1071 The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar squamous cell carcinoma

Introduction: The study’s aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14–15.87, p = 0.03) and 2.68 (CI 95% = 1.0–7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.

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Human Papillomavirus-Related Vulvar Squamous Cell Carcinoma

10.32388/1b5vfv ◽

2020 ◽

Author(s):

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Cell Carcinoma ◽

Squamous Cell ◽

Vulvar Squamous Cell Carcinoma

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INTER-OBSERVER AGREEMENT FOR ASSESSING THE DEPTH OF INVASION IN VULVAR SQUAMOUS CELL CARCINOMA

10.26226/morressier.599bdc79d462b80296ca1d2a ◽

2017 ◽

Author(s):

Anne-Floor Pouwer

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Observer Agreement ◽

Depth Of Invasion ◽

Vulvar Squamous Cell Carcinoma

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Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13143580 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3580

Author(s):

Shatavisha Dasgupta ◽

Patricia C. Ewing-Graham ◽

Sigrid M. A. Swagemakers ◽

Thierry P. P. van den Bosch ◽

Peggy N. Atmodimedjo ◽

...

Keyword(s):

Dna Methylation ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Dna Sequences ◽

Cpg Island ◽

Epigenetic Modification ◽

Vulvar Squamous Cell Carcinoma ◽

Differentially Methylated Genes ◽

Methylation Profiling

DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ± 0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.

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Pembrolizumab in vaginal and vulvar squamous cell carcinoma: a case series from a phase II basket trial

Scientific Reports ◽

10.1038/s41598-021-83317-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeffrey A. How ◽

Amir A. Jazaeri ◽

Pamela T. Soliman ◽

Nicole D. Fleming ◽

Jing Gong ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Phase Ii ◽

Squamous Cell ◽

Single Agent ◽

Case Series ◽

Predictive Biomarkers ◽

Vulvar Squamous Cell Carcinoma ◽

Metastatic Setting ◽

Progression Of Disease

AbstractVaginal and vulvar squamous cell carcinoma (SCC) are rare tumors that can be challenging to treat in the recurrent or metastatic setting. We present a case series of patients with vaginal or vulvar SCC who were treated with single-agent pembrolizumab as part of a phase II basket clinical trial to evaluate efficacy and safety. Two cases of recurrent and metastatic vaginal SCC, with multiple prior lines of systemic chemotherapy and radiation, received pembrolizumab. One patient had significant reduction (81%) in target tumor lesions prior to treatment discontinuation at cycle 10 following confirmed progression of disease with new metastatic lesions (stable disease by irRECIST criteria). In contrast, the other patient with vaginal SCC discontinued treatment after cycle 3 due to disease progression. Both patients had PD-L1 positive vaginal tumors and tolerated treatment well. One case of recurrent vulvar SCC with multiple surgical resections and prior progression on systemic carboplatin had a 30% reduction in her target tumor lesions following pembrolizumab treatment with a PD-L1 positive tumor. Treatment was discontinued for grade 3 mucositis after cycle 5. Pembrolizumab may provide some clinical benefit to some patients with vaginal or vulvar SCC and is overall safe to utilize in this population. Future studies are needed to evaluate the efficacy of pembrolizumab in these rare tumor types and to identify predictive biomarkers of response.

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