N- 乙酰转移酶NAT10 在软组织肿瘤中的表达及意义

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；以组织芯片一免疫组化检测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FNCLGC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。

Expression of human N- acetyltransferase 10(NAT10) protein in tumors of soft tissue and its significance

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.