Glypican 3 expression in pediatric malignant solid tumors

Yoshiaki Kinoshita, Sakura Tanaka, Ryota Sozaki, Kina Miyoshi, Kenichi Kouhashi, Yoshinao Oda, Tetsuya Nakatsura, Tomoaki Taguchi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose Glypican 3 (GPC3) is one of the cell surface heparan sulfate proteoglycans that binds to the cell membrane, and it is known as an oncofetal protein in adult malignant tumors. Clinical trials using a GPC3 peptide vaccine have already been started in Japan as a new immunotherapy for hepatocellular carcinoma in adult patients. To investigate the possibility of GPC3 immunotherapy for pediatric malignant tumors, we assessed the expression of GPC3 in pediatric malignant tumors. Methods Immunohistochemically, the GPC3 expression was examined in 159 pediatric solid tumors, including 35 cases of neuroblastoma, 30 cases of Wilms tumor, 10 cases of hepatoblastoma, 25 cases of germ cell tumors, 56 cases of rhabdomyosarcoma, and 3 cases of other tumors. In addition, to clarify the physiological expression during the fetal to neoinfantile period, autopsy specimens of subjects without any neoplastic diseases were assessed in 9 fetal cases and 21 neoinfantile cases. The serum levels of GPC3 were also analyzed using specimens obtained from 53 subjects by the sandwich enzyme-linked immunosorbent assay method. Results Histologically, a high rate of GPC3 expression was noted in 10 (90.9%) of the 11 subjects with yolk sac tumors and 6 (60.0%) of the 10 subjects with hepatoblastoma. In addition, 9 (30.0%) of the 30 subjects with Wilms tumors and 14 (25.0%) of the 56 subjects with rhabdomyosarcoma were positive for the expression of GPC3. Concerning autopsy specimens, most of the 23 subjects younger than 7 months showed positive findings in the liver (94.7%) and kidney (81.8%). Two subjects (100%) with yolk sac tumors and six (75.0%) of the eight subjects with hepatoblastoma serologically demonstrated a high rate of positive expression. Concerning the distribution of the serum GPC3 level according to age, 8 (80.0%) of the 10 subjects younger than 1 year showed a positive finding, while only 16 (37.3%) of the 43 subjects older than 1 year showed a positive finding. Conclusion Most cases of hepatoblastoma and yolk sac tumor, and some cases of other tumors were found to express GPC3 either histologically or serologically. On the other hand, GPC3 was physiologically expressed during the fetal and neoinfantile period under 1 year of age. Although, more preliminary data and experience are required, patients older than 1 year that show a positive finding for GPC3 are considered to be appropriate candidates to receive the new immunotherapy using GPC3 peptide vaccination.

Original languageEnglish
Pages (from-to)138-144
Number of pages7
JournalEuropean Journal of Pediatric Surgery
Volume25
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

Glypicans
Pediatrics
Neoplasms
Hepatoblastoma
Endodermal Sinus Tumor
Immunotherapy
Wilms Tumor
Rhabdomyosarcoma
Autopsy
Heparan Sulfate Proteoglycans
Subunit Vaccines
Germ Cell and Embryonal Neoplasms
Serum
Neuroblastoma

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Surgery

Cite this

Glypican 3 expression in pediatric malignant solid tumors. / Kinoshita, Yoshiaki; Tanaka, Sakura; Sozaki, Ryota; Miyoshi, Kina; Kouhashi, Kenichi; Oda, Yoshinao; Nakatsura, Tetsuya; Taguchi, Tomoaki.

In: European Journal of Pediatric Surgery, Vol. 25, No. 1, 2015, p. 138-144.

Research output: Contribution to journalArticle

Kinoshita, Yoshiaki ; Tanaka, Sakura ; Sozaki, Ryota ; Miyoshi, Kina ; Kouhashi, Kenichi ; Oda, Yoshinao ; Nakatsura, Tetsuya ; Taguchi, Tomoaki. / Glypican 3 expression in pediatric malignant solid tumors. In: European Journal of Pediatric Surgery. 2015 ; Vol. 25, No. 1. pp. 138-144.
@article{e7685beea5804805b77ed5442a51436d,
title = "Glypican 3 expression in pediatric malignant solid tumors",
abstract = "Purpose Glypican 3 (GPC3) is one of the cell surface heparan sulfate proteoglycans that binds to the cell membrane, and it is known as an oncofetal protein in adult malignant tumors. Clinical trials using a GPC3 peptide vaccine have already been started in Japan as a new immunotherapy for hepatocellular carcinoma in adult patients. To investigate the possibility of GPC3 immunotherapy for pediatric malignant tumors, we assessed the expression of GPC3 in pediatric malignant tumors. Methods Immunohistochemically, the GPC3 expression was examined in 159 pediatric solid tumors, including 35 cases of neuroblastoma, 30 cases of Wilms tumor, 10 cases of hepatoblastoma, 25 cases of germ cell tumors, 56 cases of rhabdomyosarcoma, and 3 cases of other tumors. In addition, to clarify the physiological expression during the fetal to neoinfantile period, autopsy specimens of subjects without any neoplastic diseases were assessed in 9 fetal cases and 21 neoinfantile cases. The serum levels of GPC3 were also analyzed using specimens obtained from 53 subjects by the sandwich enzyme-linked immunosorbent assay method. Results Histologically, a high rate of GPC3 expression was noted in 10 (90.9{\%}) of the 11 subjects with yolk sac tumors and 6 (60.0{\%}) of the 10 subjects with hepatoblastoma. In addition, 9 (30.0{\%}) of the 30 subjects with Wilms tumors and 14 (25.0{\%}) of the 56 subjects with rhabdomyosarcoma were positive for the expression of GPC3. Concerning autopsy specimens, most of the 23 subjects younger than 7 months showed positive findings in the liver (94.7{\%}) and kidney (81.8{\%}). Two subjects (100{\%}) with yolk sac tumors and six (75.0{\%}) of the eight subjects with hepatoblastoma serologically demonstrated a high rate of positive expression. Concerning the distribution of the serum GPC3 level according to age, 8 (80.0{\%}) of the 10 subjects younger than 1 year showed a positive finding, while only 16 (37.3{\%}) of the 43 subjects older than 1 year showed a positive finding. Conclusion Most cases of hepatoblastoma and yolk sac tumor, and some cases of other tumors were found to express GPC3 either histologically or serologically. On the other hand, GPC3 was physiologically expressed during the fetal and neoinfantile period under 1 year of age. Although, more preliminary data and experience are required, patients older than 1 year that show a positive finding for GPC3 are considered to be appropriate candidates to receive the new immunotherapy using GPC3 peptide vaccination.",
author = "Yoshiaki Kinoshita and Sakura Tanaka and Ryota Sozaki and Kina Miyoshi and Kenichi Kouhashi and Yoshinao Oda and Tetsuya Nakatsura and Tomoaki Taguchi",
year = "2015",
doi = "10.1055/s-0034-1393961",
language = "English",
volume = "25",
pages = "138--144",
journal = "European Journal of Pediatric Surgery",
issn = "0939-7248",
publisher = "Thieme Medical Publishers",
number = "1",

}

TY - JOUR

T1 - Glypican 3 expression in pediatric malignant solid tumors

AU - Kinoshita, Yoshiaki

AU - Tanaka, Sakura

AU - Sozaki, Ryota

AU - Miyoshi, Kina

AU - Kouhashi, Kenichi

AU - Oda, Yoshinao

AU - Nakatsura, Tetsuya

AU - Taguchi, Tomoaki

PY - 2015

Y1 - 2015

N2 - Purpose Glypican 3 (GPC3) is one of the cell surface heparan sulfate proteoglycans that binds to the cell membrane, and it is known as an oncofetal protein in adult malignant tumors. Clinical trials using a GPC3 peptide vaccine have already been started in Japan as a new immunotherapy for hepatocellular carcinoma in adult patients. To investigate the possibility of GPC3 immunotherapy for pediatric malignant tumors, we assessed the expression of GPC3 in pediatric malignant tumors. Methods Immunohistochemically, the GPC3 expression was examined in 159 pediatric solid tumors, including 35 cases of neuroblastoma, 30 cases of Wilms tumor, 10 cases of hepatoblastoma, 25 cases of germ cell tumors, 56 cases of rhabdomyosarcoma, and 3 cases of other tumors. In addition, to clarify the physiological expression during the fetal to neoinfantile period, autopsy specimens of subjects without any neoplastic diseases were assessed in 9 fetal cases and 21 neoinfantile cases. The serum levels of GPC3 were also analyzed using specimens obtained from 53 subjects by the sandwich enzyme-linked immunosorbent assay method. Results Histologically, a high rate of GPC3 expression was noted in 10 (90.9%) of the 11 subjects with yolk sac tumors and 6 (60.0%) of the 10 subjects with hepatoblastoma. In addition, 9 (30.0%) of the 30 subjects with Wilms tumors and 14 (25.0%) of the 56 subjects with rhabdomyosarcoma were positive for the expression of GPC3. Concerning autopsy specimens, most of the 23 subjects younger than 7 months showed positive findings in the liver (94.7%) and kidney (81.8%). Two subjects (100%) with yolk sac tumors and six (75.0%) of the eight subjects with hepatoblastoma serologically demonstrated a high rate of positive expression. Concerning the distribution of the serum GPC3 level according to age, 8 (80.0%) of the 10 subjects younger than 1 year showed a positive finding, while only 16 (37.3%) of the 43 subjects older than 1 year showed a positive finding. Conclusion Most cases of hepatoblastoma and yolk sac tumor, and some cases of other tumors were found to express GPC3 either histologically or serologically. On the other hand, GPC3 was physiologically expressed during the fetal and neoinfantile period under 1 year of age. Although, more preliminary data and experience are required, patients older than 1 year that show a positive finding for GPC3 are considered to be appropriate candidates to receive the new immunotherapy using GPC3 peptide vaccination.

AB - Purpose Glypican 3 (GPC3) is one of the cell surface heparan sulfate proteoglycans that binds to the cell membrane, and it is known as an oncofetal protein in adult malignant tumors. Clinical trials using a GPC3 peptide vaccine have already been started in Japan as a new immunotherapy for hepatocellular carcinoma in adult patients. To investigate the possibility of GPC3 immunotherapy for pediatric malignant tumors, we assessed the expression of GPC3 in pediatric malignant tumors. Methods Immunohistochemically, the GPC3 expression was examined in 159 pediatric solid tumors, including 35 cases of neuroblastoma, 30 cases of Wilms tumor, 10 cases of hepatoblastoma, 25 cases of germ cell tumors, 56 cases of rhabdomyosarcoma, and 3 cases of other tumors. In addition, to clarify the physiological expression during the fetal to neoinfantile period, autopsy specimens of subjects without any neoplastic diseases were assessed in 9 fetal cases and 21 neoinfantile cases. The serum levels of GPC3 were also analyzed using specimens obtained from 53 subjects by the sandwich enzyme-linked immunosorbent assay method. Results Histologically, a high rate of GPC3 expression was noted in 10 (90.9%) of the 11 subjects with yolk sac tumors and 6 (60.0%) of the 10 subjects with hepatoblastoma. In addition, 9 (30.0%) of the 30 subjects with Wilms tumors and 14 (25.0%) of the 56 subjects with rhabdomyosarcoma were positive for the expression of GPC3. Concerning autopsy specimens, most of the 23 subjects younger than 7 months showed positive findings in the liver (94.7%) and kidney (81.8%). Two subjects (100%) with yolk sac tumors and six (75.0%) of the eight subjects with hepatoblastoma serologically demonstrated a high rate of positive expression. Concerning the distribution of the serum GPC3 level according to age, 8 (80.0%) of the 10 subjects younger than 1 year showed a positive finding, while only 16 (37.3%) of the 43 subjects older than 1 year showed a positive finding. Conclusion Most cases of hepatoblastoma and yolk sac tumor, and some cases of other tumors were found to express GPC3 either histologically or serologically. On the other hand, GPC3 was physiologically expressed during the fetal and neoinfantile period under 1 year of age. Although, more preliminary data and experience are required, patients older than 1 year that show a positive finding for GPC3 are considered to be appropriate candidates to receive the new immunotherapy using GPC3 peptide vaccination.

UR - http://www.scopus.com/inward/record.url?scp=84964308664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964308664&partnerID=8YFLogxK

U2 - 10.1055/s-0034-1393961

DO - 10.1055/s-0034-1393961

M3 - Article

VL - 25

SP - 138

EP - 144

JO - European Journal of Pediatric Surgery

JF - European Journal of Pediatric Surgery

SN - 0939-7248

IS - 1

ER -