Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Feb 1;82(5):1022–1029. doi: 10.1054/bjoc.1999.1037

Manganese superoxide dismutase as a diagnostic marker for malignant pleural mesothelioma

K Kahlos 1, P Pääkkö 2, E Kurttila 1, Y Soini 2, V L Kinnula 1
PMCID: PMC2374425  PMID: 10737384

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. © 2000Cancer Research Campaign

Keywords: mesothelioma, metastatic adenocarcinoma, diagnosis, manganese superoxide dismutase, immunohistochemistry

Full Text

The Full Text of this article is available as a PDF (175.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  2. Clyde B. L., Chang L. Y., Auten R. L., Ho Y. S., Crapo J. D. Distribution of manganese superoxide dismutase mRNA in normal and hyperoxic rat lung. Am J Respir Cell Mol Biol. 1993 May;8(5):530–537. doi: 10.1165/ajrcmb/8.5.530. [DOI] [PubMed] [Google Scholar]
  3. Cobbs C. S., Levi D. S., Aldape K., Israel M. A. Manganese superoxide dismutase expression in human central nervous system tumors. Cancer Res. 1996 Jul 15;56(14):3192–3195. [PubMed] [Google Scholar]
  4. Coursin D. B., Cihla H. P., Sempf J., Oberley T. D., Oberley L. W. An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung. Histol Histopathol. 1996 Oct;11(4):851–860. [PubMed] [Google Scholar]
  5. Dejmek A., Hjerpe A. Carcinoembryonic antigen-like reactivity in malignant mesothelioma. A comparison between different commercially available antibodies. Cancer. 1994 Jan 15;73(2):464–469. doi: 10.1002/1097-0142(19940115)73:2<464::aid-cncr2820730235>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  6. Gaffey M. J., Mills S. E., Swanson P. E., Zarbo R. J., Shah A. R., Wick M. R. Immunoreactivity for BER-EP4 in adenocarcinomas, adenomatoid tumors, and malignant mesotheliomas. Am J Surg Pathol. 1992 Jun;16(6):593–599. doi: 10.1097/00000478-199206000-00007. [DOI] [PubMed] [Google Scholar]
  7. Janssen A. M., Bosman C. B., Sier C. F., Griffioen G., Kubben F. J., Lamers C. B., van Krieken J. H., van de Velde C. J., Verspaget H. W. Superoxide dismutases in relation to the overall survival of colorectal cancer patients. Br J Cancer. 1998 Oct;78(8):1051–1057. doi: 10.1038/bjc.1998.626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Janssen Y. M., Marsh J. P., Driscoll K. E., Borm P. J., Oberdörster G., Mossman B. T. Increased expression of manganese-containing superoxide dismutase in rat lungs after inhalation of inflammatory and fibrogenic minerals. Free Radic Biol Med. 1994 Mar;16(3):315–322. doi: 10.1016/0891-5849(94)90032-9. [DOI] [PubMed] [Google Scholar]
  9. Kahlos K., Anttila S., Asikainen T., Kinnula K., Raivio K. O., Mattson K., Linnainmaa K., Kinnula V. L. Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma. Am J Respir Cell Mol Biol. 1998 Apr;18(4):570–580. doi: 10.1165/ajrcmb.18.4.2943. [DOI] [PubMed] [Google Scholar]
  10. Ke Y., Reddel R. R., Gerwin B. I., Reddel H. K., Somers A. N., McMenamin M. G., LaVeck M. A., Stahel R. A., Lechner J. F., Harris C. C. Establishment of a human in vitro mesothelial cell model system for investigating mechanisms of asbestos-induced mesothelioma. Am J Pathol. 1989 May;134(5):979–991. [PMC free article] [PubMed] [Google Scholar]
  11. Kinnula V. L., Chang L., Everitt J. I., Crapo J. D. Oxidants and antioxidants in alveolar epithelial type II cells: in situ, freshly isolated, and cultured cells. Am J Physiol. 1992 Jan;262(1 Pt 1):L69–L77. doi: 10.1152/ajplung.1992.262.1.L69. [DOI] [PubMed] [Google Scholar]
  12. Kinnula V. L., Crapo J. D., Raivio K. O. Generation and disposal of reactive oxygen metabolites in the lung. Lab Invest. 1995 Jul;73(1):3–19. [PubMed] [Google Scholar]
  13. Kinnula V. L., Pietarinen-Runtti P., Raivio K., Kahlos K., Pelin K., Mattson K., Linnainmaa K. Manganese superoxide dismutase in human pleural mesothelioma cell lines. Free Radic Biol Med. 1996;21(4):527–532. doi: 10.1016/0891-5849(96)00049-4. [DOI] [PubMed] [Google Scholar]
  14. Kinnula V. L., Yankaskas J. R., Chang L., Virtanen I., Linnala A., Kang B. H., Crapo J. D. Primary and immortalized (BEAS 2B) human bronchial epithelial cells have significant antioxidative capacity in vitro. Am J Respir Cell Mol Biol. 1994 Nov;11(5):568–576. doi: 10.1165/ajrcmb.11.5.7946385. [DOI] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Lakari E., Päkkö P., Kinnula V. L. Manganese superoxide dismutase, but not CuZn superoxide dismutase, is highly expressed in the granulomas of pulmonary sarcoidosis and extrinsic allergic alveolitis. Am J Respir Crit Care Med. 1998 Aug;158(2):589–596. doi: 10.1164/ajrccm.158.2.9711059. [DOI] [PubMed] [Google Scholar]
  17. Landriscina M., Remiddi F., Ria F., Palazzotti B., De Leo M. E., Iacoangeli M., Rosselli R., Scerrati M., Galeotti T. The level of MnSOD is directly correlated with grade of brain tumours of neuroepithelial origin. Br J Cancer. 1996 Dec;74(12):1877–1885. doi: 10.1038/bjc.1996.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Leers M. P., Aarts M. M., Theunissen P. H. E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma. Histopathology. 1998 Mar;32(3):209–216. doi: 10.1046/j.1365-2559.1998.00349.x. [DOI] [PubMed] [Google Scholar]
  19. Mossman B. T., Kamp D. W., Weitzman S. A. Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers. Cancer Invest. 1996;14(5):466–480. doi: 10.3109/07357909609018904. [DOI] [PubMed] [Google Scholar]
  20. Mossman B. T., Marsh J. P., Shatos M. A. Alteration of superoxide dismutase activity in tracheal epithelial cells by asbestos and inhibition of cytotoxicity by antioxidants. Lab Invest. 1986 Feb;54(2):204–212. [PubMed] [Google Scholar]
  21. Nishida S., Akai F., Iwasaki H., Hosokawa K., Kusunoki T., Suzuki K., Taniguchi N., Hashimoto S., Tamura T. T. Manganese superoxide dismutase content and localization in human thyroid tumours. J Pathol. 1993 Mar;169(3):341–345. doi: 10.1002/path.1711690311. [DOI] [PubMed] [Google Scholar]
  22. Oberley L. W., Buettner G. R. Role of superoxide dismutase in cancer: a review. Cancer Res. 1979 Apr;39(4):1141–1149. [PubMed] [Google Scholar]
  23. Pelin-Enlund K., Husgafvel-Pursiainen K., Tammilehto L., Klockars M., Jantunen K., Gerwin B. I., Harris C. C., Tuomi T., Vanhala E., Mattson K. Asbestos-related malignant mesothelioma: growth, cytology, tumorigenicity and consistent chromosome findings in cell lines from five patients. Carcinogenesis. 1990 Apr;11(4):673–681. doi: 10.1093/carcin/11.4.673. [DOI] [PubMed] [Google Scholar]
  24. Pelin K., Hirvonen A., Linnainmaa K. Expression of cell adhesion molecules and connexins in gap junctional intercellular communication deficient human mesothelioma tumour cell lines and communication competent primary mesothelial cells. Carcinogenesis. 1994 Nov;15(11):2673–2675. doi: 10.1093/carcin/15.11.2673. [DOI] [PubMed] [Google Scholar]
  25. Pietarinen-Runtti P., Raivio K. O., Linnainmaa K., Ekman A., Saksela M., Kinnula V. L. Differential effects of tumor necrosis factor and asbestos fibers on manganese superoxide dismutase induction and oxidant-induced cytotoxicity in human mesothelial cells. Cell Biol Toxicol. 1996 Jun;12(3):167–175. doi: 10.1007/BF00148170. [DOI] [PubMed] [Google Scholar]
  26. Ruitenbeek T., Gouw A. S., Poppema S. Immunocytology of body cavity fluids. MOC-31, a monoclonal antibody discriminating between mesothelial and epithelial cells. Arch Pathol Lab Med. 1994 Mar;118(3):265–269. [PubMed] [Google Scholar]
  27. Tsan M. F., White J. E., Santana T. A., Lee C. Y. Tracheal insufflation of tumor necrosis factor protects rats against oxygen toxicity. J Appl Physiol (1985) 1990 Mar;68(3):1211–1219. doi: 10.1152/jappl.1990.68.3.1211. [DOI] [PubMed] [Google Scholar]
  28. Ungar S., Van de Meeren A., Tammilehto L., Linnainmaa K., Mattson K., Gerwin B. I. High levels of MDM2 are not correlated with the presence of wild-type p53 in human malignant mesothelioma cell lines. Br J Cancer. 1996 Nov;74(10):1534–1540. doi: 10.1038/bjc.1996.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Van Driel B. E., Lyon H., Hoogenraad D. C., Anten S., Hansen U., Van Noorden C. J. Expression of CuZn- and Mn-superoxide dismutase in human colorectal neoplasms. Free Radic Biol Med. 1997;23(3):435–444. doi: 10.1016/s0891-5849(97)00102-0. [DOI] [PubMed] [Google Scholar]
  30. Wispé J. R., Warner B. B., Clark J. C., Dey C. R., Neuman J., Glasser S. W., Crapo J. D., Chang L. Y., Whitsett J. A. Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury. J Biol Chem. 1992 Nov 25;267(33):23937–23941. [PubMed] [Google Scholar]
  31. Wong G. H., Goeddel D. V. Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism. Science. 1988 Nov 11;242(4880):941–944. doi: 10.1126/science.3263703. [DOI] [PubMed] [Google Scholar]
  32. van der Kwast T. H., Versnel M. A., Delahaye M., de Jong A., Zondervan P. E., Hoogsteden H. Expression of epithelial membrane antigen on malignant mesothelioma cells. An immunocytochemical and immunoelectron microscopic study. Acta Cytol. 1988 Mar-Apr;32(2):169–174. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES