Related Experiment Video
Updated: Jul 27, 2025
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Recurrent Tumor Suppressor Alterations in Primary Pericardial Mesothelioma
Inga-Marie Schaefer1, Adrian Mariño-Enríquez1, Mark M Hammer2
1Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Abstract:
Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be determined. Here, we report the clinicopathologic, immunohistochemical, and molecular genetic findings of 3 pericardial mesotheliomas without pleural involvement. Three cases diagnosed between 2004 and 2022 were included in the study and analyzed by immunohistochemistry and targeted next-generation sequencing (NGS); corresponding nonneoplastic tissue was sequenced in all cases. Two patients were female and 1 was male, aged between 66 and 75 years. Two patients each had prior asbestos exposure and were smokers. Histologic subtypes were epithelioid in 2 cases and biphasic in 1 case. Immunohistochemical staining identified expression of cytokeratin AE1/AE3 and calretinin in all cases, D2-40 in 2 cases, and WT1 in 1 case. Staining for tumor suppressors revealed loss of p16, MTAP, and Merlin (NF2) expression in 2 cases and loss of BAP1 and p53 in 1 case. Abnormal cytoplasmic BAP1 expression was observed in an additional case. Protein expression abnormalities correlated with NGS results, which showed concurrent complete genomic inactivation of CDKN2A/p16, CDKN2B, MTAP, and NF2 in 2 mesotheliomas and of BAP1 and TP53 in 1 mesothelioma each, respectively. In addition, 1 patient harbored a pathogenic BRCA1 germline mutation, which resulted in biallelic inactivation in the mesothelioma. All mesotheliomas were mismatch repair proficient and showed several chromosomal gains and losses. All patients died from disease. Our study demonstrates that pericardial mesotheliomas share common morphologic, immunohistochemical, and molecular genetic features with pleural mesothelioma, including recurrent genomic inactivation of canonical tumor suppressors. Our study adds new insights into the genetic landscape of primary pericardial mesothelioma and highlights BRCA1 loss as a potential contributing factor in a subset of cases, thereby contributing to refined precision diagnostics for this rare cancer.
Insights
Primary pericardial mesotheliomas, a rare cancer, share genetic similarities with pleural mesothelioma. Key tumor suppressor gene losses, including BRCA1, were identified, aiding in diagnosis.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Primary pericardial mesothelioma is extremely rare (<1% of all mesotheliomas).
- Molecular genetic features and predisposing factors are largely unknown.
- Understanding these aspects is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate the clinicopathologic, immunohistochemical, and molecular genetic features of primary pericardial mesotheliomas.
- To identify potential predisposing factors and genetic alterations.
- To compare findings with known features of pleural mesothelioma.
Main Methods:
- Analysis of 3 primary pericardial mesothelioma cases diagnosed between 2004 and 2022.
- Immunohistochemistry for tumor markers and suppressors (p16, MTAP, Merlin/NF2, BAP1, p53).
- Targeted next-generation sequencing (NGS) and germline mutation analysis (BRCA1).
Main Results:
- Two cases showed loss of p16, MTAP, and NF2; one case showed loss of BAP1 and TP53.
- Genomic inactivation of CDKN2A/p16, CDKN2B, MTAP, NF2, BAP1, and TP53 confirmed by NGS.
- One patient had a pathogenic BRCA1 germline mutation leading to biallelic inactivation.
Conclusions:
- Pericardial mesotheliomas share morphologic and molecular features with pleural mesothelioma, including tumor suppressor gene inactivation.
- BRCA1 loss is a potential contributing factor in a subset of these rare cancers.
- Findings contribute to refined precision diagnostics for primary pericardial mesothelioma.
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