SYT—SSX融合基因及其亚型在滑膜肉瘤发生发展中的作用及预后意义

The role of SYT - SSX fusion genes in the development of synovial sarcoma and their prognostic value

目的研究SYT—SSX融合基因及其亚型（SYT—SSX1和SYT—SSX2）在滑膜肉瘤中的表达情况，探讨它们在滑膜肉瘤发生发展中的作用，并评价其预后意义。方法筛选152例滑膜肉瘤组织标本（来自129例患者），提取石蜡包埋组织中的RNA，采用逆转录-聚合酶链反应（RT—PCR）检测SYT—SSX及其亚型的表达，并比较SYT—SSX1和SYT—SSX2的表达与临床病理参数及预后之间的关系。结果145例（95．4％）组织标本表达SYT—SSX融合基因，其中50例（34．5％）呈SYT—SSX1阳性，91例（62．8％）呈SYT—SSX2阳性，4例（2．8％）SYT—SSX1和SYT—SSX2均为阴性。在SYT—SSX1阳性型滑膜肉瘤中，双相型、细胞角蛋白（CK）阳性和上皮膜抗原（EMA）阳性的比例显著高于SYT—SSX2阳性型（P均〈0．05）。多因素生存分析显示，肿瘤直径≥5cm[相对危险度（RR）=2．325，P=0．027]、有低分化区域（RR=2．122，P=0．048）、出现转移（RR=2．205，P=0．032）和SYT—SSX1阳性（RR=2．775，P=0．008）是提示患者预后不良的独立因素。结论大多数中国滑膜肉瘤患者可能为SYT—SSX2阳性；SYT—SSX亚型可以作为评估滑膜肉瘤患者预后的一项重要因素，SYT—SSX1阳性提示预后不良；SYT—SSX1和SYT—SSX2可能通过对不同的靶基因或对同一些靶基因不同程度的影响，呈现出调控滑膜肉瘤上皮分化能力的差异。

Objective To investigate the expression and role of SYT-SSX fusion genes in the careinogesis of synovial sarcoma, and to evaluate their prognostic value as well. Methods RNA was extracted from 152 selected synovial sarcoma tissue blocks embedded in paraffin. The expression of SYT-SSX fusion genes was detected with RT-PCR method. The correlation of SYT-SSX1 and SYT-SSX2 expression with clinicopathologic parameters and survival rate were analyzed. Results SYT-SSX was positively detected in 145 specimens （95.4%） , 34.5% （50/145） of these in SYT-SSX1 and 62.8% （91/145） in SYT-SSX2, respectively. However, 2. 8% （4/145） were negative for SYT-SSX1 and SYT-SSX2. The positive rate of biphasic type, CK-positive and EMA-positive in SYT-SSXl-synovial sarcoma were significantly higher than that in SYT-SSX2-synovial sarcoma （ P 〈 0.05 ）. The multivariate analysis showed that the prognosis of patients with tumor diameter ≥ 5 cm （ RR = 2. 325, P = 0.027 ） , containing poor differentiation areas （RR = 2. 122,P = 0. 048 ） ）, with metastasis （ RR = 2. 205, P = 0. 032 ） and expressing SYT-SSX1 （RR = 2. 775, P = 0. 008 ） was poor. Conclusion Most of Chinese synovial sarcomas have expression of SYT-SSX2 protein. SYT-SSX type may be considered as an important prognostic factor for synovial sarcoma patient. The expression of SYT-SSX1 may suggest a poor prognosis. SYT-SSX1 and SYT- SSX2 show different ability to control the epithelial differentiation of synovial sarcoma precursor cells through affecting some different target genes or the same genes at different levels.