Sarcomas, in strict analogy with tumours of the haematolymphoid organs, are frequently associated with relatively specific genetic alterations such as chromosome translocations, amplification of proto-oncogenes and loss of tumour suppressor genes. A significant number of sarcomas, pleomorphic sarcomas and leiomyosarcoma in particular, actually exhibit more complex genetic aberrations that still need further elucidation. Chromosome translocations not only shed light on the mechanism of sarcomagenesis but also represent a powerful diagnostic tool and can be effectively detected on routine histologic material. As with IHC, also molecular genetic findings need to be interpreted in context with morphology. In fact, in contrast with a general belief, they also lack absolute specificity. An eloquent example is represented by the rearrangement of the ALK gene that can occur in subsets of non-Hodgkin lymphoma, in pulmonary carcinoma, and in inflammatory myofibroblastic tumour. The commonest diagnostic applications of genetic testing in sarcoma are the following:
1. Challenging differential diagnosis (i.e. poorly differentiated round cell synovial sarcoma vs. Ewing sarcoma; dedifferentiated liposarcoma vs retroperitoneal leiomyosarcoma).
2. Onset at non-typical anatomical sites (i.e. visceral locations).
3. Discrepancies between morphological and immunophenotypic findings
Chromosome translocations do not represent the only diagnostically relevant genetic alterations. Detection of MDM2 amplification (or overexpression of the protein thereof) represents in fact a key tool in the recognition of well differentiated as well as of dedifferentiated liposarcoma. Other important examples of diagnostic application of molecular genetics are represented by the detection of mutations of the beta-catenin gene in desmoid fibromatosis. Several attempts have ben made to correlate genetic abnormalities with prognosis and prediction of the response to therapy. Available data are significantly controversial. The single positive exception is represented by gastrointestinal stromal tumors (GIST). Mutational analysis of the KIT and PDGRFA genes in GIST in fact provide key prognostic and predictive indications allowing the most accurate therapeutic decision-making.