Abstract
PurposeDiagnosing germ cell neoplasia in situ (GCNis) can detect germ cell tumours (GCTs) at the pre-invasive stage. To date, testicular biopsy with the potential of surgical complications is the only way of safely diagnosing GCNis. Recently, microRNAs (miRs) 371-3, and miR 367 were shown to be valuable serum biomarkers of GCTs. We explored the usefulness of these candidate miRs as a marker for GCNis.Methods27 patients with GCNis and no concomitant GCT were enrolled. All patients underwent measuring serum levels of miR-371a-3p and miR-367-3p before treatment, 11 had repeat measurement after treatment, 2 also had testicular vein blood examinations. Serum levels were measured by quantitative PCR. In addition, four orchiectomy specimens of patients with GCT were examined immunohistochemically and by in situ hybridization (ISH) with a probe specific for miR-371a-3p to look for the presence of this miR in GCNis cells.ResultsThe median serum level of miR-371a-3p was significantly higher in patients with GCNis than in controls, miR-367 levels were not elevated. Overall, 14 patients (51.9%) had elevated serum levels of miR-371a-3p. The highest levels were found in patients with bilateral GCNis. Levels in testicular vein serum were elevated in both of the cases. After treatment, all elevated levels dropped to normal. In two orchiectomy specimens, miR-371a-3p was detected by ISH in GCNis cells.ConclusionsMeasuring miR-371a-3p serum levels can replace control biopsies after treatment of GCNis. In addition, the test can guide clinical decision making regarding the need of testicular biopsy in cases suspicious of GCNis.
Highlights
Germ cell neoplasia in situ (GCNis; formerly called carcinoma in situ testis, CIS, or testicular intraepithelial1 3 Vol.:(0123456789)J Cancer Res Clin Oncol (2017) 143:2383–2392 neoplasia, TIN) is the uniform precursor of all adult testicular germ cell tumours (GCTs) (Rajpert-De Meyts et al 2016)
The median serum level of miR-371a-3p was significantly higher in patients with germ cell neoplasia in situ (GCNis) than in controls, miR-367 levels were not elevated
The test can guide clinical decision making regarding the need of testicular biopsy in cases suspicious of GCNis
Summary
J Cancer Res Clin Oncol (2017) 143:2383–2392 neoplasia, TIN) is the uniform precursor of all adult testicular germ cell tumours (GCTs) (Rajpert-De Meyts et al 2016). GCNis is thought to develop from embryonic germ cells and is present in the testis many years before the clinical manifestation of the GCT (Dieckmann and Skakkebaek 1999). Diagnosing GCNis represents a method of early detection of GCT at the pre-invasive stage. The diagnostic accuracy of semen-based examinations (Hoei-Hansen et al 2007a, b; van Casteren et al 2008a, b; Almstrup et al 2011) and imaging procedures (Lenz et al 1996; Holm et al 2001; Tsili et al 2013), proved to be unfavourably low, so far
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