Molecular biomarkers in malignant mesothelioma: state of the art

Our plain-English summary of Molecular biomarkers in malignant mesothelioma: state of the art, by S.C. Kao, G. Reid, N. van Zandwijk, et al (Pathology, 2011).

The study

• Authors: S.C. Kao, G. Reid, N. van Zandwijk, D.W. Henderson, S. Klebe
• Journal: Pathology
• Published: 2011;43(3):201-12
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive tumour affecting the mesothelial surfaces of the pleural and peritoneal cavities and, rarely, the pericardium and the tunica vaginalis testis. Despite a ban of asbestos in many industrialised nations, the present high incidence of MM is expected to continue, due to the long latency period between first asbestos exposure and occurrence of disease, making it an important health issue for the future. The diagnosis of MM can be difficult, both from a clinical and pathological perspective. It is not unusual for patients to undergo several medical investigations without definitive diagnosis early in their course of illness. Understandably, there is intense interest in the discovery of markers that can be assessed in pleural effusions, histological specimens, and serum to assist with the difficult early diagnosis of MM. Considering the primary aetiological role of asbestos, there is theoretically an easily identifiable target population for screening with a biomarker with adequate sensitivity and specificity or with a combination of biomarkers. In this review we focus on biomarkers that have been examined in the setting of either early diagnosis of MM in symptomatic patients or screening of asbestos-exposed individuals.

In plain English

This article was an invited review, not a new study. The authors reviewed published research on biomarkers measured in pleural fluid, tissue, blood or breath that had been examined for early diagnosis of malignant mesothelioma or for screening asbestos-exposed people. For soluble mesothelin-related proteins (SMRP) in blood, one early study reported 83% sensitivity and 95% specificity, but more recent studies showed sensitivity of 50% and specificity around 72%. In an Australian prospective screening study of 538 people with occupational asbestos exposure, 15 had high SMRP levels, yet no mesothelioma was detected. In a German cohort of 626 asbestos-exposed workers, SMRP, CA125 and CYFRA 21-1 each showed low sensitivity, and combining them did not improve it. The authors judged that a laboratory test (FISH) detecting deletion of the CDKN2A gene in the 9p21 chromosomal region was useful for telling reactive from cancerous mesothelial cells. In a Canadian CT screening study, screen-detected mesotheliomas were already advanced. The authors concluded that SMRP alone was not sensitive enough for screening and that they could not recommend large-scale serum screening.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Invited narrative review of published studies; no new data were collected
• Who was studied: No study population of its own. The authors reviewed published studies of biomarkers in pleural fluid, aspirates, tissue, serum, urine and breath, from patients with suspected or confirmed malignant mesothelioma and from asbestos-exposed people.
• Exposure: Asbestos exposure in general, described as the main cause of mesothelioma. The review did not study specific fiber types or doses; its subject is diagnostic and screening biomarkers.
• Main results:
  • Reported from another study (Robinson et al.): serum SMRP was suggested as a mesothelioma marker based on a sensitivity of 83% and a specificity of 95%.
  • Reported from more recent studies: SMRP had a lower sensitivity at diagnosis (50%) and specificities of around 72%.
  • Reported from a prospective New South Wales screening study of 538 patients with occupational asbestos exposure: high SMRP levels were found in 15 patients (3%), but not one case of mesothelioma was detected.
  • Reported from Gube et al., a retrospective study of 626 German asbestos-exposed workers: SMRP, CA125 and CYFRA 21-1 individually showed low sensitivity and positive predictive values, and combining them did not improve test sensitivity.
  • Homozygous loss of the CDKN2A gene within the common 9p21 chromosomal deletion, reported in 70–80% of mesotheliomas, has been explored as a diagnostic aid.
  • Reported from another study (Savic et al.): CDKN2A deletion was found by FISH in 41 of 52 cytology samples from patients with confirmed mesothelioma. All 28 benign effusions were FISH negative.
  • The authors' assessment: FISH-based detection of 9p21 deletion is especially useful for distinguishing reactive from neoplastic mesothelial cells.
  • Reported from a Canadian low-dose CT screening study of 516 asbestos-exposed individuals: the screen-detected mesotheliomas were already at an advanced stage, and the longest survival was 9 months.
• The authors' conclusion: The authors concluded that SMRP alone is not sensitive enough for mesothelioma screening and that no other marker or combination so far appears to improve on it. They stated that they cannot recommend large-scale serum screening for mesothelioma and that new approaches are needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Malignant Mesothelioma, State-of-the-Art Defense, Pericardium, Tunica Vaginalis, Latency, Asbestos Exposure, Discovery.

Related studies

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• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA — D.W. Henderson, G. Reid, et al. (2013)
• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers — D.W. Henderson, G. Reid, et al. (2013)
• ATG5 as biomarker for early detection of malignant mesothelioma — M. Tomasetti, F. Monaco, et al. (2023)
• Molecular tumor markers for asbestos-related mesothelioma: serum diagnostic markers — M. Maeda, O. Hino (2006)
• Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma — N.S. Patil, L. Righi, et al. (2018)

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