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.
Background In patients with cancer, symptoms of limbic and brain-stemdysfunction may result from a paraneoplastic disorder. Paraneoplasticlimbic or brain-stem encephalitis occurs more frequently withtesticular cancer than with most other cancers. We sought antineuronalantibodies that might be used in a diagnostic test for thissyndrome.
Methods Immunohistochemical and immunoblotting techniques wereused to detect serum and cerebrospinal fluid antibodies. Serologicscreening of a complementary DNA library and Northern blottingwere used to clone the target antigen and determine which tissuesexpressed it.
Results Of 13 patients with testicular cancer and paraneoplasticlimbic or brain-stem encephalitis (or both), 10 had antibodiesin 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 serumfrom the 10 patients, but not by serum from 344 control subjects.Ma2 was selectively expressed by normal brain tissue and bythe testicular tumors of the patients. Ma2 shares homology withMa1, a "braintestiscancer" gene related to otherparaneoplastic syndromes and tumors.
Conclusions The serum of patients with subacute limbic and brain-stemdysfunction and testicular cancer contains antibodies againsta protein found in normal brain and in testicular tumors. Detectionof these antibodies supports the paraneoplastic origin of theneurologic disorder and could be of diagnostic importance.
Source Information
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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