Clinicopathological implications ofGNASin Ewing sarcoma.
The objective of the present study was to determine whether guanine nucleotide-binding protein α stimulating (GNAS) gene expression correlates with pathognomonic signs by analyzing the mutations, methylation status and G-protein α subunit (Gsα) expression ofGNASin Ewing sarcoma (ES). Formalin-fixed paraffin-embedded tissue samples from 77 patients with primary ES were obtained in South Korea, Argentina and Brazil, and were studied via methylation chip assay and direct sequencing of theGNASgene and immunohistochemical analysis of Gsα. The mutation and methylation statuses of theGNASgene were examined. Immunohistochemical results were measured with respect to proportion and staining intensity. The results revealed thatGNASgenes in ES tumor samples were less methylated compared with normal controls. No mutations were detected at exons 8 or 9 of theGNASlocus complex on chromosome 20q13.3, indicating that the pathogenesis of ES was not associated withGNASmutation. Gsαexpression correlated well with the methylation status of theGNASgene. Notably, high Gsαexpression was detected more frequently in samples from living patients than from decedents, although this was not statistically significant (P=0.055). In conclusion,GNASmutation is not associated with the pathogenesis of ES tumors. This finding may be used to differentiate ES tumors from metastatic bone lesions with morphological similarity to ES tumors. Analysis of the methylation status of theGNASgene and immunohistochemical Gsαexpression suggests that hypermethylatedGNAS(low Gsαexpression) in ES may be associated with unfavorable progression with a non-significant trend.
Department of Pathology, School of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea.
Byeong-Joo
BJ
Noh
Department of Pathology, School of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea.
Ji-Youn
JY
Sung
Department of Pathology, School of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea.
Youn Wha
YW
Kim
Laboratory of Orthopedic Pathology, Central Army Hospital, Buenos Aires C1426BOR, Argentina.
Eduardo Santini
ES
Araujo
Molecular Pathology Division, SARAH Network of Rehabilitation Hospitals, Brasilia 70335-901, Brazil.
Ricardo Karam
RK
Kalil
Department of Biomedical Laboratory Science, College of Health Science, Korea University, Seoul 02708, Republic of Korea.
Woon-Won
WW
Jung
Department of Biomedical Laboratory Science, College of Health Sciences, Cheongju University, Chungcheongbuk 28503 Republic of Korea.
Hyun-Sook
HS
Kim
Department of Pathology, School of Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea.
Yong-Koo
YK
Park
Ewing sarcoma; GNAS