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.

1.
Lange
PH
,
Winfield
HN
.
Biological markers in urologic cancer
.
Cancer
.
1987
;
60
(
3 Suppl
):
464
72
.
2.
Leão
R
,
Ahmad
AE
,
Hamilton
RJ
.
Testicular cancer biomarkers: a role for precision medicine in testicular cancer
.
Clin Genitourin Cancer
.
2018
;
17
:
e176
83
.
3.
Murray
MJ
,
Huddart
RA
,
Coleman
N
.
The present and future of serum diagnostic tests for testicular germ cell tumours
.
Nat Rev Urol
.
2016
;
13
(
12
):
715
25
.
4.
Dieckmann
KP
,
Simonsen-Richter
H
,
Kulejewski
M
,
Anheuser
P
,
Zecha
H
,
Isbarn
H
,
.
Serum tumour markers in testicular germ cell tumours: frequencies of elevated levels and extents of marker elevation are significantly associated with clinical parameters and with response to treatment
.
Biomed Res Int
.
2019
;
2019
:
5030349
.http://dx.doi.org/10.1155/2019/5030349.
PMID: 31275973
5.
Ockhuizen
T
,
Veenstra
J
,
Suurmeijer
AJ
,
Fleuren
GJ
,
Schraffordt Koops
H
,
de Bruijn
HW
,
.
Protein composition of cyst fluids from mature teratoma in patients with nonseminomatous germ cell tumors of the testis
.
Cancer
.
1985
;
56
(
9
):
2264
8
.
6.
Sella
A
,
el Naggar
A
,
Ro
JY
,
Dexeus
FH
,
Amato
RJ
,
Lee
JS
,
.
Evidence of malignant features in histologically mature teratoma
.
J Urol
.
1991
;
146
(
4
):
1025
8
.
7.
Hölzel
C
,
Weissbach
L
,
Mann
K
.
Prognostische Bedeutung von Tumormarkern in Zystenpunktaten fortgeschrittener Keimzelltumoren nach Chemotherapie
.
Aktuel Urol
.
1997
;
28
(
5
):
260
2
.
8.
Beck
SD
,
Patel
MI
,
Sheinfeld
J
.
Tumor marker levels in post-chemotherapy cystic masses: clinical implications for patients with germ cell tumors
.
J Urol
.
2004
;
171
(
1
):
168
71
.
9.
Almstrup
K
,
Lobo
J
,
Mørup
N
,
Belge
G
,
Rajpert-De Meyts
E
,
Looijenga
LHJ
,
.
Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours
.
Nat Rev Urol
.
2020
;
17
(
4
):
201
13
.
10.
Regouc
M
,
Belge
G
,
Lorch
A
,
Dieckmann
K-P
,
Pichler
M
.
Non-coding microRNAs as novel potential tumor markers in testicular cancer
.
Cancers
.
2020
;
12
(
3
):
749
.
11.
Belge
G
,
Hennig
F
,
Dumlupinar
C
,
Grobelny
F
,
Junker
K
,
Radtke
A
,
.
Graded expression of microRNA-371a-3p in tumor tissues, contralateral testes, and in serum of patients with testicular germ cell tumor
.
Oncotarget
.
2020
;
11
(
16
):
1462
73
.
12.
Lobo
J
,
Gillis
AJM
,
Jerónimo
C
,
Henrique
R
,
Looijenga
LHJ
.
Human germ cell tumors are developmental cancers: impact of epigenetics on pathobiology and clinic
.
Int J Mol Sci
.
2019
;
20
(
2
):
258
.
13.
Dieckmann
KP
,
Radtke
A
,
Geczi
L
,
Matthies
C
,
Anheuser
P
,
Eckardt
U
,
.
Serum levels of microRNA-371a-3p (M371 test) as a new biomarker of testicular germ cell-tumors: results of a prospective multicentric study
.
J Clin Oncol
.
2019
;
37
:
1412
23
. .
14.
van Agthoven
T
,
Looijenga
LHJ
.
Accurate primary germ cell cancer diagnosis using serum based microRNA detection (ampTSmiR test)
.
Oncotarget
.
2017
;
8
(
35
):
58037
49
.
15.
Lobo
J
,
Gillis
AJM
,
van den Berg
A
,
Dorssers
LCJ
,
Belge
G
,
Dieckmann
K-P
,
.
Identification and validation model for informative liquid biopsy-based microRNA biomarkers: insights from germ cell tumor in vitro, in vivo and patient-derived data
.
Cells
.
2019
;
8
(
12
):
1637
.
16.
Leão
R
,
van Agthoven
T
,
Figueiredo
A
,
Jewett
MAS
,
Fadaak
K
,
Sweet
J
,
.
Serum miRNA predicts viable disease after chemotherapy in patients with testicular nonseminoma germ cell tumor
.
J Urol
.
2018
.
200
(
1
):
126
35
.
17.
Rosas Plaza
X
,
van Agthoven
T
,
Meijer
C
,
van Vugt
MATM
,
de Jong
S
,
Gietema
JA
,
.
miR-371a-3p, miR-373-3p and miR-367-3p as serum biomarkers in metastatic testicular germ cell cancers before, during and after chemotherapy
.
Cells
.
2019
;
8
(
10
):
1221
.
18.
Spiekermann
M
,
Belge
G
,
Winter
N
,
Ikogho
R
,
Balks
T
,
Bullerdiek
J
,
.
MicroRNA miR-371a-3p in serum of patients with germ cell tumours: evaluations for establishing a serum biomarker
.
Andrology
.
2015
;
3
(
1
):
78
84
.
19.
Livak
KJ
,
Schmittgen
TD
.
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method
.
Methods
.
2001
;
25
(
4
):
402
8
.
20.
Dieckmann
KP
,
Spiekermann
M
,
Balks
T
,
Ikogho
R
,
Anheuser
P
,
Wosniok
W
,
.
MicroRNA miR-371a-3p: a novel serum biomarker of testicular germ cell tumors: evidence for specificity from measurements in testicular vein blood and in neoplastic hydrocele fluid
.
Urol int
.
2016
;
97
:
76
83
.
21.
Ong
TA
,
Winkler
MH
,
Savage
PM
,
Seckl
MJ
,
Christmas
TJ
.
Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumour markers: indications, histopathology and outcome
.
BJU Int
.
2008
;
102
(
2
):
198
202
.
22.
Vilela-Salgueiro
B
,
Barros-Silva
D
,
Lobo
J
,
Costa
AL
,
Guimarães
R
,
Cantante
M
,
.
Germ cell tumour subtypes display differential expression of microRNA371a-3p
.
Philos Trans R Soc Lond B Biol Sci
.
2018
;
373
(
1748
):
20170338
.
23.
Radtke
A
,
Hennig
F
,
Ikogho
R
,
Hammel
J
,
Anheuser
P
,
Wülfing
C
,
.
The novel biomarker of germ cell tumours, micro-RNA-371a-3p, has a very rapid decay in patients with clinical stage 1
.
Urol Int
.
2018
;
100
(
4
):
470
5
.
24.
Mego
M
,
van Agthoven
T
,
Gronesova
P
,
Chovanec
M
,
Miskovska
V
,
Mardiak
J
,
.
Clinical utility of plasma miR-371a-3p in germ cell tumors
.
J Cell Mol Med
.
2019
;
23
(
2
):
1128
36
.
25.
Boellaard
WPA
,
Gillis
AJM
,
van Leenders
GJLH
,
Stoop
H
,
van Agthoven
T
,
Dorssers
LCJ
,
.
Cellular origin of microRNA-371a-3p in healthy males based on systematic urogenital tract tissue evaluation
.
Andrology
.
2019
;
7
(
4
):
463
8
.
26.
Murray
MJ
,
Bell
E
,
Raby
KL
,
Rijlaarsdam
MA
,
Gillis
AJ
,
Looijenga
LH
,
.
A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours
.
Br J Cancer
.
2015
;
114
(
2
):
151
62
.
27.
Nappi
L
,
Thi
M
,
Lum
A
,
Huntsman
D
,
Eigl
BJ
,
Martin
C
,
.
Developing a highly specific biomarker for germ cell malignancies: plasma miR371 expression across the germ cell malignancy spectrum
.
J Clin Oncol
.
2019
;
37
(
33
):
3090
8
.
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