Soft Tissue Sarcomas
Soft tissue sarcomas (STS) are uncommon tumours that present notable difficulties of diagnosis and classification. Leiomyosarcoma is one of the most common sub-types of STS. It presents in a number of characteristic anatomical sites and is notoriously resistant to conventional chemotherapeutic options. Little progress has been made in our understanding of the molecular basis of and treatment for this disease.
Comparative genomic hybridisation (CGH) can be used to detect amplified or deleted regions in DNA on a genome wide basis. DNA will be extracted from archived tissues and analysed by CGH. The findings will be correlated to the clinical presentation, stage and outcome, details of which are stored on the North Trent Sarcoma Database and from our collaborators.
The identification of specific genetic changes associated with leiomyosarcoma may provide new tools for approaching the molecular basis of this disease and for assisting diagnosis and treatment of this rare condition.
We plan to identify cases of leiomyosarcoma for which paraffin embedded or frozen tissue is available and, after expert pathological review, subject them to a range of genetic analyses in order to identify novel genetic changes. We will then correlate the genetic data obtained from the study with fully ascertained clinical parameters including site, grade, stage and outcome.
Background Information
Assigning a pathologic type or grade to an individual sarcoma as a means of predicting clinical behaviour is often difficult, with a 40% discordance rate even between expert sarcoma pathologists. (Singer et al, 1999). However, in recent years, genetic analyses of soft tissue sarcomas have provided a vast amount of new information. Karotypic analysis has revealed a number of specific aberrations in certain sub-types which have proved to be of use in diagnosis and in targeting treatment. In the case of synovial sarcoma, an t(X;18) translocation from which the involved genes have been identified is almost always present and can be used to directly assist in diagnosis. (Saboorian et al, 1997). Identification of c-kit over expression in gastrointestinal stromal sarcoma has allowed development of novel drugs blocking c-kit tyrosine kinase, one such drug is in early clinical trial at WPH.
However, in spite of these advances in some sub-types of sarcoma, and in the face of a number of preliminary genetic studies, the information available on leiomyosarcoma remains diverse and confusing.
