Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1992 Apr;140(4):839–845.

Immunocytochemical characteristics of small cell lung carcinoma associated with the Lambert-Eaton myasthenic syndrome.

C S Morris 1, M M Esiri 1, A Marx 1, J Newsom-Davis 1
PMCID: PMC1886379  PMID: 1314026

Abstract

The Lambert-Eaton myasthenic syndrome (LEMS) is characterized by the presence of IgG antibodies to motor nerve terminals, and associates with small cell lung carcinoma in more than 60% of cases. We have carried out a comparative immunocytochemical study on small cell lung carcinoma (SCLC) in five LEMS cases and six non-LEMS cases, using antibodies to tumor markers, MHC Class I and II, macrophages and lymphocytes. The authors found a reduced expression of the 200Kd neurofilament antigen and of MHC Class I antigens in the LEMS cases as well as a greater infiltration of activated macrophages. It is suggested that these findings are consistent with the view that SCLC antigenic determinants trigger the autoantibody response in SCLC-LEMS.

Full text

PDF
839

Images in this article

841Figure 1
on p.841
842Figure 6
on p.842
842Figure 7
on p.842

Selected References

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

  1. Babikian V. L., Stefansson K., Dieperink M. E., Arnason B. G., Marton L. S., Levy B. E. Paraneoplastic myelopathy: antibodies against protein in normal spinal cord and underlying neoplasm. Lancet. 1985 Jul 6;2(8445):49–50. doi: 10.1016/s0140-6736(85)90107-2. [DOI] [PubMed] [Google Scholar]
  2. Chalk C. H., Murray N. M., Newsom-Davis J., O'Neill J. H., Spiro S. G. Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma. Neurology. 1990 Oct;40(10):1552–1556. doi: 10.1212/wnl.40.10.1552. [DOI] [PubMed] [Google Scholar]
  3. Dalmau J., Furneaux H. M., Gralla R. J., Kris M. G., Posner J. B. Detection of the anti-Hu antibody in the serum of patients with small cell lung cancer--a quantitative western blot analysis. Ann Neurol. 1990 May;27(5):544–552. doi: 10.1002/ana.410270515. [DOI] [PubMed] [Google Scholar]
  4. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  5. Dämmrich J., Müller-Hermelink H. K., Mattner A., Buchwald J., Ziffer S. Histocompatibility antigen expression in pulmonary carcinomas as indication of differentiation and of special subtypes. Cancer. 1990 May 1;65(9):1942–1954. doi: 10.1002/1097-0142(19900501)65:9<1942::aid-cncr2820650912>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  6. Elmqvist D., Lambert E. H. Detailed analysis of neuromuscular transmission in a patient with the myasthenic syndrome sometimes associated with bronchogenic carcinoma. Mayo Clin Proc. 1968 Oct;43(10):689–713. [PubMed] [Google Scholar]
  7. Faustman D., Li X. P., Lin H. Y., Fu Y. E., Eisenbarth G., Avruch J., Guo J. Linkage of faulty major histocompatibility complex class I to autoimmune diabetes. Science. 1991 Dec 20;254(5039):1756–1761. doi: 10.1126/science.1763324. [DOI] [PubMed] [Google Scholar]
  8. Fukunaga H., Engel A. G., Lang B., Newsom-Davis J., Vincent A. Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7636–7640. doi: 10.1073/pnas.80.24.7636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graus F., Elkon K. B., Cordon-Cardo C., Posner J. B. Sensory neuronopathy and small cell lung cancer. Antineuronal antibody that also reacts with the tumor. Am J Med. 1986 Jan;80(1):45–52. doi: 10.1016/0002-9343(86)90047-1. [DOI] [PubMed] [Google Scholar]
  10. Graus F., Ribalta T., Campo E., Monforte R., Urbano A., Rozman C. Immunohistochemical analysis of the immune reaction in the nervous system in paraneoplastic encephalomyelitis. Neurology. 1990 Feb;40(2):219–222. doi: 10.1212/wnl.40.2.219. [DOI] [PubMed] [Google Scholar]
  11. Greenlee J. E., Lipton H. L. Anticerebellar antibodies in serum and cerebrospinal fluid of a patient with oat cell carcinoma of the lung and paraneoplastic cerebellar degeneration. Ann Neurol. 1986 Jan;19(1):82–85. doi: 10.1002/ana.410190117. [DOI] [PubMed] [Google Scholar]
  12. Grunwald G. B., Klein R., Simmonds M. A., Kornguth S. E. Autoimmune basis for visual paraneoplastic syndrome in patients with small-cell lung carcinoma. Lancet. 1985 Mar 23;1(8430):658–661. doi: 10.1016/s0140-6736(85)91326-1. [DOI] [PubMed] [Google Scholar]
  13. Jacobson D. M., Thirkill C. E., Tipping S. J. A clinical triad to diagnose paraneoplastic retinopathy. Ann Neurol. 1990 Aug;28(2):162–167. doi: 10.1002/ana.410280208. [DOI] [PubMed] [Google Scholar]
  14. Lang B., Newsom-Davis J., Peers C., Prior C., Wray D. W. The effect of myasthenic syndrome antibody on presynaptic calcium channels in the mouse. J Physiol. 1987 Sep;390:257–270. doi: 10.1113/jphysiol.1987.sp016698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lang B., Newsom-Davis J., Prior C., Wray D. Antibodies to motor nerve terminals: an electrophysiological study of a human myasthenic syndrome transferred to mouse. J Physiol. 1983 Nov;344:335–345. doi: 10.1113/jphysiol.1983.sp014943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lang B., Newsom-Davis J., Wray D., Vincent A., Murray N. Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome. Lancet. 1981 Aug 1;2(8240):224–226. doi: 10.1016/s0140-6736(81)90474-8. [DOI] [PubMed] [Google Scholar]
  17. Lang B., Vincent A., Murray N. M., Newsom-Davis J. Lambert-Eaton myasthenic syndrome: immunoglobulin G inhibition of Ca2+ flux in tumor cells correlates with disease severity. Ann Neurol. 1989 Mar;25(3):265–271. doi: 10.1002/ana.410250310. [DOI] [PubMed] [Google Scholar]
  18. Lennon V. A., Lambert E. H. Autoantibodies bind solubilized calcium channel-omega-conotoxin complexes from small cell lung carcinoma: a diagnostic aid for Lambert-Eaton myasthenic syndrome. Mayo Clin Proc. 1989 Dec;64(12):1498–1504. doi: 10.1016/s0025-6196(12)65705-x. [DOI] [PubMed] [Google Scholar]
  19. Leys K., Lang B., Johnston I., Newsom-Davis J. Calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. Ann Neurol. 1991 Mar;29(3):307–314. doi: 10.1002/ana.410290313. [DOI] [PubMed] [Google Scholar]
  20. McCann F. V., Pettengill O. S., Cole J. J., Russell J. A., Sorenson G. D. Calcium spike electrogenesis and other electrical activity in continuously cultured small cell carcinoma of the lung. Science. 1981 Jun 5;212(4499):1155–1157. doi: 10.1126/science.6262914. [DOI] [PubMed] [Google Scholar]
  21. Nagel A., Engel A. G., Lang B., Newsom-Davis J., Fukuoka T. Lambert-Eaton myasthenic syndrome IgG depletes presynaptic membrane active zone particles by antigenic modulation. Ann Neurol. 1988 Oct;24(4):552–558. doi: 10.1002/ana.410240412. [DOI] [PubMed] [Google Scholar]
  22. Napolitano L. A., Vogel J., Jay G. The role of major histocompatibility complex class I antigens in tumorigenesis: future applications in cancer therapy. Biochim Biophys Acta. 1989 Dec 17;989(2):153–162. doi: 10.1016/0304-419x(89)90040-1. [DOI] [PubMed] [Google Scholar]
  23. O'Neill J. H., Murray N. M., Newsom-Davis J. The Lambert-Eaton myasthenic syndrome. A review of 50 cases. Brain. 1988 Jun;111(Pt 3):577–596. doi: 10.1093/brain/111.3.577. [DOI] [PubMed] [Google Scholar]
  24. Roberts A., Perera S., Lang B., Vincent A., Newsom-Davis J. Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line. Nature. 1985 Oct 24;317(6039):737–739. doi: 10.1038/317737a0. [DOI] [PubMed] [Google Scholar]
  25. Sher E., Gotti C., Canal N., Scoppetta C., Piccolo G., Evoli A., Clementi F. Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic syndrome. Lancet. 1989 Sep 16;2(8664):640–643. doi: 10.1016/s0140-6736(89)90893-3. [DOI] [PubMed] [Google Scholar]
  26. Vincent A., Lang B., Newsom-Davis J. Autoimmunity to the voltage-gated calcium channel underlies the Lambert-Eaton myasthenic syndrome, a paraneoplastic disorder. Trends Neurosci. 1989 Dec;12(12):496–502. doi: 10.1016/0166-2236(89)90109-4. [DOI] [PubMed] [Google Scholar]
  27. Willcox N., Demaine A. G., Newsom-Davis J., Welsh K. I., Robb S. A., Spiro S. G. Increased frequency of IgG heavy chain marker Glm(2) and of HLA-B8 in Lambert-Eaton myasthenic syndrome with and without associated lung carcinoma. Hum Immunol. 1985 Sep;14(1):29–36. doi: 10.1016/0198-8859(85)90062-x. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES