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Uveal melanomas (UMs) represent rare malignant tumors associated with grim prognosis for the majority of patients. DAXX (Death Domain-Associated Protein), HJURP (Holliday Junction Recognition Protein) and CENPA (Centromere Protein A) proteins are implicated in epigenetic mechanisms, now in the spotlight of cancer research to better understand the molecular background of tumorigenesis. Herein, we investigated their expression in UM tissues using immunohistochemistry and explored possible correlations with a multitude of clinicopathological and survival parameters. The Cancer Genome Atlas Program (TCGA) was used for the investigation of their mRNA levels in UM cases. Nuclear DAXX expression correlated with an advanced T-stage ( p = 0.004), while cytoplasmic expression marginally with decreased disease-free survival (DFS) ( p = 0.084). HJURP nuclear positivity also correlated with advanced T-status ( p = 0.054), chromosome 3 loss ( p = 0.042) and increased tumor size ( p = 0.03). More importantly, both nuclear and cytoplasmic HJURP immunopositivity correlated with decreased overall survival (OS) ( p = 0.011 and 0.072, respectively) and worse DFS ( p = 0.071 and 0.019, respectively). Lastly, nuclear CENPA overexpression was correlated with presence of irido-corneal angle involvement ( p = 0.015) and loss of chromosome 3 ( p = 0.041). Nuclear and cytoplasmic CENPA immunopositivity associated with decreased OS ( p = 0.028) and DFS ( p = 0.018), respectively. HJURP and CENPA mRNA overexpression exhibited strong association with tumor epithelioid histology and was linked to worse prognosis. Our results show the compounding role of DAXX, HJURP and CENPA in UM carcinogenesis, designating them as potential biomarkers for assessing prognosis and possible targets for novel therapeutic interventions.

Background: Programmed death-ligand 1 (PD-L1) expression in neoplastic and immune cells of the tumor microenvironment determines the efficacy of antitumor immunity, while it can be regulated at the epigenetic level by various factors, including HDACs. In this study, we aim to evaluate the expression patterns of PD-L1 in thymic epithelial tumors (TETs), while we attempt the first correlation analysis between PD-L1 and histone deacetylases (HDACs) expression., Methods: Immunohistochemistry was used to evaluate the expression of PD-L1 in tumor and immune cells of 91 TETs with SP263 and SP142 antibody clones, as well as the expressions of HDCA1, -2, -3, -4, -5, and -6., Results: The PD-L1 tumor proportion score (TPS) was higher, while the immune cell score (IC-score) was lower in the more aggressive TET subtypes and in more advanced Masaoka-Koga stages. A positive correlation between PD-L1 and HDAC-3, -4, and -5 cytoplasmic expression was identified., Conclusions: Higher PD-L1 expression in neoplastic cells and lower PD-L1 expression in immune cells of TETs characterizes more aggressive and advanced neoplasms. Correlations between PD-L1 and HDAC expression unravel the impact of epigenetic regulation on the expression of immune checkpoint molecules in TETs, with possible future applications in combined therapeutic targeting.

Genomic profiling has improved our understanding of the pathogenesis of different cancers and led to the development of several targeted therapies, especially in epithelial tumors. In this review, we focus on the clinical utility of next-generation sequencing (NGS) to inform therapeutics in soft tissue sarcoma (STS). The role of NGS is still controversial in patients with sarcoma, given the low mutational burden and the lack of recurrent targetable alterations in most of the sarcoma histotypes. The clinical impact of genomic profiling in STS has not been investigated prospectively. A limited number of retrospective, mainly single-institution, studies have addressed this issue using various NGS technologies and platforms and a variety of criteria to define a genomic alteration as actionable. Despite the detailed reports on the different gene mutations, fusions, or amplifications that were detected, data on the use and efficacy of targeted treatment are very scarce at present. With the exception of gastrointestinal stromal tumors (GISTs), these targeted therapies are administered either through off-label prescription of an approved drug or enrollment in a matched clinical trial. Based mainly on anecdotal reports, the outcome of targeted therapies in the different STS histotypes is discussed. Prospective studies are warranted to assess whether genomic profiling improves the management of STS patients.

Ovarian cancer (OC) is the leading cause of death from gynecological malignancies. Despite great advances in treatment strategies, therapeutic resistance and the gap between preclinical data and actual clinical efficacy justify the necessity of developing novel models for investigating OC. Organoids represent revolutionary three-dimensional cell culture models, deriving from stem cells and reflecting the primary tissue's biology and pathology. The aim of the current review is to study the current status of mouse- and patient-derived organoids, as well as their potential to model carcinogenesis and perform drug screenings for OC. Herein, we describe the role of organoids in the assessment of high-grade serous OC (HGSOC) cells-of-origin, illustrate their use as promising preclinical OC models and highlight the advantages of organoid technology in terms of disease modelling and drug sensitivity testing.