P14/ARF was evaluated in 68 patients who had a sufficient number of tumor cells. A random forest-based machine-learning algorithm (Boruta) was implemented to identify which variables were associated with p14/ARF expression. The expression of p14/ARF was associated with several clinical and pathological characteristics. Inflammatory cell components (CD3+, CD4+, CD8+ T lymphocytes CD20+ B-lymphocytes CD68+ and CD163+ macrophages) were quantified as percentages of positive cells, distinguishing between intratumoral and peritumoral areas. We evaluated p14/ARF, PD-L1 (tumor proportion score, TPS), and Ki-67 (percentage) by immunohistochemistry. Pathological assessments of histotype, necrosis, inflammation, grading, and mitosis were performed. We aimed to determine whether there is a relationship between p14/ARF expression, tumor morphological features, and the inflammatory tumor microenvironment.ĭiagnostic biopsies from 76 chemo-naive MPMs were evaluated. The exact role of p14/ARF in MPM and overall its correlation with the immune microenvironment is unknown. The gene encodes for two tumor suppressor proteins, p16/INK4A and p14/ARF, frequently lost in MPM tumors. The CDKN2A gene plays a central role in the pathogenesis of malignant pleural mesothelioma (MPM). This orthotopic model with rapid development of MMe without asbestos exposure represents genomic instability and specific molecular targets for therapeutic or preventive interventions to enable preclinical proof of concept for the intervention in an immunocompetent setting. In addition, microsatellite markers were detectable in the plasma of tumor-bearing mice, indicating a potential use for early cancer detection and monitoring the effects of interventions. Moreover, MMe cells showed mixed chromosome and microsatellite instability, supporting the notion that genomic instability is relevant in MMe pathogenesis. These MMe cells were tumorigenic upon intraperitoneal injection. We characterized an orthotopic model using MMe cells derived from Cdkn2a+/− Nf2+/− mice chronically injected with asbestos. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities.
0 kommentar(er)
