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(American Journal of Pathology. 2001;159:1853-1860.)
© 2001 American Society for Investigative Pathology

Regular Articles

Thymic Epithelial Tumors Can Develop along Two Different Pathogenetic Pathways

Ren Zhou*, Andreas Zettl{dagger}, Philipp Ströbel{dagger}, Kai Wagner{dagger}, Hans Konrad Müller-Hermelink{dagger}, Suo-jiang Zhang*, Alexander Marx{dagger} and Petr Starostik{dagger}

From the Institute of Pathology and Forensic Medicine,*
Zhejiang University Medical School, Zhejiang, China; and the Institute of Pathology,{dagger}
Würzburg University, Würzburg, Germany

To investigate genetic abnormalities associated with the development of thymic epithelial tumors, we performed microsatellite analysis of 26 thymomas belonging to three different World Health Organization types (A, B3, and C) using 48 repeats. The most frequent aberration seen was loss of heterozygosity (LOH) in the region 6q23.3-25.3 detected in 11 tumors (45.8% of informative cases). Further consistent LOHs were detected in regions 3p22-24.2, 3p14.2 (FHIT gene locus), 5q21 (APC), 6p21, 6q21-22.1, 7p21-22, 8q11.21-23, 13q14 (RB), and 17p13.1 (p53). Microsatellite instability was extremely rare, occurring in one type B3 thymoma only, although, at 12.5% of the analyzed loci. Comparing the allelotypes of the analyzed thymomas, we were able to identify two pathogenetic pathways these tumors develop along, characterized by the 6q23.3-25.3 and 5q21 LOHs, respectively. The APC aberration on 5q21 showed significant associations with LOH in the 3p22-24.2, 13q14, and 17p13.1 regions. Interestingly, type A thymomas presented with consistent LOH in the region 6q23.3-25.5 only, they did not reveal any aberrations in the APC, RB, and p53 gene loci or regions 3p22-24.2 and 8q11.21-23. The absence of these aberrations might be the reason for the well-known benign behavior of type A thymomas as compared to types B3 and C tumors.




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