Serum Levels of MicroRNA371a-3p: A Highly Sensitive Tool for Diagnosing and Staging Testicular Germ Cell Tumours: A Clinical Case Series

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.

Download Full-text

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

World Journal of Urology ◽

10.1007/s00345-021-03876-2 ◽

2021 ◽

Author(s):

Klaus-Peter Dieckmann ◽

Cansu Dumlupinar ◽

Arlo Radtke ◽

Cord Matthies ◽

Renate Pichler ◽

...

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Germ Cell ◽

Tumour Size ◽

Clinical Stage ◽

Serum Levels ◽

Germ Cell Tumours ◽

Testicular Germ Cell ◽

Testicular Germ Cell Tumours ◽

Stage 1

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.

Download Full-text

High Expression of microRNA-371a-3p in Cystic Fluid of Post-Chemotherapy Teratoma with Concurrent Normal Serum Levels in Patients with Non-Seminomatous Testicular Germ Cell Tumours

Urologia Internationalis ◽

10.1159/000510760 ◽

2020 ◽

pp. 1-6

Author(s):

Klaus-Peter Dieckmann ◽

Finja Hennig ◽

Petra Anheuser ◽

Ralf Gehrckens ◽

Florian Viehweger ◽

...

Keyword(s):

Germ Cell ◽

Drainage System ◽

Cystic Teratoma ◽

Serum Levels ◽

Retroperitoneal Lymph Node Dissection ◽

The Novel ◽

Germ Cell Tumours ◽

Testicular Germ Cell ◽

Cystic Fluid ◽

Testicular Germ Cell Tumours

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Download Full-text

The Potential of Artificial Intelligence to Detect Lymphovascular Invasion in Testicular Cancer

Cancers ◽

10.3390/cancers13061325 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1325

Author(s):

Abhisek Ghosh ◽

Korsuk Sirinukunwattana ◽

Nasullah Khalid Alham ◽

Lisa Browning ◽

Richard Colling ◽

...

Keyword(s):

Artificial Intelligence ◽

Testicular Cancer ◽

Germ Cell ◽

Lymphovascular Invasion ◽

Automatic Segmentation ◽

Prognostic Significance ◽

Germ Cell Tumours ◽

Testicular Germ Cell ◽

Testicular Germ Cell Tumours ◽

Whole Slide Images

Testicular cancer is the most common cancer in men aged from 15 to 34 years. Lymphovascular invasion refers to the presence of tumours within endothelial-lined lymphatic or vascular channels, and has been shown to have prognostic significance in testicular germ cell tumours. In non-seminomatous tumours, lymphovascular invasion is the most powerful prognostic factor for stage 1 disease. For the pathologist, searching multiple slides for lymphovascular invasion can be highly time-consuming. The aim of this retrospective study was to develop and assess an artificial intelligence algorithm that can identify areas suspicious for lymphovascular invasion in histological digital whole slide images. Areas of possible lymphovascular invasion were annotated in a total of 184 whole slide images of haematoxylin and eosin (H&E) stained tissue from 19 patients with testicular germ cell tumours, including a mixture of seminoma and non-seminomatous cases. Following consensus review by specialist uropathologists, we trained a deep learning classifier for automatic segmentation of areas suspicious for lymphovascular invasion. The classifier identified 34 areas within a validation set of 118 whole slide images from 10 patients, each of which was reviewed by three expert pathologists to form a majority consensus. The precision was 0.68 for areas which were considered to be appropriate to flag, and 0.56 for areas considered to be definite lymphovascular invasion. An artificial intelligence tool which highlights areas of possible lymphovascular invasion to reporting pathologists, who then make a final judgement on its presence or absence, has been demonstrated as feasible in this proof-of-concept study. Further development is required before clinical deployment.

Download Full-text