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Association of acetylcholine receptor -subunit gene expression in mixed thymoma with myasthenia gravis

From the Institute of Pathology (Drs. Wilisch, Schultz, Müller-Hermelink, and Marx, and S. Gutsche and V. Hoffacker) and the Department of Neurology (Dr. Schneider), University of Würzburg; the Department of Neurology (Dr. Nix), University of Mainz; and the Department of Neurology (Dr. Schalke), University of Regensburg, Germany; and the Hellenic Pasteur Institute (Dr. Tzartos), Athens, Greece.

Address correspondence and reprint requests to Dr. Alexander Marx, Institute of Pathology, University of Würzburg, Josef-Schneider-Str. 2, D-97080, Würzburg, Germany.

OBJECTIVE: To investigate the association of MG with the transcription of muscular or neuronal acetylcholine receptor (AChR) subunit genes in thymomas.

BACKGROUND: Many steps in the pathogenesis of MG have been elucidated but, with rare exceptions, its etiology is unknown. In patients with MG with thymoma, the tumor probably elicits autoimmunity to AChR, but it is enigmatic why MG develops in some patients but not in others.

METHODS: Reverse transcriptase (RT)-PCR, immunohistochemistry, and immunofluorescence studies were carried out to investigate AChR expression in 35 patients with thymoma. Statistical analysis was used to specify significant differences between thymoma subtypes.

RESULTS: Considering all thymomas (n = 35), no correlation was found between MG status and AChR gene expression as detected by RT-PCR. However, when histologically defined thymoma subtypes were studied separately, transcription of the muscular AChR P3A^- -subunit gene was significantly associated ( < 0.01) with the occurrence of MG in mixed thymomas (n = 17), but not in thymomas of the cortical type. For the other muscular AChR subunits (P3A⁺ isoform, ß, , , and ) and the ₂ and ß₄ neuronal AChR subunits, no such correlation was detected.

CONCLUSIONS: Expression of the P3A^- AChR -subunit gene might be important for the pathogenesis of MG in mixed thymomas, suggesting etiologic heterogeneity of paraneoplastic MG among patients with histologically different thymoma subtypes.

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