血管生成素样蛋白3、4在浸润性乳腺癌中的表达及临床意义

Expressions of Angptl 3 and Angptl 4 in invasive breast cancer and clinical significance

目的检测血管生成素样蛋白（angiopoietin-like protein,Angptl）3和Angptl 4在浸润性乳腺癌组织中的表达及其临床意义,为乳腺癌的治疗及预后提供有价值的生物学指标。方法用随机数字表法收集苏北人民医院2007—2009年手术切除浸润性乳腺癌标本70例,乳腺纤维腺瘤标本30例,采用免疫组织化学SP法,检测肿瘤标本中Angptl 3和Angptl 4的表达。采用χ^2检验分析两种蛋白在乳腺癌和乳腺纤维腺瘤中是否具有表达差异性,χ^2检验和Fisher确切概率法分析两种蛋白与乳腺癌临床病理特征之间的关系,Spearman相关分析法分析Angptl 3和Angptl 4两种蛋白在浸润性乳腺癌中表达的相关性,并采用Kaplan-Meier法及Cox比例风险模型进行浸润性乳腺癌患者的生存分析。结果 Angptl 3在浸润性乳腺癌和乳腺纤维腺瘤中的阳性表达率分别为75.7%（53/70）和46.7%（14/30）（χ^2=8.014,P=0.005）,Angptl 4在浸润性乳腺癌和乳腺纤维腺瘤中的阳性表达率分别是68.6%（48/70）和36.7%（11/30）（χ^2=8.837,P=0.003）,差异均有统计学意义。Angptl 3的表达在不同肿瘤直径、腋窝淋巴结转移、TNM分期、ER表达的患者中差异有统计学意义（χ^2=6.000、5.598、9.714、8.753,P〈0.050）。在70例浸润性乳腺癌中,Angptl 4的表达在不同肿瘤直径、腋窝淋巴结转移、TNM分期的患者中差异有统计学意义（χ^2=8.762、6.526、5.701,P〈0.050）。Angptl 3和Angptl 4表达呈正相关（P=0.005,r=0.334）。Kaplan-Meier分析结果表明,Angptl 3和Angptl 4阴性表达的患者总生存期均优于阳性表达的患者（χ-2=9.376、7.628,P=0.002、0.006）。Cox多因素生存分析结果表明,年龄、组织学分级、肿瘤直径、ER、PR是影响预后的独立危险因素（OR=6.379、0.033、66.678、0.014、0.094,P均〈0.050,95%CI：1.380-29.482、0.002-0.598、5.433-818.294、0.001-0.183、0.012-0.724）,Angptl 3和Angptl 4蛋白表达不是影响浸润性乳腺癌患者预后的独立因素（OR=1.262、1.841,P=0.937、0.695,95%CI：0.000-2.281、0.087-39.051）。结论 Angptl 3和Angptl 4在浸润性乳腺癌中高表达,且两者呈正相关。两者阳性表达的患者生存期缩短,但两者均不是影响浸润性乳腺癌患者预后的独立因素。

Objective To detect the expressions of angiopoietin-like proteins（Angptl）3 and Angptl 4in invasive breast cancer and the clinical significance,and explore the potentials as biomarkers for the treatment and prognosis of breast cancer. Methods The tumor samples surgically resected from 70 cases of invasive breast cancer and 30 cases of breast fibroadenoma in Subei People＇s Hospital from 2007 to 2009 were collected to determine the expressions of Angptl 3 and Angptl 4 with immunohistochemical SP method. χ~2test was used to analyze the expression difference of these two proteins between invasive breast cancer and breast fibroadenoma.χ~2test and Fisher＇s exact probability method were used to analyze the relationship between the protein expression and clinicopathological characteristics of invasive breast cancer. Spearman correlation analysis was used to detect the correlation between Angptl 3 and Angptl 4 in invasive breast cancer. KaplanMeier method and Cox model were used for survival analysis. Results The positive rate of Angptl 3 was75. 7%（53 / 70）in invasive breast cancer and 46. 7%（14 / 30）in breast fibroadenoma（χ~2= 8. 014,P =0. 005）;the positive rate of Angptl 4 was 68. 6%（48 / 70）in invasive breast cancer and 36. 7%（11 / 30）in breast fibroadenoma（χ~2= 8. 837,P = 0. 003）,both indicating a significant difference. In 70 cases of invasive breast cancer,Angptl 3 expression showed a significant difference in patients with different tumor size,axillary lymph node metastasis,TNM stage and ER status（χ~2= 6. 000,5. 598,9. 714,8. 753,P 0. 050）;Angptl 4expression showed a significant difference in patients with different tumor size,axillary lymph node metastasis and TNM stage（χ~2= 8. 762,6. 526,5. 701,P0. 050）;Angptl 3 was positively correlated with Angptl 4（P =0. 005,r = 0. 334）. Kaplan-Meier analysis showed that the survival in patient with Angptl 3 / Angptl 4 positive was superior to that in patient with Angptl 3 / Angptl 4 negative（χ~2= 9. 376,7. 628;P = 0. 002,0. 006）. Cox multivariate survival analysis showed that age, histological grade, tumor size, ER and PR status were independent risk factors in prognosis of invasive breast patients（OR = 6. 379,0. 033,66. 678,0. 014,0. 094;all P 0. 050;95% CI：1. 380- 29. 482,0. 002- 0. 598,5. 433- 818. 294,0. 001- 0. 183,0. 012- 0. 724）,while Angptl 3 and Angptl 4 expressions were not（OR = 1. 262,1. 841;P = 0. 937,0. 695;95% CI：0. 000- 2. 281,0. 087-39. 051）. Conclusions Angptl 3 and Angptl 4 are highly expressed in invasive breast cancer,with a positive correlation. The patients with Angptl 3 and Angptl 4 positive have a short survival,however the two are not the independent risk factors in the prognosis of invasive breast caner patients.