Testicular Germ Cell Tumours - features and prospects of the novel tumour marker microRNA-371a-3p (M371 test): a narrative review

Testicular germ cell tumours (GCTs) represent a paradigm for the usefulness of serum tumour markers in clinical management of diseases. However, the tumour markers currently in use, beta human chorionic gonadotropin (bHCG), alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) are expressed in less than 50% of GCT cases. In 2011, microRNA-371a-3p (currently named M371) was suggested as a novel marker for the first time. Chemically, microRNAS represent small RNA molecules consisting of 18-24 base pairs. Physiologically, these microRNAs play a prominent role in the epigenetic control of protein biosynthesis. M371 can be measured in serum with PCR-techniques. There is high level evidence for a 90% sensitivity and >90% specificity for GCTs of the marker M371. That high diagnostic accuracy is true for both seminoma and nonseminoma but not for the histologic subgroup of teratoma. Testicular tumours of non-germ cell origin and malignant neoplasms of other organs do not express the marker. M371 involves a very short half-life of <24 hours. The test does likely involve the prospects of providing substantial aid in clinical decision-making with respect to instances where improvement of GCT management is still required. In particular, the following clinical scenarios will probably benefit from the employment of the M371 test: (1) diagnostic work-up of incidentally detected small testicular masses with decision-making in regard to testis sparing surgery or full orchiectomy (2) simplifying the follow-up of GCT patients with sparing of imaging procedures in a number of cases; (3) diagnostic evaluation of retroperitoneal lymphadenopathy upon clinical staging; (4) diagnostic evaluation of false-positive elevations of classical tumour markers (AFP, bHCG); (5) rapid appraisal of therapeutic success or failure by means of the very short half-life of M371; (6) diagnostic evaluation of postchemotherapy residual masses particularly those in seminoma patients. The discovery and development of the novel tumour marker M371 probably represents a milestone progress in the history of the clinical management of testicular GCTs.