Testicular germ cell tumours of adolescents and adults
Evidence supports the derivation of testicular germ cell tumours from primordial germ cells or gonocytes. Testicular germ cell tumours are the most common solid malignancy in young adult Caucasian men with two histological subtypes, the seminomas and non seminomas. Although largely curable, long-term risks are associated with their treatment, including cardiovascular disease and secondary malignancies. Approximately 25-30% of patients with stage I nonseminoma will relapse from micrometastatic disease not detectable at presentation. In those with vascular invasion, the best current risk factor, this rises to 35-40% versus 15-20% when absent. We aim to identify better risk stratification for these patients.
We have shown that testicular germ cell tumours express the chemokine receptor CXCR4 and in models systems demonstrated migration of testicular germ cell tumours cells towards its ligand, CXCL12 (SDF1). This parallels our work on KIT and its ligand KITLG (SCF) in seminomas and is consistent with factors known to affect the migration of primordial germ cells during development. We are currently testing the hypothesis that lack of expression of the CXCL12 ligand in a subset of stage I non seminomas is associated with increased risk of relapse in a large series of samples from patients on clinical trials.
High and low immunohistochemistry positivity for CXCL12 (brown) in embryonal carcinoma cases of testicular germ cell tumours. Stronger staining was associated with reduced risk of relapse.
Soft Tissue Sarcomas
Soft tissue tumours are a heterogeneous group of mesenchymal tumours that frequently exhibit features of differentiating soft tissues such as striated skeletal muscle (known as rhabdomyosarcomas) and fat (liposarcomas).