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.