Soft tissue tumours: the impact of cytogenetics and molecular genetics

Cytogenetic and molecular analysis of soft tissue tumours has yielded a wealth of new information over the past 10-15 years. Many soft tissue neoplasms show specific karyotypic aberrations which have proved to be diagnostically valuable, and have also assisted in the understanding of pathogenetic mechanisms and rationalisation of classification systems (e.g. lipomatous tumours and Ewing's sarcoma/PNET). In certain clinical subsets, especially round cell sarcomas and fatty neoplasms, determination of karyotype (whether by conventional analysis, FISH or RT-PCR) has proved often to be useful in the diagnostic setting. Additionally the recognition of clonal abnormalities in both benign neoplasms as well as lesions formerly thought to be non-neoplastic (e.g. inflammatory "pseudotumour") has prompted reassessment of biologic concepts with regard to growth control. Inherited molecular genetic defects which predispose to soft tissue neoplasia (e.g. NF-1, Li-Fraumeni syndrome) have been characterised, leading to a greater understanding of tumour suppressor genes. Mesenchymal differentiation genes, the modes of action of which may help to expunge concepts of histogenesis, are being characterised. It is becoming clear that there exist growth control genes (such as the HMGI family) which, irrespective of differentiation, play an important role in a wide range of different mesenchymal tumours. Additionally it is evident that different histologic types of sarcoma (e.g. variants of liposarcoma) show quite different abnormalities of cell cycle control (notably at the G1-S checkpoint) and it seems increasingly likely that certain genetic aberrations, identifiable either at the chromosomal or individual gene level, may prove to be of prognostic relevance in sarcomas and may also open novel therapeutic avenues. While the validity of all molecular genetic data depends totally on skilled histological diagnosis and grading, there has never been a better time for close collaboration between pathologists and basic scientists in the study of soft tissue neoplasia.