TEIF蛋白在软组织肉瘤中的表达及意义

目的 观察TEIF蛋白在软组织肉瘤组织中的表达及与类型、分级的关系。方法通过原核表达TEIF蛋白免疫制备多克隆抗体,免疫印迹鉴定。以组织芯片-免疫组织化学（En Vision法）检测166例软组织肉瘤和28例良性肿瘤及瘤样病变标本TEIF蛋白表达。结果制备多克隆抗体经Western印迹鉴定与TEIF具有特异结合性。免疫组织化学显示166例软组织肉瘤中TEIF蛋白阳性97例,阳性率为58％（97／166）,高于良性肿瘤及瘤样病变（11％,3／28）（P＜0．05）。阳性主要分布为：滑膜肉瘤94％（16／17）、原始神经外胚叶瘤（PNET）91％（21／23）,两者高于隆突性皮肤纤维肉瘤43％（6／14）、黏液性纤维肉瘤38％（6／16）、恶性外周神经鞘膜瘤36％（8／22）、脂肪肉瘤32％（6／19）（P＜0．05）,而与恶性纤维组织细胞瘤75％（15／20）、横纹肌肉瘤（7／10）、平滑肌肉瘤64％（9／14）差异无统计学意义（P〉0．05）。同时,TEIF蛋白的弥漫阳性表达（≥2＋）多存在于PNET和滑膜肉瘤,分别为83％（19／23）和76％（13／17）。在法国癌症中心联盟（FNCLCC）分级中,19例Ⅰ级肉瘤中TEIF阳性表达为32％（6／19）,44例Ⅱ级肉瘤阳性率为48％（21／44）,两者中2＋以上阳性分别为11％（2／19）、32％（14／44）,而70例Ⅲ级肉瘤中TEIF阳性表达为84％（59／70）和2＋以上阳性为70％（49／70）。Ⅲ级组的TEIF阳性率（及2＋以上阳性率）显著高于Ⅱ级组和Ⅰ级组（均为P＜0．05）,而后两者间则差异无统计学意义（P＞0．05）。结论 TEIF蛋白表达存在于软组织肉瘤,尤其高表达于PNET、滑膜肉瘤,并与肉瘤的组织学分级有关。

Expression of TEIF protein in soft tissue tumors and its significance

OBJECTIVE: To evaluate the expression of TEIF protein in human tumors of soft tissue and its significance. METHODS: Anti-TEIF polyclonal antibody was generated by immunization of E.coli expressed His-TEIF protein. The expression of TEIF in 166 cases of sarcomas and 28 case 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 in Western blot to prove its specific reactivity with native TEIF protein. The immunohistochemical staining of TEIF showed that about 58% (97/166) of sarcomas were positive and significantly different from that of benign tumors or tumor-like lesions (11%, 3/28). The positive staining was predominantly in synovial sarcoma 94% (16/17), primitive neuroectodermal tumor (PNET) 91% (21/23), both of which were significantly higher than 43% (6/14) of dermatofibrosarcoma protuberans, 38% (6/16) of myxofibrosarcoma, 36% (8/22) of malignant peripheral nerve sheath tumor, 32% (6/19) of liposarcoma, (P < 0.05, respectively), but not higher than 75% (15/20) of malignant fibrous histiocytoma, 70% (7/10) of rhabdomyosarcoma or 64% (9/14) of leiomyosarcoma. Meanwhile, strong positive staining of TEIF (>or= 2+) was frequently observed in PNET (83%, 19/23) and synovial sarcoma (76%, 13/17). With respect to FNCLCC grading, 19 cases of grade I sarcoma TEIF was 32% (6/19) and strong positive was 11% (2/19), 44 cases of grade II sarcoma was 48% (21/44) and 32% (14/44), and 70 of grade III was 84% (59/70) and 70% (49/70). The rate of either positive or strong positive in grade III sarcoma was significantly different from that of either grade I or II (P < 0.05), but no difference between the latter two groups (P > 0.05). CONCLUSIONS: TEIF protein could be detected in large part of soft tissue sarcomas, and it not only over-expressed in most of PNET, synovial sarcomas, but also correlated with histological grading.