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

Objective: To investigate the association of MG with the transcription of m uscular 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 t hymoma, the tumor probably elicits autoimmunity to AChR, but it is enigmati c why MG develops in some patients but not in others. Methods: Reverse tran scriptase (RT)-PCR, immunohistochemistry, and immunofluorescence studies we re carried out to investigate AChR expression in 35 patients with thymoma. Statistical analysis was used to specify significant differences between th ymoma 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 separat ely, transcription of the muscular AChR P3A(-) or-subunit gene was signific antly associated (alpha < 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(+) alpha isoform, beta, gamma, delta, and epsilon) and the alpha(2) and beta(4) neuronal AChR subunits, no such correlation was de tected. Conclusions: Expression of the P3A- AChR or-subunit gene might be i mportant for the pathogenesis of MG in mixed thymomas, suggesting etiologic heterogeneity of paraneoplastic MG among patients with histologically diff erent thymoma subtypes.