Kinoshita Yoshiaki, Tanaka Sakura, Souzaki Ryota, Miyoshi Kina, Kohashi Kenichi, Oda Yoshinao, Nakatsura Tetsuya, Taguchi Tomoaki
Department of Pediatric Surgery, Kyushu University, Fukuoka, Japan.
Department of Anatomic Pathology, Kyushu University, Fukuoka, Japan.
Eur J Pediatr Surg. 2015 Feb;25(1):138-44. doi: 10.1055/s-0034-1393961. Epub 2014 Oct 26.
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.
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.
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.
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.
磷脂酰肌醇蛋白聚糖3（GPC3）是一种与细胞膜结合的细胞表面硫酸乙酰肝素蛋白聚糖，在成人恶性肿瘤中被称为癌胚蛋白。在日本，使用GPC3肽疫苗的临床试验已作为成人肝细胞癌的一种新的免疫疗法启动。为了研究GPC3免疫疗法用于小儿恶性肿瘤的可能性，我们评估了GPC3在小儿恶性肿瘤中的表达。
采用免疫组织化学方法，检测了159例小儿实体瘤中GPC3的表达，其中包括35例神经母细胞瘤、30例肾母细胞瘤、10例肝母细胞瘤、25例生殖细胞肿瘤、56例横纹肌肉瘤和3例其他肿瘤。此外，为了阐明胎儿至新生儿期的生理表达情况，对9例胎儿和21例新生儿的无任何肿瘤疾病受试者的尸检标本进行了评估。还采用夹心酶联免疫吸附测定法，对53名受试者的标本进行分析，检测血清GPC3水平。
组织学上，11例卵黄囊瘤患者中有10例（90.9%）GPC3表达率高，10例肝母细胞瘤患者中有6例（60.0%）GPC3表达率高。此外，30例肾母细胞瘤患者中有9例（30.0%）GPC3表达呈阳性，56例横纹肌肉瘤患者中有14例（25.0%）GPC3表达呈阳性。关于尸检标本，23例7个月以下的受试者中，大多数在肝脏（94.7%）和肾脏（81.8%）表现出阳性结果。2例卵黄囊瘤患者（100%）和8例肝母细胞瘤患者中的6例（75.0%）血清学显示阳性表达率高。关于血清GPC3水平按年龄的分布，10例1岁以下的受试者中有8例（80.0%）呈阳性结果，而43例1岁以上的受试者中只有16例（37.3%）呈阳性结果。
大多数肝母细胞瘤和卵黄囊瘤病例，以及部分其他肿瘤病例，在组织学或血清学上被发现表达GPC3。另一方面，GPC3在1岁以下的胎儿和新生儿期呈生理性表达。虽然需要更多的初步数据和经验，但GPC3检测呈阳性结果的1岁以上患者被认为是接受使用GPC3肽疫苗接种的新免疫疗法的合适候选者。
