Glypican 3 expression in tumors with loss of SMARCB1/INI1 protein expression.
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.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
Kenichi
K
Kohashi
Tetsuya
T
Nakatsura
Yoshiaki
Y
Kinoshita
Hidetaka
H
Yamamoto
Yuichi
Y
Yamada
Tatsuro
T
Tajiri
Tomoaki
T
Taguchi
Yukihide
Y
Iwamoto
Yoshinao
Y
Oda
D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D053673:Glypicans / Q000097:blood / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D018335:Rhabdoid Tumor / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein; D012509:Sarcoma / Q000175:diagnosis; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C105937:GPC3 protein, human; D053673:Glypicans; D012333:RNA, Messenger; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors