VEGF-D在乳腺癌淋巴管生成中的作用及与预后的关系VoI.27No.11Nov2007上海交通大学(医学版)JournalofShanghai激aotongUniversity(MedicalScience)?l349?:0258～5898(2007)11—1349—05?-临床研究?VEGF-D在乳腺癌淋巴管生成中的作用及与预后的关系戚晓亮,顾岩,张瑞,郭善禹',夏永峰,何柳,汤亭亭,鲍泳扬(上海交通大学医学院第九人民医院1.普外科,2.骨科实验室,3.病理科,上海200011)摘要:目的探讨血管内皮生长因子D(VEGF—D)在乳腺癌淋巴管生成中的作用及其与临床病理指标及预后的关系.方法采用免疫组化法检测85例原发性乳腺癌VEGF—D的表达,以Podoplanin标记淋巴管内皮,计数淋巴管密度(LVD),采用RT—PCR法检测VEGF—DmRNA的表达.分析上述指标与临床病理指标及预后的关系.结果免疫组化检测显示,VEGF—D蛋白表达阴性5例(5.88%),"+"l7例(20%),"++"34例(40%),"+++"22例(25.88%),"++++"7例(8.24%),其表达与淋巴结转移,临床分期相关(P《0.01),且导致较差的生存率(P《0.05).LVD于不同表达程度的VEGF—D组间有显着差异(P《0.01),且随着VEGF—D表达的增加,LVD有上升的趋势.RT—PCR检测显示,VEGF—DmRNA在乳腺癌中的表达显着高于对照组(P《0.O1),且其表达与淋巴结转移,临床分期和LVD相关(P《0.05).结论VEGF—D在乳腺癌中具有一定的诱导淋巴管生成的作用,并与肿瘤的淋巴侵袭转移及预后相关.关键词:乳腺癌;血管内皮生长因子D;淋巴管生成:R737.9文献标志码:ARoleofVEGF-DinlymphangiogenesisofbreastcancerandrelationshipwithprognosisQlXiao—liang,GUYan,ZHANGRui,GUOShan—yu',XIAYong—feng,HELiu',TANGTing—ting,BAOYong—yang(J.DepartmentofGeneralSurgery,2.LaboratoryofOrthopedics,3.DepartmentofPathology,ShanghaiNinthPeopleHospital,SchoolofMedicine,Shanghai激aotongUniversity,Shanghai200011,China)Abstract:ObjectiveToevaluatetheroleofvascularendothelialgrowthfactor—D(VEGF—D)inlymphangiogenesisofbreastcancer,andinvestigateitsrelationshipwithsomeclinicopathologicalparametersandprognosis.MethodsVEGF—Dexpressionwasdetectedin85caseswithprimarybreastcarcinomabyimmunohistochemistry,andVEGF—DmRNAwasdetectedbyRT—PCR.Podoplaninmonoclonalantibodywasusedtomarklymphaticendothelialcellandlymphaticvesseldensity(LVD)wascounted.Therelationshipamongtheabovedparameters,clinicopathologicalparametersandprognosiswasanalysed.ResultsItwasrevealedbyimmunohistochemistrythatVEGF—Dexpressionwasrankedby5levels:negative,n=5(5.88%);"+",n=17(20%);"++",n=34(40%);"+++",n=22(25.88%),and"+卅",n=7(8.24%).VEGF—DexpressionwasassociatedwithtumorlymphnodemetastasisandTNMclinicalstage(P《0.01),andledtoaworseoutcome(P《0.05).LVDdifferedsignificantlybetweendifferentexpressionlevelsofVEGF—D(P《0.01).Moreover,LVDincreasedwiththeVEGF—Dexpressionleve1.ItwasindicatedbyRT—PCRthatVEGF—DmRNAexpressionwassignificantlyhigherthanthatofcontrol(P《0.O1),andwassignificantlyassociatedwithtumorlymphnodemetastasis,TNMclinicalstageandLVD(P《0.05).ConclusionVEGF—Dmayinducelympha"giogenesis,andmaybeassociatedwithlymphnodeinvasionandprognosisinbreastcancer.Keywords:breastcancer;vascularendothelialgrowthfactor—D;lymphangiogenesis目前,乳腺癌的发病率正逐年上升,已成为女性最常见的恶性肿瘤之一.淋巴道侵袭和淋巴结转移是乳腺癌细胞远处转移的主要途径之一,也是导致预后不良的重要因素,因此,乳腺癌的抗淋巴管生成的治疗可能成为一种有效的肿瘤治疗方法.血管内皮生长因子(vascularendothelialgrowthfactor,VEGF).D属于VEGF家族,在人类基因定位于染色体Xp22.31,其作用受体为淋巴管内皮表面的VEGF受体(VEGFreceptor,VEGFR)一2和VEGFR-3,通过酪氨酸激酶信号系统发挥作用,促进淋巴管上皮的增生和迁移….Stacker等的动物模型研究表明,VEGF—D的过表达可促进瘤内淋巴管的形成和淋巴结转移.但在人乳腺癌中,VEGF-D在...