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Original Article
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Volume 340:1788-1795 June 10, 1999 Number 23
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A Serologic Marker of Paraneoplastic Limbic and Brain-Stem Encephalitis in Patients with Testicular Cancer
Raymond Voltz, M.D., S. Humayun Gultekin, M.D., Myrna R. Rosenfeld, M.D., Ph.D., Elizabeth Gerstner, B.S., Joseph Eichen, M.S., Jerome B. Posner, M.D., and Josep Dalmau, M.D., Ph.D.

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ABSTRACT

Background In patients with cancer, symptoms of limbic and brain-stem dysfunction may result from a paraneoplastic disorder. Paraneoplastic limbic or brain-stem encephalitis occurs more frequently with testicular cancer than with most other cancers. We sought antineuronal antibodies that might be used in a diagnostic test for this syndrome.

Methods Immunohistochemical and immunoblotting techniques were used to detect serum and cerebrospinal fluid antibodies. Serologic screening of a complementary DNA library and Northern blotting were used to clone the target antigen and determine which tissues expressed it.

Results Of 13 patients with testicular cancer and paraneoplastic limbic or brain-stem encephalitis (or both), 10 had antibodies in serum and cerebrospinal fluid against a 40-kd neuronal protein. These antibodies were used to clone a gene that we call Ma2, which codes for a protein (Ma2) that was recognized by serum from the 10 patients, but not by serum from 344 control subjects. Ma2 was selectively expressed by normal brain tissue and by the testicular tumors of the patients. Ma2 shares homology with Ma1, a "brain–testis–cancer" gene related to other paraneoplastic syndromes and tumors.

Conclusions The serum of patients with subacute limbic and brain-stem dysfunction and testicular cancer contains antibodies against a protein found in normal brain and in testicular tumors. Detection of these antibodies supports the paraneoplastic origin of the neurologic disorder and could be of diagnostic importance.


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From the Department of Neurology and the Cotzias Laboratory of Neuro-Oncology (R.V., S.H.G., M.R.R., E.G., J.E., J.B.P., J.D.) and the Department of Pathology (S.H.G.), Memorial Sloan-Kettering Cancer Center, New York.

Address reprint requests to Dr. Dalmau at the Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, or at dalmauj{at}mskcc.org.

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Related Letters:

A Serologic Marker of Paraneoplastic Limbic and Brain-Stem Encephalitis in Patients with Testicular Cancer
Debourdeau P., Gligorov J., Zammit C., Dalmau J., Gultekin H. S., Posner J. B.
Extract | Full Text  
N Engl J Med 1999; 341:1475-1476, Nov 4, 1999. Correspondence

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