Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance

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• 作者：Takashige Momose ; MD^a ; ^b ; Yasuo Yoshimura ; MD^b ; Satoru Harumiya ; PhD^a ; Ken'ichi Isobe ; MD^b ; Munehisa Kito ; MD^b ; Mana Fukushima ; MD^a ; Hiroyuki Kato ; MD^b ; Jun Nakayama ; MD^a ; ^{jnaka@shinshu-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Chondroitin sulfate ; CHSY1 ; EXTL3 ; Heparan sulfate ; Soft tissue sarcoma
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：50
• 期：Complete
• 页码：15-23
• 全文大小：1056 K

文摘

The glycosyltransferases chondroitin sulfate synthase 1 (CHSY1) and exostoses-like 3 (EXTL3) specifically function in biosynthesis of the glycans chondroitin sulfate and heparan sulfate, respectively. Although these glycans play important roles in pathogenesis of various tumors, their significance in soft tissue sarcoma remains unknown. Here, we asked whether CHSY1 or EXTL3 expression correlates with malignant potential of soft tissue sarcomas with myxoid substance. To do so, we examined 40 samples representing specific types, including 12 cases of myxoid liposarcoma, 14 of myxofibrosarcoma, 12 of malignant peripheral nerve sheath tumor, and 2 of low-grade fibromyxoid sarcoma. We performed immunohistochemistry with anti-CHSY1 and anti-EXTL3 antibodies and compared enzyme expression levels with tumor histologic grade as assessed by the Fédération Nationale des Centres de Lutte Contre le Cancer classification and with patient 5-year survival rate. CHSY1 and EXTL3 were expressed in 72.5% and 32.5% of all tumors, respectively. Notably, CHSY1 was strongly expressed in myxofibrosarcoma and malignant peripheral nerve sheath tumor compared with other tumors and significantly associated with higher- rather than lower-grade tumors (P < .01). High expression of CHSY1 was also significantly associated with poorer patient outcomes (P = .031) and higher stages assessed by American Joint Committee on Cancer staging system (P = .004). By contrast, EXTL3 expression was not correlated with histologic grade or patient prognosis. We conclude that CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance.