Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance
Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance
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DOI：
10.1016/j.humpath.2015.11.005
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发表时间：
2016-04-01
期刊：
影响因子：
3.3
通讯作者：
Nakayama, Jun
中科院分区：
文献类型：
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作者：
Momose, Takashige;Yoshimura, Yasuo;Nakayama, Jun
糖基转移酶硫酸软骨素合酶1（CHSY 1）和外生骨疣样3（EXTL 3）分别特异性地在聚糖硫酸软骨素和硫酸乙酰肝素的生物合成中起作用。虽然这些聚糖在各种肿瘤的发病机制中起重要作用，但它们在软组织肉瘤中的意义尚不清楚。在此，我们探讨CHSY 1或EXTL 3表达是否与软组织肉瘤粘液样物质的恶性潜能相关。为此，我们检查了40个代表特定类型的样本，包括12例粘液样脂肪肉瘤，14例粘液纤维肉瘤，12例恶性外周神经鞘瘤，2例低度纤维粘液样肉瘤。我们用抗CHSY 1和抗EXTL 3抗体进行免疫组化，并将酶表达水平与肿瘤组织学分级（由联邦国家癌症防治中心分类评估）和患者5年生存率进行比较。CHSY 1和EXTL 3分别在72.5%和32.5%的肿瘤中表达。值得注意的是，与其他肿瘤相比，CHSY 1在粘液纤维肉瘤和恶性外周神经鞘瘤中强表达，并且与高恶性肿瘤而不是低恶性肿瘤显著相关（P <0.01）。CHSY1的高表达也与较差的患者预后（P = 0.031）和美国癌症联合委员会分期系统评估的较高分期（P = 0.004）显著相关。相比之下，EXTL3表达与组织学分级或患者预后无关。我们的结论是，CHSY 1的表达与软组织肉瘤的恶性潜能与粘液物质密切相关。(C)2015爱思唯尔公司All rights reserved.
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 liposarconia, 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 Federation 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 loyer-gtade 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. (C) 2015 Elsevier Inc. All rights reserved.