title: The present and future of serum diagnostic tests for testicular germ cell tumours.
abstract: Testicular germ cell tumours (GCTs) are the most common malignancy occurring in young adult men and the incidence of these tumours is increasing. Current research priorities in this field include improving overall survival for patients classified as being 'poor-risk' and reducing late effects of treatment for patients classified as 'good-risk'. Testicular GCTs are broadly classified into seminomas and nonseminomatous GCTs (NSGCTs). The conventional serum protein tumour markers α-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and lactate dehydrogenase (LDH) show some utility in the management of testicular malignant GCT. However, AFP and hCG display limited sensitivity and specificity, being indicative of yolk sac tumour (AFP) and choriocarcinoma or syncytiotrophoblast (hCG) subtypes. Furthermore, LDH is a very nonspecific biomarker. Consequently, seminomas and NSGCTs comprising a pure embryonal carcinoma subtype are generally negative for these conventional markers. As a result, novel universal biomarkers for testicular malignant GCTs are required. MicroRNAs are short, non-protein-coding RNAs that show much general promise as biomarkers. MicroRNAs from two 'clusters', miR-371-373 and miR-302-367, are overexpressed in all malignant GCTs, regardless of age (adult or paediatric), site (gonadal or extragonadal) and subtype (seminomas, yolk sac tumours or embryonal carcinomas). A panel of four circulating microRNAs from these two clusters (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p) is highly sensitive and specific for the diagnosis of malignant GCT, including seminoma and embryonal carcinoma. In the future, circulating microRNAs might be useful in diagnosis, disease monitoring and prognostication of malignant testicular GCTs, which might also reduce reliance on serial CT scanning. For translation into clinical practice, important practical considerations now need addressing.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.|Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Murray
authors.affiliation: The Institute of Cancer Research, Downs Road, Sutton, Surrey, SM2 5PT, UK.|The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Huddart
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.|Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Coleman
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006063:Chorionic Gonadotropin / Q000097:blood; D003955:Diagnostic Tests, Routine / Q000639:trends*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000097:blood; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood* / Q000473:pathology; D011379:Prognosis; D012680:Sensitivity and Specificity; D013736:Testicular Neoplasms / Q000097:blood* / Q000473:pathology; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D035683:MicroRNAs; D000509:alpha-Fetoproteins; D007770:L-Lactate Dehydrogenase