Related Experiment Video
Updated: Aug 3, 2025
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Surgical phenotype of patients with peritoneal mesothelioma and a germline mutation
Yaniv Berger1, Meghana Gadiraju2, Ankit Dhiman3
1Department of Surgery, Sheba Medical Center, Tel Hashomer, Affiliated to the Tel-Aviv University, Tel-Aviv, Israel.
Background:
This study aimed to investigate if peritoneal mesothelioma (PM) patients with germline mutations (GM) have distinct surgical characteristics when compared to those without GM.
Methods:
PM patients were selected from an ongoing prospective study that conducts germline testing of 82 susceptibility genes. Germline status was correlated with surgical data obtained from a prospectively collected database using univariate, multivariate, and receiver operating characteristic (ROC) analyses.
Results:
Out of 88 PM patients enrolled between 2009 and 2019, 18 GMs (20.5%) were identified in BRCA1-associated protein 1 (BAP1) (n = 11, 12.5% of all patients), SDHA (n = 2) and WT1, CDKN2A, CHEK2, ATM, and BRCA2 (n = 1 patient each). Surgical procedures were performed in 71 patients, the most common of which were cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy (n = 61). Patients with GM presented with a higher prevalence of other prior cancers (61.1% vs. 31.4%, p = .02) and lower platelet count (251 [160-413] vs. 367 [196-780] K/µL, p = .005) compared to those without GM (n = 70). Survival outcomes did not differ significantly between the groups. Patients with BAP1 GMs were more likely to develop bicavitary disease and to present with lower platelet count and mitotic count score, and higher peritoneal cancer index (PCI, all p ≤ .04) compared with those without GM. On ROC analysis, the combination of PCI, platelet count and mitotic score yielded an area under the curve of 0.96 (95% CI, 0.91-1.0) for BAP1 GM detection among operated PM patients.
Conclusion:
Higher intraoperative tumor burden and lower platelet count and mitotic score are suggestive of BAP1 GMs in surgical PM patients and should prompt germline testing.
Insights
Peritoneal mesothelioma patients with germline mutations (GM) show distinct surgical traits, including higher prior cancer rates and lower platelet counts. BAP1 GMs are linked to increased tumor burden and lower platelet counts, suggesting germline testing.
Area of Science:
- Oncology
- Genetics
- Surgical Pathology
Background:
- Peritoneal mesothelioma (PM) is a rare cancer.
- Germline mutations (GM) may influence disease presentation and surgical characteristics.
- Investigating GM in PM patients is crucial for understanding disease heterogeneity.
Purpose of the Study:
- To determine if peritoneal mesothelioma patients with germline mutations exhibit distinct surgical characteristics compared to those without.
- To identify specific surgical features associated with germline mutations in PM.
Main Methods:
- Prospective study of 88 PM patients undergoing germline testing for 82 susceptibility genes.
- Correlation of germline status with surgical data using univariate, multivariate, and ROC analyses.
- Analysis of 71 patients who underwent surgical procedures, primarily cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.
Main Results:
- 18.2% of PM patients had identified germline mutations, predominantly in BAP1 (12.5%).
- Patients with GM had a higher prevalence of prior cancers (61.1% vs. 31.4%) and lower platelet counts (p=0.005).
- BAP1 GMs were associated with higher tumor burden (bicavitary disease, PCI) and lower platelet/mitotic counts (p≤0.04).
Conclusions:
- Elevated intraoperative tumor burden and reduced platelet/mitotic counts suggest BAP1 germline mutations in surgical PM patients.
- These findings support germline testing in PM patients with specific surgical characteristics.
- Surgical characteristics can aid in identifying PM patients who may benefit from germline genetic testing.
