HPV-independent Precursors Mimicking High-grade Squamous Intraepithelial Lesions (HSIL) of the Vulva

Rakislova, Natalia; Alemany, Laia; Clavero, Omar; Pino, Marta del; Saco, Adela; Marimón, Lorena; Quirós, Beatriz; Lloveras, Belén; Ribera‐Cortada, Inmaculada; Alejo, María; Pawlita, Michael; Quint, Wim; Sanjosé, Sílvia de; Ordï, Jaume

doi:10.1097/pas.0000000000001540

Cited by 24 publications

(60 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have increasingly recognized that accurate diagnosis of dVIN may not be achieved on the basis of histological assessment alone [38][39][40][41]. The spectrum of histological features of dVIN can overlap with that of non-dysplastic lesions, and occasionally, with that of HPV-related HSILs as well [40,41].…”

Section: Discussionmentioning

confidence: 99%

“…The spectrum of histological features of dVIN can overlap with that of non-dysplastic lesions, and occasionally, with that of HPV-related HSILs as well [40,41]. Therefore, to improve diagnostic accuracy, an IHC panel comprising p16 and p53 is being recommended for lesions with a histological suspicion of dVIN [2,4,17,39]. Block-type p16-expression is a reliable surrogate of high-risk HPV-infection, and helps discriminate HSIL from dVIN [40,41].…”

Section: Discussionmentioning

confidence: 99%

“…MIB1: increased expression = increased nuclear expression in the basal and/or parabasal layers; not increased expression = sporadic nuclear expression in basal (minor component) layers and/or parabasal layers (major component) [30,39].…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2021

View full text Add to dashboard Cite

Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC—the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN (n = 56), de-VIL (n = 8), and non-dysplastic vulvar tissues (n = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN (n = 8) and de-VIL (n = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues (p < 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, TP53 mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Several intraepithelial precursors have been described in association with HPV-independent VSCC. They include differentiated vulvar intraepithelial neoplasia (dVIN), the classical precursor of HPV-independent VSCC [3][4][5][6][7][8], but also other new entities that have recently been added to the list of HPV-independent premalignant lesions: HSIL-like lesion [9], also referred to as basaloid dVIN [10], vulvar acanthosis with altered differentiation (VAAD) [11], and the closely related differentiated exophytic vulvar intraepithelial lesion (DEVIL) [12]. Finally, chronic inflammatory skin lesions, such as lichen sclerosus (LS), and other inflammatory/reactive skin lesions, including lichen planus, lichen simplex chronicus, and other lesions, are frequently identified in these patients [13].…”

Section: Introductionmentioning

confidence: 99%

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

Rakislova

Alemany

Clavero

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…HPV-associated tumors have a basaloid or verrucous morphology and represent almost half of all VSCC cases, often occurring in younger women. The HPV-independent subset, on the other hand, tends to occur in older women (50+ years old) and is frequently associated with either chronic inflammatory skin conditions, such as lichen sclerosus, lichen planus, or differentiated vulvar intraepithelial neoplasia (d-VIN) [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis

Ferreira

Almeida

Anjos

et al. 2021

IJMS

View full text Add to dashboard Cite

The role and prognostic value of tetraspanins (TSPANs) in vulvar squamous cell carcinoma (VSCC) remain poorly understood. We sought to primarily determine, at both the molecular and tissue level, the expression profile of the TSPANs CD9, CD63, CD81, and CD82 in archived VSCC samples (n = 117) and further investigate their clinical relevance as prognostic markers. Our studies led us to identify CD63 as the most highly expressed TSPAN, at the gene and protein levels. Multicomparison studies also revealed that the expression of CD9 was associated with tumor size, whereas CD63 upregulation was associated with histological diagnosis and vascular invasion. Moreover, low expression of CD81 and CD82 was associated with worse prognosis. To determine the role of TSPANs in VSCC at the cellular level, we assessed the mRNA levels of CD63 and CD82 in established metastatic (SW962) and non-metastatic (SW954) VSCC human cell lines. CD82 was found to be downregulated in SW962 cells, thus supporting its metastasis suppressor role. However, CD63 was significantly upregulated in both cell lines. Silencing of CD63 by siRNA led to a significant decrease in proliferation of both SW954 and SW962. Furthermore, in SW962 particularly, CD63-siRNA also remarkably inhibited cell migration. Altogether, our data suggest that the differential expression of TSPANs represents an important feature for prognosis of VSCC patients and indicates that CD63 and CD82 are likely potential therapeutic targets in VSCC.

show abstract

HPV-independent Precursors Mimicking High-grade Squamous Intraepithelial Lesions (HSIL) of the Vulva

Cited by 24 publications

References 23 publications

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

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

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

Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis

Contact Info

Product

Resources

About