TY - JOUR
T1 - E-cadherin gene mutations frequently occur in synovial sarcoma as a determinant of histological features
AU - Saito, T.
AU - Oda, Y.
AU - Sugimachi, K.
AU - Kawaguchi, K. I.
AU - Tamiya, S.
AU - Tanaka, K.
AU - Matsuda, S.
AU - Sakamoto, A.
AU - Iwamoto, Y.
AU - Tsuneyoshi, M.
N1 - Funding Information:
Supported in part by a Grant-in-Aid for Cancer Research from the Fukuoka Cancer Society and a Grant-in-Aid for General Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (grant no. 12670167 ).
PY - 2001
Y1 - 2001
N2 - Synovial sarcoma is a mesenchymal tumor that has an epithelial character and two major histological sub-types, the biphasic type and the monophasic fibrous type. However, the mechanisms involved in its epithelial differentiation are unknown, and further more, the determinants for histological subtype in synovial sarcoma remain unclear. In this study, we immunohistochemicaUy examined E-cadherin expression and screened for genetic alterations in the E-cadherin gene from exon 4 to exon 9 in 49 cases of synovial sarcoma. In addition, we also examined the mRNA expressions of E-cadherin and Snail, a direct repressor of E-cadherin gene expression, by reverse transcriptase-polymerase chain reaction in 20 samples of frozen material. Immunohistochemical E-cadherin membranous expression was observed in 12 cases (24.5%), and was predominant in biphasic tumors. Single-strand conformation polymorphism analysis followed by DNA direct sequencing revealed 15 missense E-cadherin mutations in 12 cases (24.5%: Monophasic, 11 of 42; biphasic, 1 of 6; poorly, 0 of 1) and 7 silent mutations (14.3%) in 7 cases. Ten of the 12 cases with E-cadherin missense mutations did not show E-cadherin membranous expression. Reverse transcriptase-polymerase chain reaction demonstrated E-cadherin and Snail mRNA expressions in 14 cases (70%) and in all cases, respectively. E-cadherin gene expression was inactivated by missense mutations in three of the eight cases (37.5%) of monophasic fibrous tumors that showed E-cadherin mRNA expressions. The E-cadherin gene was potentially inactivated in a significant number of synovial sarcomas. E-cadherin dysfunction because of its mutation in the central region of the molecule was associated with its decreased immunohistochemical expression and histological fibroblastic and spindle-shaped features of monophasic tumors. Thus, E-cadherin gene mutation may be one of the determinants of histological subtype in synovial sarcoma.
AB - Synovial sarcoma is a mesenchymal tumor that has an epithelial character and two major histological sub-types, the biphasic type and the monophasic fibrous type. However, the mechanisms involved in its epithelial differentiation are unknown, and further more, the determinants for histological subtype in synovial sarcoma remain unclear. In this study, we immunohistochemicaUy examined E-cadherin expression and screened for genetic alterations in the E-cadherin gene from exon 4 to exon 9 in 49 cases of synovial sarcoma. In addition, we also examined the mRNA expressions of E-cadherin and Snail, a direct repressor of E-cadherin gene expression, by reverse transcriptase-polymerase chain reaction in 20 samples of frozen material. Immunohistochemical E-cadherin membranous expression was observed in 12 cases (24.5%), and was predominant in biphasic tumors. Single-strand conformation polymorphism analysis followed by DNA direct sequencing revealed 15 missense E-cadherin mutations in 12 cases (24.5%: Monophasic, 11 of 42; biphasic, 1 of 6; poorly, 0 of 1) and 7 silent mutations (14.3%) in 7 cases. Ten of the 12 cases with E-cadherin missense mutations did not show E-cadherin membranous expression. Reverse transcriptase-polymerase chain reaction demonstrated E-cadherin and Snail mRNA expressions in 14 cases (70%) and in all cases, respectively. E-cadherin gene expression was inactivated by missense mutations in three of the eight cases (37.5%) of monophasic fibrous tumors that showed E-cadherin mRNA expressions. The E-cadherin gene was potentially inactivated in a significant number of synovial sarcomas. E-cadherin dysfunction because of its mutation in the central region of the molecule was associated with its decreased immunohistochemical expression and histological fibroblastic and spindle-shaped features of monophasic tumors. Thus, E-cadherin gene mutation may be one of the determinants of histological subtype in synovial sarcoma.
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U2 - 10.1016/S0002-9440(10)63063-5
DO - 10.1016/S0002-9440(10)63063-5
M3 - Article
C2 - 11733362
AN - SCOPUS:0035180628
SN - 0002-9440
VL - 159
SP - 2117
EP - 2124
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -