TY - JOUR
T1 - Glypican 3 expression in tumors with loss of SMARCB1/INI1 protein expression
AU - Kohashi, Kenichi
AU - Nakatsura, Tetsuya
AU - Kinoshita, Yoshiaki
AU - Yamamoto, Hidetaka
AU - Yamada, Yuichi
AU - Tajiri, Tatsuro
AU - Taguchi, Tomoaki
AU - Iwamoto, Yukihide
AU - Oda, Yoshinao
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research (B) (No. 21390107) and Young Scientists (B) (No.21790356) from the Japan Society for the Promotion of Science, the National Cancer Center Research and Development Fund (23-B-12), and Health and Labor Science Research Grants for Clinical Research from the Ministry of Health, Labor and Welfare, Tokyo, Japan. The English used in this manuscript was revised by KN International ( http://www.kninter.com/ ).
PY - 2013/4
Y1 - 2013/4
N2 - Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies such as Wilms tumor. Malignant rhabdoid tumor (MRT), originally described as a rhabdomyosarcomatoid variant of Wilms tumor, is a tumor with loss of SMARCB1/INI1 protein expression. We analyzed the frequency of GPC3 protein expression, GPC3 mRNA, and serum-soluble GPC3 levels in 71 cases of tumors with loss of SMARCB1/INI1 protein expression, including 14 MRTs, 48 epithelioid sarcomas (ES) (proximal-type, 21; distal-type, 27), 4 extraskeletal myxoid chondrosarcomas, and 5 pediatric undifferentiated soft-tissue sarcomas. We found that GPC3 overexpression of more than 10% of the labeling index was recognized in 6 (42.9%) MRTs, 1 (2.1%) proximal-type ES, and 3 (60%) pediatric undifferentiated soft-tissue sarcomas (MRT vs ES, P =.0003). All the remaining cases revealed GPC3-absent expression of less than 1% of the labeling index. The median values of GPC3 mRNA in the GPC3-absent expression group and overexpression group were 10.2 and 309, respectively, with a statistically significant difference between these 2 groups (P =.004). However, there was no statistically significant difference in the prognoses of these 2 groups of MRT (P =.99). In analyzable cases of small-number MRT and pediatric undifferentiated soft-tissue sarcoma, there is no significant correlation between GPC3 immunoreactivity and serum-soluble GPC3 level. Therefore, evaluation of GPC3 immunoexpression may be a useful diagnostic tool to distinguish ES from MRT, especially extrarenal MRT. It was suggested that MRTs with GPC3 overexpression may become a new target of GPC3 immunotherapy.
AB - Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies such as Wilms tumor. Malignant rhabdoid tumor (MRT), originally described as a rhabdomyosarcomatoid variant of Wilms tumor, is a tumor with loss of SMARCB1/INI1 protein expression. We analyzed the frequency of GPC3 protein expression, GPC3 mRNA, and serum-soluble GPC3 levels in 71 cases of tumors with loss of SMARCB1/INI1 protein expression, including 14 MRTs, 48 epithelioid sarcomas (ES) (proximal-type, 21; distal-type, 27), 4 extraskeletal myxoid chondrosarcomas, and 5 pediatric undifferentiated soft-tissue sarcomas. We found that GPC3 overexpression of more than 10% of the labeling index was recognized in 6 (42.9%) MRTs, 1 (2.1%) proximal-type ES, and 3 (60%) pediatric undifferentiated soft-tissue sarcomas (MRT vs ES, P =.0003). All the remaining cases revealed GPC3-absent expression of less than 1% of the labeling index. The median values of GPC3 mRNA in the GPC3-absent expression group and overexpression group were 10.2 and 309, respectively, with a statistically significant difference between these 2 groups (P =.004). However, there was no statistically significant difference in the prognoses of these 2 groups of MRT (P =.99). In analyzable cases of small-number MRT and pediatric undifferentiated soft-tissue sarcoma, there is no significant correlation between GPC3 immunoreactivity and serum-soluble GPC3 level. Therefore, evaluation of GPC3 immunoexpression may be a useful diagnostic tool to distinguish ES from MRT, especially extrarenal MRT. It was suggested that MRTs with GPC3 overexpression may become a new target of GPC3 immunotherapy.
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U2 - 10.1016/j.humpath.2012.06.014
DO - 10.1016/j.humpath.2012.06.014
M3 - Article
C2 - 23084579
AN - SCOPUS:84875224097
SN - 0046-8177
VL - 44
SP - 526
EP - 533
JO - Human Pathology
JF - Human Pathology
IS - 4
ER -