Clusters of chromosomal imbalances in thymic epithelial tumours indicate that tumorigenesis in thymomas is a continuum
Department of Pathology, University of Heidelberg, /221
Aim: The aim of the study was to identify different patterns of chromosomal aberrations associated with the biological behaviour and the histological diversity of thymomas. Methods: Using comparative genomic hybridisation we investigated chromosomal imbalances in 28 cases of thymic epithelial neoplasms including type A, B2, B3, the A component of type AB, and different subtypes of type C thymoma. A hierarchical cluster analysis of 65 cases was performed according to Eisen et al. (PNAS 1998;95:14863-68). The here reported CGH data (28 cases/ Penzel et al. Int J Cancer 2003;105:494-8) of partly uninvestigated tumour subtypes were pooled with previously published data of chromosomal imbalances of 37 thymomas (Zettl et al. Am J Pathol. 2001;159:1853-60). Results: The analysis of 278 chromosomal subbands yielded two main clusters. The first main cluster, characterised by gains of the chromosomal arm 1q, consisted only of type C and B3 thymomas and was further subdivided into two subgroups. To the first subgroup only thymomas were attributed which, in addition to gains of the chromosomal arm 1q, showed losses on 6q and 16q, whereas tumours belonging to the second subgroup exhibited no further recurrent chromosomal alterations. The second main cluster was formed by a heterogeneous group of thymoma types (types A, AB, B2, B3 and C), showing no specific pattern of chromosomal imbalances. In 19 thymomas no chromosomal imbalances could be detected (3 type B2 and 5 type A thymomas of this study as well as 11 type A thymomas investigated by Zettl et al.). Chromosomal imbalances were more frequent in type C thymomas than in other subtypes. The distribution of tumour stages according to Masaoka (p = 0.003) and the WHO classification (p < 0.0001) was significantly different in the clusters and subgroups obtained. Conclusions: Our analysis suggests that gains on the long arm of chromosome 1 occur early in tumor development followed by losses on chromosome 6 and 16q. Cluster analysis of chromosomal imbalances in thymomas reflects the staging system and the WHO classification and shows that type B3 and type C carcinomas have a strong relationship concerning their chromosomal imbalances. Furthermore, chromosomal imbalances detected in some type A thymomas might be responsible for the aggressive behaviour described in a few cases of this subtype. Our analysis favours the theory that tumorigenesis in thymomas is a continuum.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 796 (Genetic instability).