乳腺癌组织中血管内皮生长因子的表达及其与临床病理指标的关系
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摘要
目的:乳腺癌是女性最常见的恶性肿瘤之一,其转移、复发是影响乳腺癌生存质量与生存时间的重要原因。本文通过对50例乳腺癌组织病理蜡块中血管内皮生长因子(VEGF)的测定,分析①与50例乳腺癌患者年龄,肿瘤大小,淋巴结转移情况,临床病理分期的差异性及相关性;②VEGF的表达与50例乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)表达的相关性;③乳腺癌组织中各分子分型中VEGF的差异性及相关性。
方法:收集我院普外科2007年住院手术的女性原发乳腺癌患者蜡块标本50例为研究对象,这些标本都有完整的临床病理资料,采用MaxVision快捷免疫组化染色检测50例乳腺癌蜡块组织VEGF的表达情况,并通过光学显微镜分析免疫组化的结果。然后用卡方检验(χ2)及秩相关(Spearman)分析VEGF在各临床及病理指标的差异性和相关性。
结果:50例乳腺癌患者中VEGF表达阳性者有32例,阳性表达率为64%;不同年龄组间无明显差异(P=0.774),VEGF表达与肿瘤大小呈正相关(P<0.001;R=0.635),与淋巴结转移有无呈正相关(P<0.001;R=0.721),与乳腺癌TNM分期呈正相关(P=0.007;R=0.380);VEGF与ER、PR呈负相关(R=-0.343,0.330),与Her-2表达呈正相关(R=0.290);在乳腺癌不同分子分型间表达有差异性,与其预后呈正相关(R=0.517)。
结论:VEGF是判断乳腺癌预后的重要指标之一;可以用来指导辅助化疗及内分泌治疗;可以成为TNBC的治疗靶点。
Objective: Breast cancer is one of the most common malignancy of women。The metastasis and recurrence are the key points effecting the quality of life and survival time of breast cancer patients. Based on the determination of vascular endothelial growth factor (VEGF) in 50 cases of breast cancer pathology paraffin blocks, we investigate:①The variability and correlations of VEGF expression in different ages, tumor size, lymph node metastasis, clinical staging of the fifty breast cancer patients.②The correlations of VEGF and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2(Her-2)expression in the fifty breast cancer patients.③The variability and correlations of VEGF expression in different molecular classification.
Methods: Collect 50 cases of paraffin blocks of primary breast cancer specimens who had opretions in the general surgery in our hospital in 2007 for study. These samples all have complete clinical data.Use MaxVision quickly immunohistochemistry to detect the expression in these breast cancer issue, and analysis the immuohistochemistry results by optical microscopy.Then use the chi-square test (χ2) and rank correlation (Spearman) to analysis the relevance of VEGF and various clinical pathological index.
Results: In the 50 breast cancers, the positive rate of VEGF is 64%(32/50).The expression of VEGF is significantly positive correlated to the size and the pathogistological type of tumors(r=0.635,0.380,respectively). When lympho node matastasis occurs, the more lymphonodes metastasis, the more VEGF expressed. But the expression of VEGF do not correlated with the ege of the breast cancer patients. ER and PR expression is negative correlated with VEGF expression(r= R=-0.343,0.330,respectively), while the HER-2 expression if positive correlated with VEGF expression(r=0.290). In different types of breast cancers, VEGF expression also differenated, is correlated with the prognosis of different types(P=0.03,r=0.517).
Conclusions: VEGF expression is one of the key factors effecting the prognosis of breast cancers, considering its correlations with ER,PR,HER-2, its relative therapies could be used or added into the Conventional treatment of breast cancers, especially used to treat the triple negative breast cancer.
方法:收集我院普外科2007年住院手术的女性原发乳腺癌患者蜡块标本50例为研究对象,这些标本都有完整的临床病理资料,采用MaxVision快捷免疫组化染色检测50例乳腺癌蜡块组织VEGF的表达情况,并通过光学显微镜分析免疫组化的结果。然后用卡方检验(χ2)及秩相关(Spearman)分析VEGF在各临床及病理指标的差异性和相关性。
结果:50例乳腺癌患者中VEGF表达阳性者有32例,阳性表达率为64%;不同年龄组间无明显差异(P=0.774),VEGF表达与肿瘤大小呈正相关(P<0.001;R=0.635),与淋巴结转移有无呈正相关(P<0.001;R=0.721),与乳腺癌TNM分期呈正相关(P=0.007;R=0.380);VEGF与ER、PR呈负相关(R=-0.343,0.330),与Her-2表达呈正相关(R=0.290);在乳腺癌不同分子分型间表达有差异性,与其预后呈正相关(R=0.517)。
结论:VEGF是判断乳腺癌预后的重要指标之一;可以用来指导辅助化疗及内分泌治疗;可以成为TNBC的治疗靶点。
Objective: Breast cancer is one of the most common malignancy of women。The metastasis and recurrence are the key points effecting the quality of life and survival time of breast cancer patients. Based on the determination of vascular endothelial growth factor (VEGF) in 50 cases of breast cancer pathology paraffin blocks, we investigate:①The variability and correlations of VEGF expression in different ages, tumor size, lymph node metastasis, clinical staging of the fifty breast cancer patients.②The correlations of VEGF and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2(Her-2)expression in the fifty breast cancer patients.③The variability and correlations of VEGF expression in different molecular classification.
Methods: Collect 50 cases of paraffin blocks of primary breast cancer specimens who had opretions in the general surgery in our hospital in 2007 for study. These samples all have complete clinical data.Use MaxVision quickly immunohistochemistry to detect the expression in these breast cancer issue, and analysis the immuohistochemistry results by optical microscopy.Then use the chi-square test (χ2) and rank correlation (Spearman) to analysis the relevance of VEGF and various clinical pathological index.
Results: In the 50 breast cancers, the positive rate of VEGF is 64%(32/50).The expression of VEGF is significantly positive correlated to the size and the pathogistological type of tumors(r=0.635,0.380,respectively). When lympho node matastasis occurs, the more lymphonodes metastasis, the more VEGF expressed. But the expression of VEGF do not correlated with the ege of the breast cancer patients. ER and PR expression is negative correlated with VEGF expression(r= R=-0.343,0.330,respectively), while the HER-2 expression if positive correlated with VEGF expression(r=0.290). In different types of breast cancers, VEGF expression also differenated, is correlated with the prognosis of different types(P=0.03,r=0.517).
Conclusions: VEGF expression is one of the key factors effecting the prognosis of breast cancers, considering its correlations with ER,PR,HER-2, its relative therapies could be used or added into the Conventional treatment of breast cancers, especially used to treat the triple negative breast cancer.
引文
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[1] Schedin P, Elias A.Multistep tumorigenesis and the microenvi-ronment[J].Breast Cancer Res.2004,6(2):93–101.
[2] Guinebretiere JM, Le Monique G, GavoilleA,et al.Angiogenesis and risk of breast cancerin women with fibrocystic disease[J]. J Natl CancerInst.1994,86(8):635-636.
[3] Guidi AJ, Fischer L, Harris JR,et al.Microvessel density and distribution in ductal carcinoma in situ of the breast[J]. J Natl CancerInst.1994,86(8):614-619.
[4] Weidner N, Semple JP, Welch WR,et al.Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma[J].N Engl J Med.1991,324(1):1-8.
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[6] Pidgeon G, Harmey J, Foley D,et al.Vascular endothelial growth factor (VEGF) upregulates Bcl-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells[J].Br J Cancer.2001,85(2):273–278.
[7] Weis S, Cheresh D.Pathophysiological consequences of VEGF induced vascular permeability[J].Nature.2005,437(7058):497–504.
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[2]张思维,陈万青.中国部分市县1998-2002年恶性肿瘤的发布与死亡.中国肿瘤.2006,15(7):430-448.
[3] Guinebretiere JM, Le Monique G, GavoilleA,et al.Angiogenesis and risk of breast cancerin women with fibrocystic disease[J]. J Natl CancerInst.1994,86(8):635-636.
[4] Guidi AJ, Fischer L, Harris JR,et al.Microvessel density and distribution in ductal carcinoma in situ of the breast[J]. J Natl CancerInst.1994,86(8):614-619.
[5] Weidner N, Semple JP, Welch WR,et al.Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma[J].N Engl J Med.1991,324(1):1-8.
[6] Weidner N, Folkman J, Pozza F,et al.Tumor angiogenesis: A new significant and independent prognostic indicator in early-stagebreast carcinoma[J]. J Natl Cancer Inst.1992,84(24):1875-1887.
[7] Pidgeon G, Harmey J, Foley D,et al.Vascular endothelial growth factor (VEGF) upregulates Bcl-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells[J].Br J Cancer.2001,85(2):273–278.
[8] Weis S, Cheresh D.Pathophysiological consequences of VEGF induced vascular permeability[J].Nature.2005,437(7058):497–504.
[9] Takanami I,Tanaka F, Hashizume T,et al.Vascular endothelial growth factor and its receptor with angiogenesis and surgovainpulmonary adeno carcinoma[J].Anti Cancer Res. 1997, 17 (4A):2811-2814.
[10] Arthur M, Mercurio·Elizabeth A, Lipscomb·Robin E, et al.Non-angiogenic functions of VEGF in breast cancer. J mammary gland neoplasia,2005,10:283-290.
[11] Harold F. Dvorak.Vascular permeablitity factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J clin oncol, 2002,20:4368-4380.
[12] Zhican Qu, Sabrina Van Ginkel, Snshu M. Roy, et al.Vascular endothelial growth factor reduces tamoxifen efficacy and promotes metastatic colonization and desmoplasia in breast tumors.Cancer Res 2008.2008,68(15):6232-6240.
[13] Arthur M, Mercurio, Elizabeth A, et al.Non-angiogenic funtions of VEGF in breast cancer.J mammary gland boil neoplasia.2005,10:283-290.
[14] Schedin P, Elias A.Multistep tumorigenesis and the microenvi-ronment[J].Breast Cancer Res.2004,6(2):93–101.
[15] Emly C.Maambo,MD,Olga B.loffe,MD.Molecular classification and prognostication of breast cancer.Pathology case reviews.2009,14:129-134.
[16]韩明利,吴诚义.乳腺癌分子分型的研究进展.中国普通外科杂志.2009,18(11):1180-1183.
[17]赵晶,付丽.乳腺癌的分子分型.中华乳腺病杂志(电子版).2009,3(2):195-203.
[18] Miller K,Sledge GW:Dimming the blood tide: Angiogenesis, antiangiogenic therapy and breast cancer, in Nabholtz JM (ed): Breast Cancer Management Application of Clinical and Translational Evidence to Patient Care (ed 2nd).Philadelphia, PA, Lippincott Williams & Wilkins,2003, pp 287-308.
[19]林燕苹、陆劲松、邵志敏等.乳腺癌辅助内分泌治疗进展[J].复旦学报(医学版).2009,36(2):235-238.
[20]陈进宏.乳腺癌的辅助内分泌治疗[J].现代医院. 2009,9(4):46-47.
[21]任国胜,甘露.乳腺癌辅助内分泌治疗[J].中国普外基础与临床杂志.2007,14(3):248-251.
[22] Lisa Rydén, Karin Jirstr?m, Pa¨r-Ola Bendahl et al.Tumor-specific expression of vascular endothelial growth factor receptor 2 but not vascular endothelial growth factor or human epidermal growth factor eeceptor 2 is associated with impaired response to adjuvant tamoxifen in premenopausal breast cancer[J]. Journal of clinical Oncology.2005,23 (21) :4695-4704.
[23]敬静,赵扬冰,李宏江等.乳腺癌患者治疗前后血清VEGF水平变化及其临床意义[J].四川大学学报(医学版),2006 ;37(6) :889-892.
[24]Chris E. Holmes, Joe C. Huang, Thomas R. Pace, et al.Tamoxifen and Aromatase inhibitors differentially affect vascular endothelial growth factor and endostatin levels in women with breast cancer[J]. Clin Cancer Res. 2008,14(10):3070-3076.
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