scholarly journals Molecular Landscape of Vulvar Squamous Cell Carcinoma

2021 ◽  
Vol 22 (13) ◽  
pp. 7069
Author(s):  
Nuria Carreras-Dieguez ◽  
José Guerrero ◽  
Maria Teresa Rodrigo-Calvo ◽  
Inmaculada Ribera-Cortada ◽  
Isabel Trias ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Large Scale ◽  
Small Sample Size ◽  
Small Sample ◽  
Hpv Testing ◽  
Cancer Genes ◽  
Vulvar Squamous Cell Carcinoma ◽  
Molecular Landscape

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with dual pathogenesis, Human papillomavirus (HPV)-associated and HPV-independent, with a poorly explored molecular landscape. We aimed to summarize the findings of the series analyzing molecular hallmarks of this neoplasm. In January 2021, we conducted a comprehensive literature search using Pubmed Medline and Scopus to identify publications focused on genomic profiling of VSCC. Observational studies, including both prospective and retrospective designs, evaluating molecular alterations in VSCC were deemed eligible. A total of 14 studies analyzing 749 VSCC were identified. The study series were heterogeneous in HPV testing and sequencing strategies, included small sets of tumors and cancer genes, and commonly lacked survival analysis. Only one extensive targeted next-generation sequencing-based study comprised a large cohort of 280 VSCC. The mutated genes, their number, and frequencies were highly variable between the series. Overall, TP53 and CDKN2A, followed by PIK3CA, HRAS, and PTEN, were the most frequently studied and mutated genes. Mutations involved in the PI3K/AKT/mTOR pathway, including TP53, HRAS, KRAS, and PIK3CA, have been consistently reported across the studies. However, the role of individual mutations or pathways in the development of VSCC remains unclear. In conclusion, heterogeneity and the small sample size of available molecular series contribute to a limited view of the molecular landscape of VSCC. Large-scale genome- or exome-wide studies with robust HPV testing are necessary to improve the molecular characterization of VSCC.

SOX2 Expression in Gastrointestinal Cancers of Iranian Patients

2015 ◽  
Vol 30 (3) ◽  
pp. 315-320 ◽  
Author(s):  
Fatemeh B Rassouli ◽  
Maryam M Matin ◽  
Ahmad Reza Bahrami ◽  
Kamran Ghaffarzadegan ◽  
Sajjad Sisakhtnezhad ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Small Sample Size ◽  
Treatment Options ◽  
Small Sample ◽  
Sox2 Expression ◽  
Qrt Pcr ◽  
Significant Difference ◽  
Iranian Patients

Purpose Gastrointestinal (GI) malignancies are among the 5 most common cancers in Iran, and their high associated mortality rates are attributable to late diagnosis and poor treatment options. SOX2, a transcription factor necessary for maintenance and induction of pluripotency and self-renewal, has been identified as a lineage-survival oncogene in several cancers. In the present study, we examined SOX2 expression in esophageal squamous cell carcinoma (ESCC), gastric adenocarcinoma and colon squamous cell carcinoma (SCC), as well as normal GI tissues, in Iranian patients. Methods To elucidate the role of SOX2 in GI carcinogenesis, formalin-fixed tissues were analyzed using immunohistochemistry (IHC), while frozen ESCC samples were studied by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results IHC studies indicated presence of SOX2+ cells in a subset of cancerous and normal tissues of stomach and colon, while no significant difference was observed between groups, and no correlation was found between SOX2 expression and tumors grades. Nevertheless, studying ESCC samples with IHC and qRT-PCR revealed overexpression of SOX2 in comparison with normal adjacent tissues. Conclusions The present results are in line with other studies and indicate SOX2 up-regulation in ESCC; however, due to our small sample size and contradictory reports, more research is needed to determine the importance of SOX2 in GI cancers.

scholarly journals Assessing the accuracy of computed tomography in detecting bony invasion and thickness of squamous cell carcinoma of the scalp

2021 ◽  
pp. 197140092110177
Author(s):  
Conor T Boylan ◽  
Michaela S Gaston ◽  
Puja Merwaha ◽  
Kurdow Nader ◽  
Sukhbir Rayatt
Keyword(s):  
Computed Tomography ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Predictive Value ◽  
Small Sample Size ◽  
Small Sample ◽  
Fisher Exact Test ◽  
Temporal Region ◽  
Bony Involvement

Objectives The aim of this study was to ascertain the accuracy of computed tomography (CT) in assessing the presence of bony involvement and thickness of squamous cell carcinoma (SCC) of the scalp. Methods A single-centre retrospective chart review was carried out. Inclusion criteria were scalp SCC, CT between January 2008 and 2018, and the availability of a reference test. Reference tests were either histology, surgical notes or clinical notes. Tabular assessment of accuracy was performed and Student’s t-test, Mann–Whitney U test and Fisher exact test were used in univariable analysis. Accuracy of thickness measurement was calculated using the limits of agreement method, and linear regression was used to examine trend. Results Thirty-nine patients were included. Most patients were male (74.4%), white (97.4%), not immunosuppressed (66.6%) and had poorly differentiated tumours (33.3%). The most common tumour sites were the vertex (28.2%) and temporal region (23.1%). Sensitivity of CT in detecting presence or absence of bony invasion of scalp SCC was 76.9% (95% CI 46.2–94.9%) and specificity was 96.2% (95% CI 80.4-99.9%). Overall accuracy was 89.7% (95% CI 75.8–97.1%), positive predictive value was 90.1% (95% CI 58.7–99.8%) and negative predictive value was 89.3% (95% CI 71.8–97.7%). No significant differences were found comparing patients with an accurate or inaccurate CT scan. Thickness on CT was found to be consistent with histological thickness at the 95% confidence level. Conclusions CT is accurate at assessing the presence of bony involvement and thickness of scalp SCC. This study was limited somewhat by small sample size.

scholarly journals Vulvar Squamous Cell Carcinoma: Comprehensive Genomic Profiling of HPV+ Versus HPV– Forms Reveals Distinct Sets of Potentially Actionable Molecular Targets

2020 ◽  
pp. 647-661
Author(s):  
Erik A. Williams ◽  
Adrienne J. Werth ◽  
Radwa Sharaf ◽  
Meagan Montesion ◽  
Ethan S. Sokol ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Large Scale ◽  
De Novo ◽  
Vulvar Squamous Cell Carcinoma ◽  
Hybridization Capture ◽  
Ccnd1 Amplification ◽  
Comprehensive Genomic Profiling

PURPOSE Vulvar squamous cell carcinoma (vSCC) encompasses two predominant variants: one associated with detectable high-risk strains of human papillomavirus (hrHPV) and a second form often occurring in the context of chronic dermatitis in postmenopausal women. Genomic assessment of a large-scale cohort of patients with aggressive vSCC may identify distinct mutational signatures. MATERIALS AND METHODS Tumor samples from a total of 280 patients with vSCC underwent hybridization capture with analysis of up to 406 cancer-related genes. Human papillomavirus (HPV) sequences were detected by de novo assembly of nonhuman sequencing reads and aligned to the RefSeq database. Immunohistochemistry for programmed death-ligand 1 (PD-L1) was assessed. RESULTS One hundred two of 280 vSCCs (36%) contained hrHPV sequences, predominantly HPV 16 (88%). The HPV-positive (HPV+) group was significantly younger (median age, 59 v 64 years; P = .001). Compared with HPV-negative (HPV–) vSCCs, HPV+ tumors showed more frequent pathogenic alterations in PIK3CA (31% v 16%; P = .004), PTEN (14% v 2%; P < .0001), EP300 (14% v 1%; P < .0001), STK11 (14% v 1%; P < .0001), AR (5% v 0%; P = .006), and FBXW7 (10% v 3%; P = .03). In contrast, HPV– vSCCs showed more alterations in TP53 (83% v 6%; P < .0001), TERTp (71% v 9%; P < .0001), CDKN2A (55% v 2%; P < .0001), CCND1 amplification (22% v 2%; P < .0001), FAT1 (25% v 4%; P < .0001), NOTCH1 (19% v 6%; P = .002), and EGFR amplification (11% v 0%; P < .0001), as well as a higher rate of 9p24.1 ( PDL1/PDL2) amplification (5% v 1%) and PD-L1 immunohistochemistry high-positive tumor staining (33% v 9%; P = .04). CONCLUSION Comprehensive molecular profiles of vSCC vary considerably with hrHPV status and may inform patient selection into clinical trials. Sixty-one percent of HPV+ vSCCs had a pathogenic alteration in the PI3K/mTOR pathway, whereas HPV– vSCCs showed alterations in TP53, TERTp, CDKN2A, CCND1, and EGFR, and biomarkers associated with responsiveness to immunotherapy.

scholarly journals Pan-ERBB kinase inhibition augments CDK4/6 inhibitor efficacy in oesophageal squamous cell carcinoma

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323276
Author(s):  
Jin Zhou ◽  
Zhong Wu ◽  
Zhouwei Zhang ◽  
Louisa Goss ◽  
James McFarland ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Large Scale ◽  
Cell Cancer ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Squamous Cancer ◽  
Striking Success

ObjectiveOesophageal squamous cell carcinoma (OSCC), like other squamous carcinomas, harbour highly recurrent cell cycle pathway alterations, especially hyperactivation of the CCND1/CDK4/6 axis, raising the potential for use of existing CDK4/6 inhibitors in these cancers. Although CDK4/6 inhibition has shown striking success when combined with endocrine therapy in oestrogen receptor positive breast cancer, CDK4/6 inhibitor palbociclib monotherapy has not revealed evidence of efficacy to date in OSCC clinical studies. Herein, we sought to elucidate the identification of key dependencies in OSCC as a foundation for the selection of targets whose blockade could be combined with CDK4/6 inhibition.DesignWe combined large-scale genomic dependency and pharmaceutical screening datasets with preclinical cell line models, to identified potential combination therapies in squamous cell cancer.ResultsWe identified sensitivity to inhibitors to the ERBB family of receptor kinases, results clearly extending beyond the previously described minority of tumours with EGFR amplification/dependence, specifically finding a subset of OSCCs with dual dependence on ERBB3 and ERBB2. Subsequently. we demonstrated marked efficacy of combined pan-ERBB and CDK4/6 inhibition in vitro and in vivo. Furthermore, we demonstrated that squamous lineage transcription factor KLF5 facilitated activation of ERBBs in OSCC.ConclusionThese results provide clear rationale for development of combined ERBB and CDK4/6 inhibition in these cancers and raises the potential for KLF5 expression as a candidate biomarker to guide the use of these agents. These data suggested that by combining existing Food and Drug Administration (FDA)-approved agents, we have the capacity to improve therapy for OSCC and other squamous cancer.

scholarly journals Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Cancers ◽  
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.

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

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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