2022, Volume 38, Number 2, Page(s) 083-089
Role of Immunohistochemistry in the Differential Diagnosis of Pediatric Renal Tumors: Expression of Cyclin D1, Beta-Catenin , PDGFR-Alpha, and PTEN
Nuray KEPIL1, Şebnem BATUR1, Zeynep Ecem KAIN1, Gamze ÖZCAN1, Şenol EMRE2, Rahşan ÖZCAN2, Tülin Tiraje CELKAN3, Nil ÇOMUNOĞLU1
1Department of Pathology, Istanbul University, Cerrahpasa Faculty of Medicine, ISTANBUL, TURKEY
2Department of Pediatric Surgery, Istanbul University, Cerrahpasa Faculty of Medicine, ISTANBUL, TURKEY
3Department of Pediatrics Oncology, Liv Hospital, ISTANBUL, TURKEY
Keywords: Cyclin D1, Immunohistochemistry, Pediatric pathology, Renal tumors, Wilms tumor
Pediatric renal tumors overlap histomorphologically and may cause misdiagnosis. We aimed to determine the role of
immunohistochemical staining of Cyclin D1, PTEN, beta-catenin and PDGFR-alpha on pediatric renal tumors.
Material and Method: Thirty-six cases of 8 different tumors were included in the study. Four blocks of paraffin tissue microarray were
constructed. Cyclin D1, PTEN, beta-catenin and PDGFR-alpha were used in all cases. Staining intensity and extent were graded.
Results: All cases of clear cell sarcoma (CCS) and epithelial components of Wilms tumor (WT) showed immunopositivity for Cyclin D1 but
blastemal and stromal components of WT were negative. All cases of CCS and most cases of WT consisting of blastemal and stromal components
demonstrated loss of expression with PTEN.
Conclusion: Cyclin D1 is not a specific immunohistochemical marker due to its strong and diffuse positivity in CCS cases. It may be useful to
differentiate CCS from blastemal and stromal components of WT. Other markers except cyclin D1 do not have a role in the differential diagnosis.
Wilms tumor (WT) is the most common genitourinary
tumor of the children aged between 2-4 years. Having
triphasic components, which are blastemal, epithelial, and
stromal, it should be taken into the differential diagnosis
with other renal tumors. Clear cell sarcoma (CCS) is one
of the mesenchymal tumors of kidney, which is frequently
seen in the third year of life. Histologically, epithelioid cells
with round to oval nucleus form nests and cords. Malignant
rhabdoid tumor of kidney is a prominently aggressive
tumor, seen among children under 10 years. It is composed
of rhabdoid cells that have eosinophilic nucleolus and
cytoplasm, big round nucleus, and paranuclear inclusions.
These cells are epithelioid, round, and polygonal in
appearance and show a solid and trabecular growth pattern
. Mesoblastic nephroma, classified into two groups as
classical and cellular, is one of the mesenchymal tumors
with low potential of malignancy and is seen among
children younger than 3 years. Histologically, tumor cells
form fascicles composed of spindle cells and may resemble
Although clinical and radiological findings may be
helpful in differential diagnosis, all of the morphological
findings of renal pediatric tumors may overlap with the
various subtypes of Wilms tumor 2,3. Bi- or triphasic
Wilms tumor diagnosis might be mistaken with other
pediatric renal tumors in tru-cut biopsy materials as well
as monophasic Wilms tumor in nephrectomy materials.
Wilms tumor which has only pure blastemal component
may be confused with Ewing sarcoma and neuroblastoma;
components showing rhabdoid differentiation may be
confused with malignant rhabdoid tumor; and the stromal
component may be confused with clear cell sarcoma and
mesonephric nephroma. The stroma of Wilms tumor may
be in similar appearance to renal clear cell sarcoma (CCS),
particularly after pre-operative chemotherapy 3,4.
Cyclin D1, PTEN, Beta-catenin, and PDGF-alpha are the
pathways that play a role in pathogenesis of these tumors
mentioned above. Thus, the immunohistochemical work-up
may help to differentiate tumors with a similar appearance.
Recently, the YWHAE-FAM22 rearrangement, which is
shown in high grade endometrial stromal sarcoma, was
reported in CCS cases and this rearrangement was resulted
in upregulation of Cyclin D1. This immunohistochemical marker is recommended for differential diagnosis of
tumors resembling CCSs 3,5,6.
MicroRNA is present in various biological processes
such as growth, development, and metabolism. It was
shown that microRNA has a substantial role in the
pathogenesis of renal diseases. Above all, its solid role in
the progression of Wilms tumor was demonstrated. Some
studies depicted that dysregulation of microRNAs starts
activation of phosphatase and tensin homologue (PTEN)
/ phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)
signaling pathway. It was shown that this pathway plays a
role in the pathogenesis of Wilms tumor; PTEN positivity
positively correlated with the clinical stage and negatively
correlated with metastasis to lymph nodes 7,8.
The signalling pathway of WNT/beta-catenin has a role in
processes such as embryonic growth, tumorogenesis, cell
proliferation, differentiation, migration, and apoptosis.
Wilms tumors protein is a transcription factor that is
negatively correlated with the WNT/beta-catenin pathway.
Several studies have shown that the signaling pathway of
WNT/beta-catenin is activated in Wilms tumor 9,10.
PDGF is an angiogenic factor which is formed of PDGF-A
and B chains and is coded by 2 different genes. PDGF was
produced in the normal kidney and Wilms tumor cells
in vitro. Studies on Wilms tumor have indicated that the
PDGF-A and PDGF-alpha receptors are expressed in the
epithelial component 11.
In our study, we evaluated the staining features of
immunohistochemical markers, such as Cyclin D1, PTEN,
Beta-catenin, PDGFR-alfa, in morphologically overlapping
tumors and compared our results with recent articles.
The surgical pathology database of the Department of
Pathology, Istanbul University - Cerrahpasa Faculty of
Medicine was searched for pediatric renal tumors between
the years of 2000 and 2018. A total of 36 cases of 16 WT
(all cases were post-chemotherapy resections), 10 CCS,
3 cellular mesoblastic nephroma (CeMN), 2 classical
mesoblastic nephroma (CMN), 2 malignant rhabdoid
tumor, one Ewing sarcoma, one diffuse large B-cell
lymphoma (DLBCL), and one malignant solitary fibrous
tumor (MSFT), were included in the study. All cases were
diagnosed by one pediatric and one renal pathologist.
Verbal informed consent was obtained from the patients.
All tissues were fixed in 10% formalin and embedded in
paraffin. Four tumor tissue microarrays (TMA) blocks
were constructed, containing representative 4-micron thick sections, and processed as previously described 12.
Each component of Wilms tumor was sampled on TMA
blocks. Deparaffinization was performed using solutions
and they were rehydrated using a series of decreasing
alcohol concentrations. Samples were kept in 10 mmol/L
buffered citrate solution for 30 minutes at 36 °C. PTEN
(Roche, SP218), Beta-catenin (Roche, 14), PDFGR-alpha
(Thermo Scientific, Ab-1), Cyclin D1 (Roche, SP4-R)
immunohistochemical markers were employed with an
automatic device (BenchMark XT IHK/ISH Staining
Module, Ventana Medical Systems Ins., Medical Systems,
Tucson, AZ, USA), according to the manufacturers
instructions. Staining intensity was graded as weak (+),
moderate (++), or strong (+++) whereas the extent of
staining was graded according to the percentage. Nonstaining
and weak staining below 5% were considered to
All data have been presented as mean or median or in
numbers and percentages. Statistical comparisons and tests
for survival analyses were not performed due to the low
number of subjects.
The mean age of the 10 CCS cases was 12.5 (1-53 years) and
the female/male ratio was 3/7. The mean age of the 16 WT
cases was 5.18 (1-15 years) and the female/male ratio was
9/7. The mean age of the mesoblastic nephroma cases was 19
months (9 months - 3 years) and the female/male ratio was
2/1. The mean age of the classical/congenital mesoblastic
nephroma cases was 2 and both patients were male. The
mean age of the 2 malignant rhabdoid tumor cases was 18
months (12 months - 2 years) and the female/male ratio was
1/1. The Ewing sarcoma patient was female and 36 years
old. The diffuse large B-cell lymphoma patient was female
and 8 years old. The malignant solitary fibrous tumor
patient was male and 4 years old. The immunohistemical
staining features are summarized in the Table I
All 10 CCS cases stained with Cyclin D-1. Staining extent
varied between 10-90% (Figure 1A). The intensity of
staining was weak (+) to strong (+++). Seven out of 11
WT cases containing an epithelial component stained
moderately with an extent of 10-20%. Fourteen cases
that had a blastemal component (Figure 1B) and all 16
WT cases containing a stromal component (Figure 1C)
showed immunonegativity. Two of the 3 CeMN cases
were not stained, and the remaining one showed moderate
staining with an extent of 40% (Figure 1D). This case was re-evaluated on H&E slides. Morphological features of the
cells and the expansive growth pattern led us to consider it
as clear cell sarcoma.
Click Here to Zoom
|Figure 1: Cyclin D1 staining
features. A) Clear cell sarcoma
(x200), B) WT-Blastemal
component (x400), C) WTStromal
D) Cellular mesoblastic
Two CMN and two malignant rhabdoid tumor cases
showed immunonegativity. One Ewing sarcoma, one
MSFT, and the DLBCL cases were not stained.
A cytoplasmic staining pattern was considered as positive.
Three of the 10 CCS cases were negative, and 7 cases
showed weak to moderate staining with a extent of 30-
80% (Figure 2A). Among the 16 WT cases, all 11 cases
consisting of an epithelial component showed cytoplasmic,
weak to moderate immunopositivity with an extent of 40-
80%. One of the 14 cases with a blastemal component was
negative and the remaining cases showed weak-moderate
staining with 10-80% extent (Figure 2B). Out of the 16
Wilms tumor containing a stromal component, one case
showing rhabdoid features stained strongly with an extent
of 80%. Four of the cases were negative. The remaining
cases showed weak to moderate staining with 10-80%
extent. One Ewing sarcoma and one DLBCL were negative.
Two CMN cases were negative. Three CeMN cases showed
moderate staining with 60-80% extent. Two malignant
rhabdoid tumor cases showed weak to moderate staining
with an extent of 10-60%. One MSFT case showed strong
staining with 90% extent.
Click Here to Zoom
|Figure 2: Beta-catenin staining features. A) clear cell sarcoma
(x200), B) WT-Blastemal component (x400).
All 10 CCS cases were negative with PTEN. Among 16
Wilms tumors, 11 cases that had an epithelial component
showed weak staining with 100% extent, one case containing
blastemal component was negative, and the remaining cases
showed weak staining with an extent of 100%. One of the
16 cases that contained a stromal component was negative
and 5 showed moderate staining with 30-100% extent; two
of these 5 cases were composed of rhabdoid areas. The WT
case showing negativity in the blastemal component was
Stage 3, and the WT case showing negativity in stromal
component was Stage 2. Other cases stained weakly with an
extend of 100%. One of the two cases showing anaplasia in
stromal cells had weak staining with 100% extent and the
other was negative.
All three CeMN cases showed weak positivity with an
extent of 100%. Two congenital/classical type mesoblastic
nephroma cases were negative. Two malignant rhabdoid
tumor and one MSFT case stained weakly with 100%
extent. One Ewing sarcoma was negative. One DLBCL
showed moderate staining with an extent of 100%.
One of the 10 CCS cases was negative, and 9 cases showed
weak to moderate staining with an extent of 20-100%
(Figure 3). In two out of 11 cases with epithelial components,
the PDGFR stain could not be evaluated due to technical
reasons. The remaining 9 cases showed weak to moderate
staining with 40-80% extent. Twelve cases with a blastemal
component stained weak to moderate, with an extent of
30-80%. Two cases with rhabdoid features were negative.
In fourteen cases containing stromal components, weak
staining was observed with an extent of 20-80%.
Three CeMN cases showed weak to moderate staining
with an extent of 50-90%. One Ewing sarcoma and 2 CMN
cases were negative. Two malignant rhabdoid tumor cases
showed weak to moderate staining with 10-60% extent. One
case of MSFT showed moderate staining with an extent of
80%. One case of DLBCL showed moderate staining with
an extent of 90%.
Wilms tumor, clear cell sarcoma, atypical teratoid
rhabdoid tumor, and mesoblastic nephroma are pediatric
renal tumors and less frequently Ewing sarcoma has been
reported in this localization. We investigated the role of
these immunohistochemical markers in the differential
Although there are studies suggesting that immunohistochemical
markers can be helpful in these tumors, immunohistochemistry
is limited in the differential diagnosis
2,3. Cyclin D-1 as an immunohistochemical marker that
has been studied in pediatric renal tumors and has recently
been proposed as a sensitive marker for clear cell sarcomas
3,5-6,13. Jet Aw et al., Mirkovic et al., and Uddin et
al. reported immunopositivity in their CCS series with 8,
14, and 19 cases respectively 3,6,13. In our study, immunopositivity
with cyclin D-1 was observed in all 10 CCS
In the study of Jet Aw et al., cyclin D-1 was immunonegative
in the blastemal and stromal components of 8 Wilms
tumors, whereas the epithelial components showed
immunopositivity 13. Mirkovic et al. reported focal
positivity in the blastemal component in 18 out of 20 WT
cases. The epithelial component showed immunopositivity
in most of these cases. Uddin et al. reported that one of
the 9 WT cases showed weak positivity in the blastemal
component and 7 were positive in the epithelial component
3. In our study, staining intensity was weak to strong with
10-90% of extent in the epithelial components. Blastemal
and stromal components were negative.
The dysregulated genes of the G1-S phase of the cell cycle in
Wilms tumor have been reported previously. This finding
explains the cyclin D-1 immunexpression in the epithelial
component of Wilms tumors 14. Staining of blastemal
and stromal component was not observed in the Wilms
tumor in most studies, that is compatible with ours. Cyclin
D1 may be recommended as an immunohistochemical
marker in the differential diagnosis of CCS and Wilms
Morphologically, the classic mesoblastic nephroma consists
of a uniform, fibromatosis-like proliferation of
fusiform cells with a fascicular appearance and it might be
confused with the stromal component of Wilms tumor,
and CCS. Jet Aw et al., Mirkovic et al., and Uddin et al. have
reported Cyclin D-1 positivity in classical mesonephric
blastoma cases 3,6,13. In our study, 2 out of 5 mesoblastic
nephroma cases were classical and 3 of them were cellular.
Only one of these CeMN cases showed diffuse nuclear
positivity with Cyclin D-1. Cyclin D-1 is not a helpful
immunohistochemical marker in the differential diagnosis
of CCS with mesoblastic nephromas as there are varying
rates of positivity and negativity reported.
Jet Aw et al. reported patchy immunopositivity in their
6-case series, Mirkovic et al. reported focal positivity in 4
rhabdoid tumor cases, and Uddin et al. reported moderate
staining in 3 of their 4 cases 3,6,13. In our study, cyclin
D-1 was negative in 2 malignant rhabdoid tumors. Due
to the variable staining characteristics of Cyclin D1 in
malignant rhabdoid tumors, it cannot be recommended
as an immunohistochemical marker in the differential
While cyclin D-1 showed diffuse and strong immunopositivity
in 3 of 5 Ewing sarcoma cases of Mirkovic et al.
and 3 of 4 cases of Uddin et al., one Ewing sarcoma was
immunonegative in our study 3,6. Since the number of
cases was limited and different staining characteristics
were reported in the literature, the role of Cyclin D-1 in the
differential diagnosis of Ewing sarcoma from other tumors
was not fully determined.
Studies have reported diffuse and strong staining with
cyclin D-1 in neuroblastoma cases 3,6,13. Neuroblastoma
cases were not included in our study because we could
not find any neuroblastoma cases located at the kidney in
our archive. However, in our study, negative staining with
Cyclin D-1 was detected in a malignant solitary fibrous
tumor and diffuse large B-cell lymphoma cases, which are
very rare in the kidney.
Cyclin D-1 is a useful immunohistochemical marker due
to its strong and diffuse positivity in renal CCS cases and it
might be used to differentiate CCS from the blastemal and
stromal component of Wilms tumor.
The catenin beta-1 (CTNNB1) gene encodes the protein of
beta-catenin and the mutation of this gene primarily affects
the WNT-signaling pathway. As a result, the protein of
beta-catenin is stabilized, and its transcription is increased.
The pathway of the aberrant WNT/beta-catenin leads to
developmental malformations and associated malignancies.
The pathway of WNT/beta-catenin is frequently activated
in Wilms tumors.
In the English literature, nuclear positivity has been
reported in blastemal and stromal components of Wilms
tumor 9,15. In our study, beta-catenin showed cytoplasmic
positivity in all stromal, blastemal and epithelial
components of WT cases. One case with rhabdoid areas
among the cases that had stromal components showed
strong immunopositivity with an extent of 80 %. Although
nuclear positivity was not detected in our cases, cytoplasmic
staining was shown, which means that WNT/beta-catenin
pathway might have been activated in Wilms tumors.
Besides, cytoplasmic immunopositivity was observed in 7
CCS cases. This signaling pathway has not been studied in
CCS cases before.
While beta-catenin was found to be negative in classical
mesoblastic nephroma, cytoplasmic positivity was detected
in the cellular type.
In contrast to our study, Demellawy et al. indicated that
their classical mesoblastic nephroma and mixed mesoblastic
nephroma cases showed cytoplasmic staining while the
cellular mesoblastic nephroma cases were immunonegative
We showed that 2 renal malignant rhabdoid tumors were
weak to moderate immunopositive with a staning percentage
of 10-60%. Contrary to our findings, Saito et al. reported
immunonegativity in 6 cases of malignant rhabdoid tumors
3 of which were located in kidney 17. In our study, Ewing
sarcoma and DLBCL cases were immunonegative.
Our findings suggested that this pathway is activated in
WT, CCS, CeMN and rhabdoid tumor. The use of immunohistochemistry
in the differential diagnosis is limited.
MicroRNAs (miRNAs) play a role in the development and
progression of cancer as an oncogene or tumor suppressor
gene. MiR-21 has been reported to show overexpression
in almost of all solid tumors studied and play a role in the
pathogenesis of renal diseases. MiR-21 regulates multiple
target genes, such as PTEN, negatively. PTEN, in particular,
suppresses oncogene signaling pathways. In their study on
41 cases of Wilms tumor, Cui et al. have reported a negative
correlation between MiR-21 and PTEN levels. Low PTEN
protein levels have been shown to correlate with a poor
prognosis and late clinical stage 8. Liu et al. have performed
PTEN immunohistochemistry on 46 WT cases and reported that the tumor did not show strong immunopositivity as
much as surrounding normal tissue 7.
In our study, we observed weak immunopositivity in the
blastemal and epithelial components of WT cases. In 5 of
16 cases with a stromal component, moderate positivity
was found with an extent of 30-100%. Negativity and
significant loss of expression was observed in the anaplastic
component. In the literature, loss of expression has been
generally associated with a poor prognosis in Wilms tumor.
According to our findings, negativity and significant loss of
expression in the areas of anaplasia might be related with a
In a study conducted by Little et al., the PTEN mutation
was evaluated by the PCR method and only 2 of 12 CCS
cases were found to be mutated 18. We observed
immunonegativity in all 10 CCS cases. To the best of our
knowledge, there is no other study on this subject amongst
the documented literature in English. In addition, negativity
was detected in our classical mesoblastic nephroma and
Ewing sarcoma cases. In order to determine an association
with the prognosis, immunohistochemical and molecular
studies should be performed in large case series in order to
show the association with prognosis.
PDGFR is an angiogenic factor and is encoded by two
different genes consisting of A and B chains. The receptor
tyrosine kinases, KIT, PDGFR alpha and EGFR, are
involved in cell growth and malignant transformation
and regulation. Overexpression of PDGFR alpha has been
identified in colon, breast, lung, ovarian, and pancreatic
Wetli et al. investigated exon 12,14 and 18 mutations by
sequence analysis in 209 Wilms tumor cases, and did not
detect the PDGFR alpha mutation; they concluded that
PDGFR alpha immunostaining was not reliable 19.
Epithelial, stromal, and blastemal components of the 16
WT cases of our study showed immunopositivity with
varying intensity and extent. Negativity was found only in
the rhabdoid component.
There are no studies in the literature regarding the PDGFRalpha
mechanism in renal tumors except WT. In our study,
9 cases of CCS, 3 CeMN, one rhabdoid tumor, MSFT and
DLBCL showed immunpositivity. Ewing sarcoma and
classic MN cases were negative.
The use of this immunohistochemical marker in the differential
diagnosis is limited, but the role of PDGFR-alpha in
the pathogenesis of renal tumors can be investigated.
Immunohistochemically, Cyclin D-1 can be used to
differentiate renal clear cell sarcoma from other renal
tumors. Loss of expression of PTEN might be associated
with a poor prognosis in Wilms tumors. Its role and efficacy
in the differential diagnosis with other renal tumors is
limited. Although the role of immunohistochemistry
is limited, the beta-catenin pathway is used in Wilms
tumor, CCS, CeMN, and RT. The use of PDGFR-alpha
as an immunohistochemical marker is limited, but its
mechanism in renal tumors has not been investigated yet.
This can be a subject for future studies.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors
Concept: NK, ŞB, Design: NÇ, Data collection or
processing: ZEK, GÖ, Analysis or Interpretation: ŞE, RÖ,
NK, ŞB, TTC, Literature search: ZEK, GÖ, Writing: ZEK,
GÖ, NK, ŞB, TTC, Approval: NÇ.
1) Salvatorelli L, Parenti R, Leone G, Musumeci G, Vasquez E,
Magro G. Wilms tumor 1 (WT1) protein: Diagnostic utility in
pediatric tumors. Acta Histochem. 2015;117:367-78.
2) Al-Hussain T, Ali A, Akhtar M. Wilms tumor: An update. Adv
Anat Pathol. 2014;21:166-73.
3) Mirkovic J, Calicchio M, Fletcher CD, Perez-Atayde AR. Diffuse
and strong cyclin D1 immunoreactivity in clear cell sarcoma of
the kidney. Histopathology. 2015;67:306-12.
4) Husain AN, Pysher TJ. The kidney and lower urinary tract.
In: Stocker JT, Dehner LP, Husain AN, edsitors. Stocker and
Dehners pediatric pathology. 3rd ed. Spain:Wolters Kluwer
Health Adis; 2012.818-9.
5) Aw SJ, Chang KTE. Clear cell sarcoma of the kidney. Arch Pathol
Lab Med. 2019;143:1022-6.
6) Uddin N, Minhas K, Abdul-Ghafar J, Ahmed A, Ahmad Z.
Expression of cyclin D1 in clear cell sarcoma of kidney. Is it
useful in differentiating it from its histological mimics? Diagn
7) Liu GL, Yang HJ, Liu B, Liu T. Effects of microRNA-19b on the
proliferation, apoptosis, and migration of Wilms Tumor cells
via the PTEN/PI3K/AKT signaling pathway. J Cell Biochem.
8) Cui M, Liu W, Zhang L, Guo F, Liu Y, Chen F, Liu T, Ma R,
Wu R. Over-Expression of miR-21 and Lower PTEN Levels in
Wilms Tumor with Aggressive Behavior. Tohoku J Exp Med.
9) Perotti D, Hohenstein P, Bongarzone I, Maschietto M, Weeks
M, Radice P, Pritchard-Jones K. Is Wilms tumor a candidate
neoplasia for treatment with WNT/β-catenin pathway
modulators? -A report from the renal tumors biology-driven
drug development workshop. Mol Cancer Ther. 2013;12:2619-
10) Schweigert A, Fischer C, Mayr D, von Schweinitz D, Kappler R,
Hubertus J. Activation of the Wnt/b-catenin pathway is common
in Wilms tumor, but rarely through b-catenin mutation and APC
promoter methylation. Pediatr Surg Int. 2016;32:1141-6.
11) Ghanem M, Nijman R, Safan M, van der Kwast T, Vansteenbrugge
G. Expression and prognostic value of platelet-derived growth
factor-AA and its receptor α in nephroblastoma. BJU Int.
12) Kononen J, Bubendorf L, Kallioniemi A, Bärlund M, Schraml P,
Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP.
Tissue microarrays for high-throughput molecular profiling of
tumor specimens. Nat Med. 1998;4:844-7.
13) Jet Aw S, Hong Kuick C, Hwee Yong M, Wen Quan Lian D,
Wang S, Liang Loh AH, Ling S, Lian Peh G, Yen Soh S, Pheng
Loh AH, Hoon Tan P, Tou En Chang K. Novel karyotypes and
cyclin D1 immunoreactivity in clear cell sarcoma of the kidney.
Pediatr Dev Pathol. 2015;18:297-304.
14) Rigolet M, Faussillon M, Baudry D, Junien C, Jeanpierre C.
Profiling of differential gene expression in Wilms tumor by
cDNA expression array. Pediatr Nephrol. 2001;16:1113-21.
15) Corbin M, de Reyniès A, Rickman DS, Berrebi D, Boccon-Gibod
L, Cohen-Gogo S, Fabre M, Jaubert F, Faussillon M, Yilmaz
F, Sarnacki S, Landman-Parker J, Patte C, Schleiermacher G,
Antignac C, Jeanpierre C. WNT/beta-catenin pathway activation
in Wilms tumors: A unifying mechanism with multiple entries?
Genes Chromosomes Cancer. 2009;48:816-27.
16) El Demellawy D, Cundiff CA, Nasr A, Ozolek JA, Elawabdeh N,
Caltharp SA, Masoudian P, Sullivan KJ, de Nanassy J, Shehata
BM. Congenital mesoblastic nephroma: A study of 19 cases
using immunohistochemistry and ETV6-NTRK3 fusion gene
rearrangement. Pathology. 2016;48:47-50.
17) Saito T, Oda Y, Itakura E, Shiratsuchi H, Kinoshita Y, Oshiro Y,
Tamiya S, Hachitanda Y, Iwamoto Y, Tsuneyoshi M. Expression
of intercellular adhesion molecules in epithelioid sarcoma and
malignant rhabdoid tumor. Pathol Int. 2001;51:532-42.
18) Little SE, Bax DA, Rodriguez-Pinilla M, Natrajan R, Messahel
B, Pritchard-Jones K, Vujanic GM, Reis-Filho JS, Jones C.
Multifaceted dysregulation of the epidermal growth factor
receptor pathway in clear cell sarcoma of the kidney. Clin Cancer
19) Wetli SC, Leuschner I, Harms D, Rufle A, Foerster A, Bihl M,
Graf N, Furtwaengler R, Paulussen M, Briner J, Aslanidis C,
Schmitz G, Tornillo L, Mihatsch MJ, Zlobec I, Bruder E. KIT,
PDGFRalpha and EGFR analysis in nephroblastoma. Virchows
Copyright © 2022 The Author(s). This is an open-access article published by the Federation of Turkish Pathology Societies under the terms of the Creative Commons Attribution License
that permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited. No use, distribution, or reproduction is permitted that does not comply with these terms.