70例骨肉瘤临床病理分析及其Notch亚型表达的预后意义  

Clinicopathological characteristics of osteosarcoma and prognostic significance of Notch receptors and ligands expression:analysis of 70 cases

作　　者：唐雪峰 曾英[2] 王亚丽 谭秋林 吕杨帆 郭乔楠 TANG Xuefeng;ZENG Ying;WANG Yali;TAN Qiulin;LYU Yangfan;GUO Qiaonan(Department of Pathology,Second Affiliated Hospital,Army Medical University (Third Military Medical University),Chongqing,400037;Department of Pathology,Institute of Surgery Research,Third Affiliated Hospital,Army Medical University (Third Military Medical University),Chongqing,400042,China)

机构地区：[1]陆军军医大学(第三军医大学)第二附属医院病理科,重庆400037 [2]陆军军医大学(第三军医大学)第三附属医院(野战外科研究所)病理科,重庆400042

出　　处：《第三军医大学学报》2019年第4期339-345,共7页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81672653);重庆市基础科学与前沿技术研究重点项目(CSTC2015jcyjBX0067)~~

摘　　要：目的探讨骨肉瘤的临床病理特征、Notch受体配体表达及其对预后的影响。方法收集2008-2015年陆军军医大学(第三军医大学)第二附属医院、陆军特色医学中心病理科70例骨肉瘤进行临床资料总结和组织学观察,并行Notch通路4个受体Notch 1～4和3个配体Jagged1、Jagged2、DLL4免疫组织化学染色。对54例病例行预后因素分析。结果 70例患者平均年龄25. 1岁,男女比例3∶2。95. 7%(67/70例)的患者就诊时处于临床Ⅱ～Ⅲ期。影像学表现显示:61例(87. 1%)存在骨质破坏,8例(11. 4%)髓腔累及,29例(41. 4%)骨皮质累及,28例(40%)有骨膜反应。组织病理学可见,40例(57. 1%)浸润性生长,70例肉瘤细胞和肿瘤性骨样组织。免疫组化结果显示:受体Notch4表达率最高,为91. 4%(64/70),其次分别为Notch1(87. 1%)、Notch3(68. 6%)、Notch2(33. 9%)。配体Jagged1、Jagged2、DLL4表达率分别为87. 1%(61/70)、84. 3%(59/70)、88. 6%(62/70)。42例患者(60%)接受了化疗,67例患者(95. 7%)进行了手术。54例有随访资料的患者平均生存时间41. 68个月。1、2年和5年生存率分别为87%、66%和30%。生存曲线比较示Enneking分期、术前化疗、Notch3表达与预后相关(P=0. 017),Cox比例风险回归模型分析Enneking分期、术前化疗、Notch3表达是独立预后因素。结论骨肉瘤5年生存率低,Enneking分期晚、未行术前化疗、Notch3表达的患者生存时间短。Objective To investigate the clinicopathological features of osteosarcoma and the prognostic significance of the expression of Notch receptors and ligands.Methods We retrospectively analyzed the clinical and histopathological data of 70 patients with osteosarcoma treated in the Second and Third Affiliated Hospitals of Army Medical University from 2008 to 2015.Immunohistochemical staining was used to examine the expressin levels of 4 Notch receptors( Notch1-4) and 3 Notch ligands( Jagged1,Jagged2 and DLL4) in the surgical specimens.The risk factors that affected the outcomes of the patients were analyzed in 54 cases.Results The patients had a mean age of 25.1 years with a male to female ratio of 3∶ 2,and 95.7% of the patients were in stage Ⅱ-Ⅲ.Imaging examinations revealed bone destruction in 61 cases( 87.1%),medullary cavity involvement in 8 cases( 11.4%) and bone cortex involvement in 29 cases( 41.4%);periosteal reaction was detected in 28 cases( 40%).Histopathologically,57.1% of patients( 40 cases) showed invasive growth of osteosarcoma,and all the patients had sarcoma cells and neoplastic osteoid tissues.Immunohistochemical analysis showed positive Notch1, Notch2, Notch3 and Notch4 expression in 87.1%( 61/70),33.9%( 23/70),68.6%( 48/70) and 91.4%( 64/70) of the patients,respectively with the last one of the highest;positive expression of Jagged1,Jagged2 and DLL4 were detected in 87.1%( 61/70),84.3%( 59/70) and 88.6%( 62/70) of the patients.Sixty percent of the patients( 42 cases) received chemotherapy,and 95.7% of the patients( 67 cases) underwent surgeries.The mean survival time of the 54 patients with full follow-up data was 41.68 months and their 1-,2-and 5-year survival rates were 87%,66% and 30%, respectively.Survival curre analysis showed thed Enneking stage,oreoperative chemotherapy and Notch 3 experssion were related with prognosis( P = 0.017).Cox regression analysis showed that Enneking stage,preoperative chemotherapy and Notch3 expression were independent prognostic factors in these patients.Co

关 键 词：骨肉瘤 临床病理 免疫组化 预后 NOTCH3 

分 类 号：R730.23[医药卫生—肿瘤] R730.7[医药卫生—临床医学]