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目的: 观察N- 乙酰转移酶NAT10 蛋白在软组织肉瘤中的表达及与类型、分级的关系。方法: 通过原核表达NAT10 蛋白免疫制备特异性多克隆抗体, 并经免疫印迹鉴定; 以组织芯片- 免疫组化检测166 例软组织肉瘤和28 例良性肿瘤及瘤样病变中NAT10 蛋白的表达。结果: 制备多克隆抗体经Western 印迹鉴定与NAT10 具有特异结合性。免疫组化显示166 例软组织肉瘤中NAT10 蛋白阳性95 例, 阳性率为57%( 95/ 166) , 28 例良性肿瘤及瘤样病变中4 例阳性14%( 4/ 28) , 两者间有显著性差异( P< 0. 05) 。NAT10 表达的主要分布为: 滑膜肉瘤76%( 13/ 17) 、恶性纤维组织细胞瘤75%( 15/ 20) 、原始神经外胚叶瘤( PNET) 70%( 16/ 23) 、横纹肌肉瘤70%( 7/ 10) 、恶性外周神经鞘膜瘤50%( 11/ 22) 、隆突性皮肤纤维肉瘤50%( 7/ 14) 、平滑肌肉瘤43%( 6/ 14) 、脂肪肉瘤42%( 8/ 19) 、黏液性纤维肉瘤38%( 6/ 16) 。统计比较显示: 滑膜肉瘤与黏液性纤维肉瘤和脂肪肉瘤, 以及恶性纤维组织细胞瘤与黏液性纤维肉瘤之间NAT10 表达具有显著性差异( P< 0. 05) ; 而其它各组间无明显差异( P> 0. 05) 。同时, NAT10 蛋白强阳性表达( \+ + ) 多存在于滑膜肉瘤( 53%, 9/ 17) 、横纹肌肉瘤( 40%, 4/ 10) 及恶性纤维组织细胞瘤( 40%, 8/ 20) 。在FNCLCC 分级中,19 例I 级肉瘤中NAT10 阳性表达率为42% ( 8/ 19) , 44 例II 级肉瘤为43% ( 19/ 44) , 70 例III 级肉瘤为73% ( 51/ 70) 。III 级 NAT10 阳性率显著高于II 级组和I 级组( 均为P< 0. 05) 。结论: 研究表明N- 乙酰转移酶NAT10 表达于多种人软组织肉瘤, 尤其在高度恶性肉瘤, 因此有可能为软组织肉瘤的分级及预后因子。

英文摘要:

Objective: To evaluate the expression of N- acetyltransferase NAT10 protein in human tumors of soft tissue and its significance. Methods: Anti- NAT10 polyclonal antibody was generated by immunization of E. coli expressing NAT10 protein. The expression of NAT10 in 166 cases of soft- tissue sarcoma( STS) and 28 cases of benign tumors or tumor- like lesions of soft tissue arranged in tissue chip was analyzed by immunohistochemistry. Results: Polyclonal antibody obtained from immunized rabbit was verified its specific reactivity with native NAT10 protein by Western blot. The immunohistochemical staining of NAT10 showed that about 57% ( 95/ 166) of STS were positive and only 14%( 4/ 28) for benign tumors or tumor- like lesions, there was significant difference between STS and benign lesions. The positive distribution in NAT 10 expression was mainly synovial sarcoma 76% ( 13/ 17) , malignant fibrous histiocytoma 75%( 15/ 20) , rhabdomyosarcoma 70% ( 7/ 10) , primitive neuroectodermal tumor ( PNET) 70%( 16/ 23) , dermatofibrosarcoma protuberans 50%( 7/ 14) , malignant peripheral nerve sheath tumor 50%( 11/ 22) , leiomyosarcoma 43%( 6/ 14) , liposarcoma 42%( 8/ 19) and myxofibrosarcoma 38%( 6/ 16) . The statistical analysis showed that NAT10 expression of synovial sarcoma was different from those of myxofibrosarcoma or liposarcoma ( P< 0. 05) , and malignant fibrous histiocytoma from myxofibrosarcoma ( P< 0. 05) , but no differences in other groups( P> 0. 05) . Meanwhile, strong positive staining of NAT10 ( \+ + ) was much frequently in synovial sarcoma ( 53%, 9/ 17) , rhabdomyosarcoma 40%( 4/ 10) or malignant fibrous histiocytoma 40%( 8/ 20) . In FNCLCC grading, the positive expression rates of NAT10 were 42%( 8/ 19) in 19 cases of grade1 sarcoma, 43%( 19/ 44) in 44 cases of grade2, and 73%( 51/ 70) in 70 of grade3, which was significantly higher than those in grade 1 or 2 ( P< 0. 05) . Conclusions: NAT10 protein could be detected in many kinds of STS, especially in high histological grading, and thus it could be a potential factor for grading or prognosis of STS.

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