% of cases [ 22 ].…”

“…Furthermore, p53-IHC patterns in VSCC and the adjacent dVIN may not show perfect concordance [ 22 ]. A recent study reported that while dVIN adjacent to p53-wild-type VSCC always shows wild-type p53-expression, dVIN adjacent to p53-mutant VSCC can show wild-type p53-expression in 31.4% of cases [ 22 ]. In our study, all of the lesions judged as dVIN by consensus and showing wild-type p53-expression were present adjacent to VSCC.…”

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

“…Mutant patterns of p53-expression are used to support a histological diagnosis of dVIN, as these have been reported to reflect TP53 mutations that characterize dVIN [ 16 , 17 , 18 ]. However, 17–42% of dVIN can show wild-type p53-expression, which is usually observed in non-dysplastic lesions [ 19 , 20 , 21 , 22 ]. Furthermore, recent research has identified a novel putative precursor of HPV-independent VSCC, named differentiated exophytic vulvar intraepithelial lesion (de-VIL) [ 23 ].…”

Topical 5% Imiquimod Sequential to Surgery for HPV-Related Squamous Cell Carcinoma of the Lip

“…Although the oropharyngeal region is usually the most frequently associated with HPV infection, SCC affects other regions, such as the lip and the tongue, have been associated with this viral infection in up to 37% [5]. Interestingly, types 16 and 18 HPV are usually related to this type of tumor, as it happens in cervical cancers [6,7]. HPV 16 accounts for 90% of cases.…”