Associations of serum levels of microRNA-371a-3p (M371) with risk factors for progression in nonseminomatous testicular germ cell tumours clinical stage 1

Klaus-Peter Dieckmann,Christian Wülfing,Friedemann Zengerling,Jörg Sommer,Arlo Radtke,Alexander Winter,Finja Hennig,Renate Pichler,Cord Matthies,Cansu Dumlupinar,Pia Paffenholz,Gazanfer Belge

doi:10.1007/s00345-021-03876-2

Abstract

PurposeLymphovascular invasion (LV1) and presence of > 50% embryonal carcinoma (> 50% EC) represent risk factors for progression in patients with clinical stage 1 (CS1) nonseminomatous (NS) testicular germ cell tumours. As serum levels of microRNA-371a-3p (M371) are capable of detecting small amounts of GCT, we evaluated if LV1 and > 50% EC are associated with M371 levels.MethodsM371 serum levels were measured postoperatively in 153 NS CS1 patients and both pre- and postoperatively in 131 patients. We registered the following factors: age, tumour size, LV status, > 50% EC, teratoma in primary, preoperative elevation of classical tumour markers. M371 expression was compared among subgroups. The ability of M371 to predict LV1 was calculated by receiver operating characteristics (ROC) curves. Multiple regression analysis was used to look for associations of M371 levels with other factors.ResultsPostoperatively elevated M371 levels were found in 29.4% of the patients, but were neither associated with LV status nor with > 50% EC. Likewise, relative decrease of M371 was not associated. ROC analysis of postoperative M371 levels revealed an AUC of 0.5 for the ability to predict LV1 while preoperative M371 had an AUC of 0.732. Multiple regression analysis revealed significant associations of preoperative M371 levels with LV status (p = 0.003), tumour size (p = 0.001), > 50% EC (p = 0.004), and teratoma component (p = 0.045).ConclusionPostoperatively elevated M371 levels are not associated with risk factors for progression in NS CS1 patients. However, the significant association of preoperative M371 expression with LV1 deserves further evaluation.

Highlights

Clinical stage 1 (CS1) nonseminomatous tumours (NS) comprise of 20% of all patients with testicular germ cell tumours (GCTs) [1]
Postoperative M371 levels are not associated with the LV status as shown by an AUC of 0.5 in the receiver operating characteristics (ROC) curve (Fig. 2b)
There is no association of postoperatively elevated M371 levels with the LV status

Summary

Introduction

Clinical stage 1 (CS1) nonseminomatous tumours (NS) comprise of 20% of all patients with testicular germ cell tumours (GCTs) [1]. Lymphovascular invasion (LV1, characterised as pathological stage pT2 according to the TNM classification) is the most widely recognised risk factor that indicates a 50–60% risk of developing metastases if no treatment is administered [9] Another promising risk marker is the presence of embryonal carcinoma (EC) in the primary tumour [10]. Lymphovascular invasion involves low specificity, since 15–20% of CS1 NS patients will progress despite the absence of vascular invasion (LVo) and about 40–50% with the factor (LV1) will not Another problem of histology-based risk factors is inter-observer variation in the assessment of testicular pathological details which relates to the over-all rarity of testicular neoplasms [12, 13]

Results

Discussion

Conclusion