Background In the Western World malignant mesothelioma (MM) is most prevalent in the pleura of older males professionally exposed to asbestos. Information about MM from rapidly industrializing countries, such as China, is minimal. There is concern that a proportion of MM diagnoses in China may be incorrect because most Chinese physicians do not have experience diagnosing this rare cancer. We recently reported an unusual high incidence of peritoneal MM among Eastern Chinese female patients. Here, we review the accuracy of MM diagnoses in China and provide suggestions to improve the accuracy of diagnosis. Methods We reviewed 92 pathological diagnosis of MM during 2002–2015 from two reference centers in the province of Zhejiang, Eastern China. We performed, a large set of immunohistochemical (IHC) analyses to increase the reliability of the diagnosis. Results We confirmed the MM diagnosis in 12/34 (35.3%) of the pleural tumors, in 38/56 (67.9%) of the peritoneal tumors, and in 2/2 (100%) of the MM of the tunica vaginalis. MM were characterized by tumor cells showing nuclear WT1 and calretinin staining and by strong membranous staining for cytokeratin (CK) CAM5.2. The epithelial markers, CEA, TTF1, MOC31, BerEP4, p63, p40, PAX8, ER and PR were negative. BAP1 nuclear staining was lost in percentages similar to what reported for samples from Western countries. Conclusions Our findings suggest that MM –especially in its pleural localization– is often misdiagnosed in Eastern China. Identifying pitfalls and possible solutions in the pathological diagnosis of MM will impact both standard of care and research in China.

This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma.

No abstract

While chrysotile has been commonly used by Chinese textile industry for many years, investigations on the association of chrysotile exposure with risk of mesothelioma in China are scarce. We conducted a case-control study in a county located at Southeastern China, including 46 cases and 230 individually matched controls. A semi-quantitative method based on experts' assessment was used for evaluating hand-spinning chrysotile exposure. Conditional logistic regression models were used to assess the association of asbestos exposure with risk of mesothelioma. We found that hand-spinning chrysotile exposure was associated with significantly elevated risk of mesothelioma, reaching OR =10 (95% CIs: 1.4-65) for possible exposure and 64 (12-328) for definite exposure. Our data suggested a dose-response relationship of chrysotile exposure duration with risk of mesothelioma, reaching 28 (6-134) for <6 years, 51 (11-247) for 7-17 years and 56 (9-351) for ≥18 years. A dose-response relationship of cumulative exposure index (CEI) with risk of mesothelioma was found, reaching 28 (6-137) for CEI at 0-0.5 fibers per milliliter years (f/mL-year), 36 (7-184) for CEI at 0.5-28.6 f/mL-years and 79 (14-451) for CEI > 28.6 f/mL-years. We found a dose-response relationship of chrysotile exposure duration and CEI with risk of mesothelioma in Southeastern China, adding valuable information on health hazards of chrysotile exposure in China where chrysotile is still used nationwide.

Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient’s HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM.