Retrospective Study Links BAP1 Loss to Lower Proliferation in Pleural Mesothelioma

A multicenter retrospective study of 50 patients with epithelioid mesothelioma has revealed that complete loss of BRCA1-associated protein 1 (BAP1) expression occurs predominantly in pleural tumors and correlates with lower tumor cell proliferation.

The research cohort was drawn from a multicenter mesothelioma database and comprised 50 patients with epithelioid mesothelioma and interpretable BAP1 immunohistochemistry, spanning 26 pleural and 24 peritoneal tumors.

Tumors were classified according to whether they exhibited complete nuclear BAP1 loss or retained expression, with Ki-67 proliferative activity standardized as the percentage of positive tumor cells.

Overall, complete BAP1 loss was identified in 17 of the 50 patients (34.0%), demonstrating a statistically significant association with the primary tumor site (P = 0.003) due to enriched loss in pleural cases.

Among the 36 patients with evaluable Ki-67 measurements across the entire cohort, median Ki-67 was 10.0% in cases with BAP1 loss compared to 15.0% in cases with retained expression (P = 0.150).

In pleural epithelioid mesothelioma specifically, proliferative activity was significantly lower in tumors with BAP1 loss, showing a median Ki-67 of 10.0% versus 50.0% for retained expression (P = 0.047), and mean values of 14.36% versus 39.44% (Welch’s t test, P = 0.028).

Survival evaluations indicated that BAP1 loss showed a trend toward longer progression-free survival in pleural tumors (hazard ratio = 0.36, 95% CI 0.12–1.09; P = 0.071). Using an exploratory combined model with a 10% Ki-67 cutoff, progression risk was significantly lower in the retained/low group (hazard ratio = 0.339, 95% CI 0.116–0.992; P = 0.048) and the loss/low group (hazard ratio = 0.202, 95% CI 0.056–0.727; P = 0.014) compared with the retained/high reference group.

The investigators concluded that although complete BAP1 deletion is enriched in pleural disease and associates with lower proliferation, the small sample size and favorable estimates in both low Ki-67 groups leave BAP1 without established independent prognostic value beyond Ki-67, requiring further validation in larger cohorts.

Subject of Research: BAP1 expression and tumor proliferation in epithelioid mesothelioma

Article Title: Association of BAP1 expression with clinicopathologic features, Ki-67 proliferative activity, and clinical outcomes in epithelioid mesothelioma: a multicenter retrospective study

Article References: Yang, S., Hong, J., Hao, Y., Guo, Z., Ji, Y., Xu, H., Meng, R., Zhang, Y., Xu, C., & Wang, Q. (2026). Association of BAP1 expression with clinicopathologic features, Ki-67 proliferative activity, and clinical outcomes in epithelioid mesothelioma: a multicenter retrospective study. Diagnostic Pathology. https://doi.org/10.1186/s13000-026-01872-x

Image Credits: AI Generated

DOI: 10.1186/s13000-026-01872-x

Keywords: epithelioid mesothelioma, BAP1 expression, Ki-67, pleural mesothelioma, peritoneal mesothelioma, tumor proliferation, progression-free survival, immunohistochemistry, Association, BAP1, expression, clinicopathologic