Immune response profiling of malignant pleural mesothelioma for diagnostic and prognostic biomarkers.

The asbestos induced cancer malignant mesothelioma (MM) is difficult to diagnose and has a poor prognosis. MM is an immunological cancer, therefore autoantibodies may be suitable biomarkers and associated with prognosis. We used Protoarray(®) microarrays to determine immune responses to 8798 antigens in 10 MM and 10 asbestos exposed controls and developed diagnostic panels using 17 antigens from this. The AUC of these panels were independently tested in these 10 MM patients and controls and in a validation group of 36 controls and 35 MM patients using luminex assays; none of the antigens identified were validated. Immune responses to RAB38 were associated with a better prognosis.

Increasing incidence of malignant mesothelioma after exposure to asbestos during home maintenance and renovation.

OBJECTIVE: To determine trends in incidence of malignant mesothelioma (MM) caused by exposure to asbestos during home maintenance and renovation. DESIGN, SETTING AND PARTICIPANTS: Using the Western Australian Mesothelioma Register, we reviewed all cases of MM diagnosed in WA from 1960 to the end of 2008, and determined the primary source of exposure to asbestos. Categories of exposure were collapsed into seven groups: asbestos miners and millers from Wittenoom; all other asbestos workers; residents from Wittenoom; home maintenance/renovators; other people exposed but not through their occupation; and people with unknown asbestos exposure; or no known asbestos exposure. Latency periods and age at diagnosis for each group were calculated and compared. RESULTS: In WA, 1631 people (1408 men, 223 women) were diagnosed with MM between 1960 and 2008. Since 1981, there have been 87 cases (55 in men) of MM attributed to asbestos exposure during home maintenance and renovation, and an increasing trend in such cases, in both men and women. In the last 4 years of the study (2005-2008), home renovators accounted for 8.4% of all men and 35.7% of all women diagnosed with MM. After controlling for sex and both year and age at diagnosis, the latency period for people exposed to asbestos during home renovation was significantly shorter than that for all other exposure groups, but the shorter follow-up and difficulty recalling when exposure first occurred in this group may partly explain this. CONCLUSIONS: MM after exposure to asbestos during home renovation is an increasing problem in WA, and these cases seem to have a shorter latency period than other types of exposure. MM cases related to renovation will probably continue to increase because of the many homes that have contained, and still contain, asbestos building products.

Asbestos-related disease from recycled hessian superphosphate bags in rural Western Australia.

OBJECTIVES: To describe the dissemination of asbestos fibres within the Western Australian community. METHODS: A case report. RESULTS: A 60-year-old female was referred for investigation of calcified pleural plaques. On questioning, she recalled exposure to asbestos as a child on the family farm. She had shaken hessian bags prior to recycling to the fertiliser supplier. Her father survived to 90 years. Her mother died from malignant pleural mesothelioma. Four of five siblings had shaken the bags, two had radiographic evidence of pleural plaques while two others had not had recent chest x-rays. CONCLUSIONS: It appears that the use of recycled hessian bags for the fertiliser industry was endemic in the State during the period 1943-66. It is possible that many farmers and their families have had similar exposure to asbestos. IMPLICATIONS: The risk of developing an asbestos-related disease is not restricted to any specific social or employment groups within the Australian community.

Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol.

OBJECTIVE: Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007. METHODS: Participants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5 mg RE/d) or beta-carotene (30 mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models. RESULTS: Over a median follow-up of 7.8 y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86 µmol/L; 95% confidence interval [CI], 0.65-1.14) or osteoporotic fracture (HR, 0.97 µmol/L; 95% CI, 0.66-1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85 µmol/L; 95% CI, 0.71-1.01). CONCLUSIONS: This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation.

A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit.

AIMS: Cytological diagnosis of malignant pleural mesothelioma (MPM) is controversial, but has been used in our institution for over 30 years. To assess the role of effusion cytology in mesothelioma diagnosis we conducted an audit of pleural fluid cytology results over a 20 year period (1988-2007). METHODS: Pleural samples were received from 6285 patients; data linkage with Western Australian Cancer and Mesothelioma Registries demonstrated that 815 of these patients had a diagnosis of MPM. Cytological examination of a pleural effusion specimen had been performed in 517 (63%) of these 815 patients. RESULTS: Definitive cytological diagnosis of MPM was made in 377/517 cases, resulting in an 'absolute' sensitivity of 73%. An additional 66 patients were diagnosed as atypical/suspicious, resulting in a 'complete' sensitivity of 86%. If only biopsy/necropsy proven cases are considered, the absolute sensitivity is 68% and the complete sensitivity is 82%. There were no false positive diagnoses of malignancy; two patients with metastatic adenocarcinoma were initially diagnosed as MPM, prior to the availability of specific mesothelial markers, resulting in a positive predictive value of 99%. CONCLUSIONS: Effusion cytology is an inexpensive, minimally invasive procedure which should be included in the diagnostic work-up of cases of suspected MPM.

Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma.

BACKGROUND: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a useful screening test for asbestos-exposed at-risk individuals. In this study, soluble mesothelin was determined in sequential serum samples collected from asbestos-exposed individuals before the development of mesothelioma. METHODS: Archival serum samples from 106 individuals who developed mesothelioma, 99 asbestos-exposed individuals from the Wittenoom Cancer Surveillance Program, and 109 non-asbestos-exposed individuals from the Busselton Health Survey were identified. Serum mesothelin concentrations were determined using the MESOMARK assay. RESULTS: Longitudinal mesothelin levels determined in healthy asbestos-exposed individuals over a period of 4 years were stable (Pearson's r = 0.96; P < 0.0001). There was no correlation between mesothelin concentration and cumulative asbestos exposure. Mesothelin concentrations were greater than the threshold value of 2.5 nmol/L in the penultimate serum sample before the diagnosis of mesothelioma in 17 of 106 people. Using an increase above the 95% confidence interval of the mean of a given individual's longitudinal mesothelin results, 33 of 82 individuals had increasing mesothelin levels before diagnosis. CONCLUSION: In a population with a high pretest probability of developing mesothelioma, the serum biomarker mesothelin is elevated in absolute terms in 15% and in relative terms in 40% of the group. IMPACT: Future studies examining a combination of biomarkers could improve sensitivity of screening.