Establishment and Histopathological Study of Patient-derived Xenograft Models and Primary Cell Lines of Epithelioid Malignant Peritoneal Mesothelioma
Background: Malignant peritoneal mesothelioma (MPM) is a rare malignancy with few effective therapies. This study established patient-derived xenograft (PDX) models and primary cell lines to provide a study platform for MPM in vitro and in vivo, and conducted histopathological analysis.Methods: Human MPM surgical specimen was collected to establish PDX models and primary cell lines. Experimental peritoneal cancer index (ePCI) score was used to evaluate gross pathology, and histopathological
... stopathological study was conducted by hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining. Pathological characteristics of the established primary MPM cell lines were analyzed by Swiss-Gimsa and immunofluorescence (IF) staining. The whole-exome sequencing (WES) was performed to identify the mutant genes between models and the patient.Results: MPM PDX models and primary cell lines were successfully established, replicated the pathological features of the patient. ePCI score of the female and male nude mice were 8.80 ± 1.75 and 9.20 ± 1.81 (P = 0.6219), respectively. The HE staining showed that the tumor was epithelioid mesothelioma and invaded multiple organs. IHC staining showed that Calretinin, Cytokeratin 5/6, WT-1 and Ki-67 were all positive. The Swiss-Gimsa and IF staining of primary cell lines were also consistent with the pathological characteristics of mesothelioma. The WES showed that 21 mutant genes were shared between models and the patient, and the genes related to tumorigenesis and development including BAP1, NF2, MTBP, NECTIN2, CDC23, LRPPRC, TRIM25, and DHRS2.Conclusions: PDX models and primary cell lines of MPM were successfully established with the epithelioid mesothelioma identity confirmed by histopathological evidence. Moreover, our study has also illustrated the shared genomic profile between models and the patient, then potentially provided new targets for MPM treatment.