Manganese superoxide dismutase as a diagnostic marker for malignant pleural mesothelioma

Our plain-English summary of Manganese superoxide dismutase as a diagnostic marker for malignant pleural mesothelioma, by K. Kahlos, P. Pääkkö, E. Kurttila, et al (British Journal of Cancer, 2000).

The study

• Authors: K. Kahlos, P. Pääkkö, E. Kurttila, Y. Soini, V.L. Kinnula
• Journal: British Journal of Cancer
• Published: 2000;82(5):1022-9
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Although several immunohistochemical markers are available, differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura is difficult. We have found that the immunoreactivity of manganese superoxide dismutase (MnSOD), an important antioxidant enzyme, is high in mesothelioma compared to healthy pleural mesothelium. The aim of the present study was to investigate whether MnSOD can be used in the differential diagnosis of malignant mesothelioma and metastatic adenocarcinoma of the pleura. MnSOD expression was assessed by using immunohistochemistry in biopsies of malignant mesothelioma (n = 35) and metastatic adenocarcinoma of the pleura (n = 21). MnSOD immunoreactivity was assessed semiquantitatively with and without microwave pretreatment. Fifteen of the 35 malignant mesotheliomas showed moderate or strong MnSOD expression without and 23 with microwave pretreatment, the corresponding figures for metastatic adenocarcinoma of the pleura being 1 and 2 out of 21 (P = 0.002 and P < 0.001, respectively by Fisher's exact test). Only mesothelioma biopsies showed strong MnSOD reactivity, and it was never negative in mesothelioma, whereas one-third of the adenocarcinomas showed no MnSOD reactivity. In conclusion, MnSOD immunoreactivity can, combined with other markers, aid the differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma of the pleura.

In plain English

This Finnish laboratory study tested whether staining tissue for manganese superoxide dismutase (MnSOD), an antioxidant enzyme, could help pathologists tell malignant pleural mesothelioma apart from adenocarcinoma that had spread to the pleura. The authors re-examined stored pleural biopsies taken from 1976 to 1997 at Oulu University Hospital: 35 mesotheliomas and 21 metastatic adenocarcinomas. Of 24 mesothelioma patients with adequate data, 16 had occupational asbestos exposure according to their history. Without a microwave pretreatment, 15 of 35 mesotheliomas and 1 of 21 adenocarcinomas stained moderately or strongly (P = 0.002). With pretreatment the figures were 23 of 35 and 2 of 21 (P less than 0.001). Strong staining appeared only in mesotheliomas. After pretreatment no mesothelioma was negative, while one-third of the adenocarcinomas were. Staining did not differ by asbestos exposure history. Non-cancerous reactive mesothelium also stained strongly, so the authors said MnSOD cannot separate it from mesothelioma. Weak or negative staining leaves the diagnosis unclear. The authors concluded that MnSOD staining may be used as an additional diagnostic marker.

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: Retrospective laboratory (immunohistochemical) study of archived pleural biopsies, with Western blotting of cultured cell lines
• Who was studied: 56 patients (11 women, 45 men) with thoracoscopic pleural biopsies from 1976 to 1997, retrieved from the Department of Pathology, Oulu University Hospital, Finland. 35 had malignant mesothelioma (22 epithelial, 4 biphasic, 9 sarcomatoid per Table 1) and 21 had metastatic adenocarcinoma of the pleura. The study also tested seven mesothelioma cell lines, non-malignant Met5A mesothelial cells and A549 lung adenocarcinoma cells.
• Exposure: The study measured staining for the enzyme MnSOD, not an asbestos dose. Asbestos exposure was recorded from patient history only, and no fiber types are named. Of the 24 mesothelioma patients with adequate data, 16 (67%) had occupational asbestos exposure.
• Main results:
  • Mesotheliomas: 15 of 35 showed moderate or strong MnSOD staining without microwave pretreatment and 23 of 35 after it.
  • Metastatic adenocarcinomas of the pleura: 1 of 21 showed moderate or strong staining without pretreatment and 2 of 21 after it. The difference from mesothelioma was P = 0.002 without pretreatment and P less than 0.001 after it, by Fisher's exact test.
  • Strong MnSOD staining occurred only in mesotheliomas and in none of the metastatic adenocarcinomas.
  • After microwave pretreatment, none of the mesothelioma biopsies were negative. One-third of the 21 adenocarcinoma biopsies (6 of 21 per Table 6) were still negative.
  • Within mesothelioma, strong staining occurred only in epithelial and biphasic types, not in sarcomatoid types (P = 0.03 without pretreatment, P = 0.02 after it).
  • MnSOD staining did not differ between mesothelioma patients with and without previous asbestos exposure.
  • Mesothelioma patients with moderate or strong staining after pretreatment had slightly better short-term, but not long-term, survival than those with negative or weak staining. Median survival was 8 versus 2 months (P = 0.057 by log-rank test; P = 0.008 by Breslow test).
  • In cultured cells, all seven mesothelioma cell lines showed higher MnSOD levels than the non-malignant Met5A mesothelial cells.
• The authors' conclusion: The authors concluded that MnSOD staining may be used as an additional diagnostic marker for telling malignant mesothelioma apart from metastatic adenocarcinoma of the pleura.
• Limitations the authors state:
  • MnSOD also rises in non-malignant reactive mesothelium, so it cannot separate reactive mesothelium from malignant mesothelioma.
  • When staining is weak or negative, the test does not resolve whether the tumour is mesothelioma or adenocarcinoma.
  • Asbestos exposure information was collected retrospectively and may undercount exposed patients.
  • The survival differences were very small.
  • The staining methods are semiquantitative and may vary between laboratories.

Topics

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

Medical terms in this study, explained in our Lexicon: Superoxide, Pleural Mesothelioma, Differential Diagnosis, Mesothelioma, Adenocarcinoma, Pleura, Mesothelium, Immunohistochemistry.

Related studies

• Ultrastructural and chromosomal studies on manganese superoxide dismutase in malignant mesothelioma — V.L. Kinnula, T. Torkkeli, et al. (2004)
• Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma — K. Kahlos, S. Anttila, et al. (1998)
• Manganese superoxide dismutase in human pleural mesothelioma cell lines — V.L. Kinnula, P. Pietarinen-Runtti, et al. (1996)
• Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma — S. Landi, F. Gemignani, et al. (2007)
• Transfection of a manganese-containing superoxide dismutase gene into hamster tracheal epithelial cells ameliorates asbestos-mediated cytotoxicity — B.T. Mossman, P. Surinrut, et al. (1996)
• Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk — L.I. Wang, D. Neuberg, et al. (2004)

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