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目的通过检测DNA拓扑异构酶Ⅱα(TopoⅡα)、细胞核相关抗原-67(Ki-67)的表达水平,评价子宫肉瘤细胞增殖的生物学行为,寻找其预后相关因素。方法回顾性分析解放军总医院因子宫肉瘤行肿瘤切除手术的患者48例。按照国际妇产科联盟(FIGO)分期标准,分为Ⅰ期22例,Ⅱ期12例,Ⅲ期8例,Ⅳ期6例。按照美国妇科肿瘤组(GOG)病理组织学分类,包括子宫平滑肌肉瘤(LMS)19例,子宫内膜间质肉瘤(ESS)21例,子宫恶性中胚叶混合瘤(MMMT)8例。应用免疫组织化学(IHC)方法检测TopoⅡα、Ki-67在子宫肉瘤中的表达水平并分析其与子宫肉瘤预后的相关性。结果TopoⅡα和Ki-67的高增殖(LI)组(阳性表达细胞数>25%)患者的2年、5年生存率与低LI组(阳性表达细胞数≤25%)患者比较均无明显差别,但总体生存率高LI组均明显低于低LI组(分别为P=0.002,P=0.004)。TopoⅡα和ki-67低LI组患者的复发包块体积均大于高LI组(P=0.005,P=0.000),且复发时间均明显长于高LI组(P=0.000,P=0.000)。TopoⅡα与Ki-67表达呈明显正相关(r=0.9355,P=0.000)。COX多因素分析表明,除病理类型及分期外,TopoⅡα和Ki-67的表达与患病年龄、初潮年龄、孕产次、月经周期及经期、是否绝经均无关。结论TopoⅡα与Ki-67均可作为细胞增殖的特异性标记物,但TopoⅡα在反映细胞精确的增殖状态方面较Ki-67可能有更好的特异性,结合病理类型及分期,可能对判断子宫肉瘤的预后具有重要指导意义。
Objective To evaluate the biological behavior of uterine sarcoma cell proliferation by detecting the expression of TopoⅡα and Ki-67, and to find out the prognostic factors. Methods A retrospective analysis of PLA General Hospital of uterine sarcoma resection of the tumor in 48 patients. According to the International Union of Gynecology and Obstetrics (FIGO) staging criteria, divided into 22 cases of stage I, 12 cases of stage II, 8 cases of stage III, 6 cases of stage IV. According to the American Gynecologic Oncology Group (GOG) histopathological classification, including 19 cases of uterine leiomyosarcoma (LMS), 21 cases of endometrial stromal sarcoma (ESS), 8 cases of uterine malignant mesodermal mixed tumor (MMMT). The expression of TopoⅡα and Ki-67 in uterine sarcoma was detected by immunohistochemistry (IHC) and the correlation between TopoⅡα and Ki-67 in uterine sarcoma was analyzed. Results The 2-year, 5-year survival rates of patients with hyperinflammatory (LI) group (> 25%) in TopoⅡα and Ki-67 groups were not significantly different from those in patients with low LI group (≤25% , But the overall survival rate was significantly lower in the LI group than in the low LI group (P = 0.002, P = 0.004, respectively). The volume of relapsed masses in TopoⅡα and ki-67 low LI patients were significantly larger than those in the high LI group (P = 0.005, P = 0.000), and the recurrence time was significantly longer than those in the high LI group (P = 0.000, P = 0.000). There was a significant positive correlation between TopoⅡα and Ki-67 (r = 0.9355, P = 0.000). Cox multivariate analysis showed that, in addition to pathological types and staging, Topo Ⅱ α and Ki-67 expression and age of illness, menarche age, pregnancy, menstrual cycle and menstrual period, whether menopause are not related. Conclusion Both TopoⅡα and Ki-67 can be used as specific markers of cell proliferation. However, TopoⅡα may be more specific than Ki-67 in reflecting the precise proliferation status of cells. Combined with pathological types and stages, TopoⅡα may play an important role in judging uterine sarcoma The prognosis is of great guiding significance.