Glypican 3 overexpression in primary and metastatic Wilms tumors

Maria Tretiakova*, Debra L. Zynger, Chunyan Luan, Nicole K. Andeen, Laura S. Finn, Masha Kocherginsky, Bin T. Teh, Ximing J. Yang

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Glypican 3 (GPC3), a heparan sulfate proteoglycan, plays a role in cell growth and differentiation. Mutations of the GPC3 gene are responsible for Simpson-Golabi-Behmel syndrome, which is characterized by anomalies of postnatal overgrowth and an increased risk of developing pediatric malignancies, mostly Wilms tumor and liver cancer. In order to understand the possible role of GPC3 in renal development and Wilms tumor formation, we analyzed messenger RNA (mRNA) and protein levels of GPC3 in sporadic Wilms tumors and compared it to normal kidneys and other common renal epithelial tumors. By using Affymetrix HGU133 oligonucleotide gene expression microarray data from 191 renal tumors and 12 normal kidneys, we found significant overexpression of GPC3 in Wilms tumors (p < 0.01), with 3.5-fold higher expression in comparison to normal kidneys and 6.5-fold higher than any type of renal tumors. The GPC3 gene product in Wilms tumor was further evaluated by immunohistochemistry and quantified by an automated image analysis. Cytoplasmic and membranous GPC3 immunoreactivity was present in 77 % of primary Wilms tumors (23/30), 93 % of metastatic Wilms tumors (13/14), 50 % of metanephric adenomas (4/8), 33 % of congenital mesoblastic nephromas (2/6), 100 % of nephrogenic rests (11/11), and 100 % of fetal kidneys (5/5). GPC3 staining was predominantly identified in blastemal and epithelial components of Wilms tumors, similar to that of fetal non-neoplastic kidney. All adult renal tumors (n = 60) and normal kidneys (n = 15) were GPC3 negative. These findings suggest the utility of GPC3 in differential diagnosis and follow-up of Wilms tumors. Our data also indicate that GPC3 is an oncofetal protein with a potential therapeutic value.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
JournalVirchows Archiv
Volume466
Issue number1
DOIs
StatePublished - Feb 4 2015

Fingerprint

Glypicans
Wilms Tumor
Kidney
Neoplasms
Mesoblastic Nephroma
Heparan Sulfate Proteoglycans
Liver Neoplasms
Oligonucleotides
Adenoma
Genes
Cell Differentiation

Keywords

  • GPC3
  • Glypican 3
  • Wilms tumor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Tretiakova, Maria ; Zynger, Debra L. ; Luan, Chunyan ; Andeen, Nicole K. ; Finn, Laura S. ; Kocherginsky, Masha ; Teh, Bin T. ; Yang, Ximing J. / Glypican 3 overexpression in primary and metastatic Wilms tumors. In: Virchows Archiv. 2015 ; Vol. 466, No. 1. pp. 67-76.
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abstract = "Glypican 3 (GPC3), a heparan sulfate proteoglycan, plays a role in cell growth and differentiation. Mutations of the GPC3 gene are responsible for Simpson-Golabi-Behmel syndrome, which is characterized by anomalies of postnatal overgrowth and an increased risk of developing pediatric malignancies, mostly Wilms tumor and liver cancer. In order to understand the possible role of GPC3 in renal development and Wilms tumor formation, we analyzed messenger RNA (mRNA) and protein levels of GPC3 in sporadic Wilms tumors and compared it to normal kidneys and other common renal epithelial tumors. By using Affymetrix HGU133 oligonucleotide gene expression microarray data from 191 renal tumors and 12 normal kidneys, we found significant overexpression of GPC3 in Wilms tumors (p < 0.01), with 3.5-fold higher expression in comparison to normal kidneys and 6.5-fold higher than any type of renal tumors. The GPC3 gene product in Wilms tumor was further evaluated by immunohistochemistry and quantified by an automated image analysis. Cytoplasmic and membranous GPC3 immunoreactivity was present in 77 {\%} of primary Wilms tumors (23/30), 93 {\%} of metastatic Wilms tumors (13/14), 50 {\%} of metanephric adenomas (4/8), 33 {\%} of congenital mesoblastic nephromas (2/6), 100 {\%} of nephrogenic rests (11/11), and 100 {\%} of fetal kidneys (5/5). GPC3 staining was predominantly identified in blastemal and epithelial components of Wilms tumors, similar to that of fetal non-neoplastic kidney. All adult renal tumors (n = 60) and normal kidneys (n = 15) were GPC3 negative. These findings suggest the utility of GPC3 in differential diagnosis and follow-up of Wilms tumors. Our data also indicate that GPC3 is an oncofetal protein with a potential therapeutic value.",
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Tretiakova, M, Zynger, DL, Luan, C, Andeen, NK, Finn, LS, Kocherginsky, M, Teh, BT & Yang, XJ 2015, 'Glypican 3 overexpression in primary and metastatic Wilms tumors', Virchows Archiv, vol. 466, no. 1, pp. 67-76. https://doi.org/10.1007/s00428-014-1669-4

Glypican 3 overexpression in primary and metastatic Wilms tumors. / Tretiakova, Maria; Zynger, Debra L.; Luan, Chunyan; Andeen, Nicole K.; Finn, Laura S.; Kocherginsky, Masha; Teh, Bin T.; Yang, Ximing J.

In: Virchows Archiv, Vol. 466, No. 1, 04.02.2015, p. 67-76.

Research output: Contribution to journalArticle

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T1 - Glypican 3 overexpression in primary and metastatic Wilms tumors

AU - Tretiakova, Maria

AU - Zynger, Debra L.

AU - Luan, Chunyan

AU - Andeen, Nicole K.

AU - Finn, Laura S.

AU - Kocherginsky, Masha

AU - Teh, Bin T.

AU - Yang, Ximing J.

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