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

Author(s):  
Klaus-Peter Dieckmann ◽  
Cansu Dumlupinar ◽  
Arlo Radtke ◽  
Cord Matthies ◽  
Renate Pichler ◽  
...  

Abstract Purpose Lymphovascular 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. Methods M371 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. Results Postoperatively 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). Conclusion Postoperatively 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.

2019 ◽  
Vol 2019 ◽  
pp. 1-22 ◽  
Author(s):  
Klaus-Peter Dieckmann ◽  
Hanna Simonsen-Richter ◽  
Magdalena Kulejewski ◽  
Petra Anheuser ◽  
Henrik Zecha ◽  
...  

Introduction. Although serum tumor markers beta human chorionic gonadotropin (bHCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are well-established tools for the management of testicular germ cell tumours (GCTs), there are only few data from contemporary cohorts of primary GCT patients regarding these biomarkers. Our aim was to evaluate marker elevations in testicular GCTs and to document their associations with various clinical characteristics.Patients and Methods. A total of 422 consecutive patients with GCTs were retrospectively analysed regarding serum levels of bHCG, AFP, and LDH during the course of treatment. Additionally, the following characteristics were recorded: histology, age, laterality, clinical stage (CS), pT-stage, and tumour size. Marker elevations were first tabulated in dichotomized way (elevated: yes/no) in various subgroups and second as continuous measured serum values. Descriptive statistical methods were employed to look for differences among subgroups and for associations of elevations with clinical parameters.Results. In all GCT patients, the frequencies of elevated levels of bHCG, AFP, LDH, and bHCG or AFP were 37.9%, 25.6%, 32.9%, and 47.6%; in pure seminomas 28%, 2.8%, 29.1%, and 30.3%; and in nonseminoma 53.0%, 60.1%, 38.7%, and 73.8%. Significant associations were noted with pT-stages >pT1, clinical stages >CS1, tumour size, and younger age. Frequencies of marker elevations dropped significantly after treatment, but LDH levels remained elevated in 30.5%-34.1%. Relapsing patients (n=27) had elevated levels of bHCG, AFP, and LDH in 25.9%, 22.2%, and 29.6%, respectively, thirteen of whom with a changed marker pattern.Conclusions. The classical GCT-biomarkers correlate with treatment success. Clinical utility is limited due to proportions of < 50% of patients with elevated levels and the low specificity of LDH. The elevation rates are significantly associated with histology, clinical and pT-stages, tumour size, and younger age. Individual marker patterns may change upon relapse. Clinically, ideal biomarkers are yet to be found.


1989 ◽  
Vol 64 (3) ◽  
pp. 302-304 ◽  
Author(s):  
D. B. SMITH ◽  
E. S. NEWLANDS ◽  
G. J. S. RUSTIN ◽  
R. H. J. BEGENT ◽  
K. D. BAGSHAWE

2017 ◽  
Vol 99 (1) ◽  
pp. 98-103 ◽  
Author(s):  
Petra Anheuser ◽  
Arlo Radtke ◽  
Christian Wülfing ◽  
Jennifer Kranz ◽  
Gazanfer Belge ◽  
...  

Author(s):  
Christian Winter ◽  
Peter Albers

Testicular germ cell tumours (GCTs) represent the most common solid malignancy of young men aged 15–40 years. The disease is rising in incidence. Germ cell tumours are best divided into those with pure seminoma and non-seminoma (NSGCT) histology. While cryptorchidism is clearly established as a risk factor, the pathogenesis of testicular cancer remains unknown. Familial studies and molecular analyses suggest an association to genetic alterations. Most testicular cancer patients present a primary tumour in the testis. Diagnostic examinations include testis palpation and ultrasound, and measurement of serum tumour markers (AFP, ß-HCG, and LDH). Surgical exploration is obligatory for suspected tumours and radical orchidectomy should be performed if a tumour is found. Prognosis and subsequent treatment depends upon the clinical stage and the IGCCCG classification (in case of advanced GCT disease).


2020 ◽  
pp. 1-6
Author(s):  
Klaus-Peter Dieckmann ◽  
Finja Hennig ◽  
Petra Anheuser ◽  
Ralf Gehrckens ◽  
Florian Viehweger ◽  
...  

<b><i>Background:</i></b> MicroRNA-371a-3p (miR-371), the novel serum biomarker of testicular germ cell tumours (GCTs), is produced by undifferentiated subtypes of GCTs but not by teratoma. Cystic teratoma developing from retroperitoneal metastases of GCT subsequent to chemotherapy had been shown to contain high levels of classical serum tumour markers of GCT in the presence of normal marker levels in serum. To date, no information is available regarding the presence of miR-371 in the cystic fluid of residual teratoma after chemotherapy. <b><i>Methods:</i></b> Four patients (age 18–26 years) undergoing retroperitoneal lymph node dissection (RPLND) for cystic residual masses resulting from chemotherapy of bulky retroperitoneal GCT had measurements of miR-371 in both serum and cystic fluid aspirated from surgical specimens. Measurement of the miR was performed with quantitative real-time PCR using miR-30b-5p as reference. Results were tabulated and analysed in a descriptive manner. <b><i>Results:</i></b> Histologically, all of the surgical specimens involved teratoma only with no evidence of vital undifferentiated GCT tissue. All patients were cured. Prior to RPLND, miR-371 serum levels were not measurable or close to zero in all of the patients. Cystic fluid revealed elevated levels of miR-371 in 3 patients and traces of miR in one. <b><i>Conclusions:</i></b> The detection of miR-371 in the cystic fluid of teratoma is somewhat enigmatic since this GCT subtype usually does not express the miR. Two hypotheses may explain the finding: First, miR-371 molecules were released into the cystic fluid by active GCT tissue prior to chemotherapy. High levels were kept after regression of vital GCT tissue because the cystic lumen is without a specific drainage system. Second, teratoma cells lining the interior cyst wall may shed small amounts of miR-371 into the lumen. Because of the lacking drainage system, even small levels may accumulate. The present finding adds to the understanding of the biology of the novel biomarker of GCT.


Author(s):  
Gazanfer Belge ◽  
Francesca Grobelny ◽  
Arlo Radtke ◽  
Jacqueline Bodes ◽  
Cord Matthies ◽  
...  

Abstract Purpose Serum levels of microRNA-371a-3p (M371) have been shown to be a highly sensitive and specific biomarker for testicular germ cell tumours (TGCT). Little information exists on the expression of this marker in testicular neoplasms deriving from the gonadal stroma or other structures of the gonad. This study presents an expression analysis of the novel TGCT-biomarker M371 in a large cohort of testicular non-germ cell tumours. Methods The M371 expression was measured by quantitative real time PCR in serum of 99 patients with testicular tumours of non-germ cell origin, thereof 30 patients with malignant testicular lymphomas and 61 patients with gonadal stroma tumours such as Leydig cell tumours, Sertoli cell tumours and 8 cases with miscellaneous benign testicular tumours. Their M371 levels were compared to those of 20 patients with TGCT and to 37 tumour-free male controls. Results The median expression levels of benign testicular tumours and testicular lymphoma are close to zero, thus, identical with those of controls and significantly lower than those of TGCT. In summary, this study provides further evidence for the notion that M371 is exclusively expressed by germ cell tumours and not by testicular neoplasms of the non-germ cell subtypes. Conclusion Clinically, the test might be of value in preoperative characterization of benign testicular tumours eligible for conservative surgery.


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