UNCOVERING VULVAR CARCINOMA: AN INTEGRATIVE APPROACH [GE]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE86970 | GEO | 2016/09/15
SECONDARY ACCESSION(S): PRJNA343114
REPOSITORIES: GEO
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Project description:Array-based comparative genomic hybridization (array CGH) analyses was used to analyze 17 VSCC samples from untreated patients. The data were validated using quantitative PCR.
2016-09-15 | GSE86969 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-09-15 | GSE68409 | GEO
Project description:UNCOVERING VULVAR CARCINOMA: AN INTEGRATIVE APPROACH
| PRJNA343113 | ENA
Project description:Although oncogynaecological management of bulky vulvar tumors tends to minimally-invasive approaches preceded by neoadjuvant therapies, ultra-radical surgery with curative intent may still have an important role. These procedures remain associated with significant short and long-term complications, imposing the need for novel reconstructive techniques [Brown et al., 2017, Di Donato et al., 2017, Moreno-Palacios et al., 2015, Oonk et al., 2017]. We present a video highlighting the crucial surgical steps of a successful pelvic exenterative procedure followed by perineal reconstruction with a muscle-sparing flap technique. A 72-year woman with history of stage II vulvar epidermoid carcinoma, treated with radical surgery and adjuvant radiotherapy. At two-year follow-up local recurrence was diagnosed, handled with large excisional surgical treatment. Within four years a second local recurrence occurred, with infiltrative and bulky dimensions extending to perianal region and vaginal wall. A multidisciplinary surgical approach with curative intent was performed, involving gynecologists, colorectal and plastic surgeons: radical bilateral vulvectomy with distal colpectomy, abdominoperineal resection with colostomy, perineal reconstruction with deep inferior epigastric perforators (DIEP) flap. No major intraoperative or postoperative complications occurred, and the patient was discharged within two weeks with no readmissions for wound care. At two-year follow up she remains in complete remission of the disease. No flap complications occurred during this period. In highly selected patients with recurrent vulvar cancer previously submitted to multiple surgeries and radiotherapy, pelvic exenterative procedures followed by reconstructive techniques allow free surgical margins minimizing morbidity and pelvic disfiguring surgery. Association of reconstructive techniques to radical vulvo-vaginal surgery can shift the paradigm of oncological treatment approach, improving outcomes and quality-of-life.
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Project description:Chromosomal organization in 3D plays a central role in regulating cell-type specific transcriptional and DNA replication timing programs. Yet it remains unclear to what extent the resulting long-range contacts depend on specific molecular drivers. Here we propose a model that comprehensively assesses the influence on contacts of DNA-binding proteins, cis-regulatory elements and DNA consensus motifs. Using real data, we validate a large number of predictions for long-range contacts involving known architectural proteins and DNA motifs. Our model outperforms existing approaches including enrichment test, random forests and correlation, and it uncovers numerous novel long-range contacts in Drosophila and human. The model uncovers the orientation-dependent specificity for long-range contacts between CTCF motifs in Drosophila, highlighting its conserved property in 3D organization of metazoan genomes. Our model further unravels long-range contacts depending on co-factors recruited to DNA indirectly, as illustrated by the influence of cohesin in stabilizing long-range contacts between CTCF sites. It also reveals asymmetric contacts such as enhancer-promoter contacts that highlight opposite influences of the transcription factors EBF1, EGR1 or MEF2C depending on RNA Polymerase II pausing.
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Project description:The rather rare vulvar cancer is almost always a squamous cell carcinoma that mostly develops from an underlying VIN or HPV infection. In addition, lichen sclerosus et atrophicans, immune deficiency, nicotine abuse or anogenital intraepithelial neoplasias may play a role in the pathogenesis. Surgical therapy aims at an R0 resection in the sense of a complete vulvectomy or a radical local excision with, if necessary, plastic reconstruction. Also, the vulvar field resection with consideration of the compartment model has been discussed. Besides the classic inguinofemoral lymphadenectomy, in selected cases of vulvar cancer sentinel biopsies are performed by experienced surgeons in the larger centres. In contrast, systemic therapy plays only a subordinate role; in isolated cases down-staging by means of neoadjuvant chemotherapy may be useful. However, there is at present no indication for adjuvant chemotherapy. Neoadjuvant radiochemotherapy is also not to be recommended on account of its unfavourable ratio of efficacy to side effects. On the other hand adjuvant radiotherapy is indicated in cases of positive inguinal lymph nodes. According to the current data the indication should be made generously in such cases.
| S-EPMC4024610 | biostudies-other
Project description: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). 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. 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. 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.
| S-EPMC8699435 | biostudies-literature
Project description:Vulvar squamous cell cancer (VSC) accounts for 90% of vulvar cancers. Next-generation sequencing studies of VSC imply human papillomavirus (HPV) and p53 status play separate roles in carcinogenesis and prognosis. We sought to describe the genomic landscape and analyze the immunologic profiles of VSC with respect to HPV and p53 status. A total of 443 VSC tumors underwent tumor profiling. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor samples. PD-L1, microsatellite instability were tested by fragment analysis, IHC, and next-generation sequencing. Tumor mutational burden-high was defined as >10 mutations per MB. HPV 16/18 positive (HPV+) status was determined using whole exome sequencing on 105 samples. Three cohorts were identified from 105 samples with known HPV: HPV+, HPV-/p53wt, and HPV-/p53mt. Where HPV and p53 status were examined, TP53 mutations were exclusive of HPV+ tumors. In all, 37% of samples were HPV+. Among the 66 HPV- tumors, 52 (78.8%) were HPV-/p53mt and 14 (21.2%) were HPV-/p53wt. The HPV-/p53wt cohort had a higher rate of mutations in the PI3KCA gene (42.9% HPV-/p53wt vs 26.3% HPV+ vs. 5.8% HPV-/p53mt, q =0.028) and alterations in the PI3K/AkT/mTOR pathway (57.1% HPV-/p53wt vs. 34.2% HPV+ vs. 7.7% HPV-/p53mt, q =0.0386) than the other 2 cohorts. Ninety-eight VSC tumors with HPV16/18 information underwent transcriptomic analysis and immune deconvolution method. No differences were observed in immune profiles. The HPV-/p53wt VSC tumors had significantly higher rates of mutations in the PI3KCA gene and alterations in the PI3K/AkT/mTOR pathway, a potential target that merits further investigation in this subgroup.
| S-EPMC10417246 | biostudies-literature
Project description:The ELECHTRA (ELEctroChemoTherapy vulvaR cAncer) project was conceived to collect data on palliative electrochemotherapy (ECT) in vulvar cancer (VC) assessing patients' outcomes (response and survival) and impact on quality of life (QoL). After reporting outcome data in 2019, here, we present the results on QoL. A multicenter prospective observational study was conducted on patients with VC refractory or not amenable to standard therapies undergoing palliative ECT as per clinical practice. The following questionnaires were administered before and after ECT (two and four months later, early and late follow-up): visual analog pain scale (VAS), EuroQol 5-Dimension 5-Level (EQ-5D-L5) and Functional Assessment of Cancer Therapy-Vulva cancer (FACT-V). Analyses were conducted on both the whole study population and by subgroups (clinical response after ECT and site, number and size of lesions). Questionnaires from 55 patients were evaluated. Compared to the baseline (6.1 ± 2.1), the VAS was significantly reduced at early (4.3 ± 2.5) and late follow-up (4.6 ± 2.8) (p < 0.0001). The FACT-V score improved significantly at early (9.6 ± 4.0) (p < 0.0001) and late follow-up (8.9 ± 4.1) (p < 0.0054) as compared to the baseline (7.1 ± 3.6). No EQ-5D-5L statistically significant changes were observed. Subgroup analyses showed worse QoL in patients with stable or progressive disease, posterior site and multiple or larger than 3 cm nodules. This is the first study reporting improved QoL in VC patients after palliative ECT. Based on these results, ECT in VC should be considered an effective option based on the favorable outcomes both in terms of response and QoL.
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Project description:A growing number of studies on gynecological cancers (GCs) have revealed potential gene markers associated either with the pathogenesis and progression of the disease on representing putative targets for therapy and treatment of cervical (CC), endometrial (EC) and vulvar cancer (VC). However, quite a little overlap is found between these data. In this study we combined data from the three GCs integrating gene expression profile analysis. The meta-analysis including our results and data emerge from other available studies on gynecological malignancies and other cancer types, revealed common properties among them including deregulation of cell cycle, immune response, antiviral response and apoptosis.
2015-07-26 | GSE63678 | GEO