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。
Objective: To evaluate the expression of N - acetyltransferase NAT10 protein in human tumors of soft tissue and its significance. Methods: Anti- NAT10 polydonal antibody was generated by immunization of E.coli expressing NAT10 protein. The expression of NAT10 in 166 cases of soft - tissue sarcoma(SIS) and 28 cases of benign tumors or tumor- like lesions of soft tissue arranged in tissue chip was analyzed by immunohistochcmistry. 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 SIS were positive and only 14%(4/28) for benign tumors or tumor- like lesions, there was significant difference between SIS 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 neuroectedermal tumor (PNET) 70%(16/23), dermatofibrosarcorua protuberans 50%(7/14), malignant peripheral nerve sheath tumor 50% ( 11/22), leiomyosareoma 43% (6/14), lipesareonm 42% (8/19) and myxofibrosarcorua 38% (6/16). The statistical analysis showed that NAT10 expression of synovial sarcoma was different from those dr myxofibrosarcoma or liposarcomaa (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 histioeytoma 40% (8/20). In FNCLCC grading, the positive expression rates of NAT10 were 42% (8/19) in 19 eases of gradel sarcoma, 43% (19/44) in 44 eases 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 ST