乳腺癌3p染色体微卫星杂合性缺失与血管生成

目的探讨乳腺癌染色体3p区域微卫星杂合性缺失(LOH)与血管内皮生长因子(VEGF)蛋白表达及临床病理特征之间的关系。方法选取乳腺浸润性导管癌病例石蜡组织切块40例。运用激光显微切割技术留取组织中导管癌及正常乳腺细胞,应用毛细管电泳测序技术进行4个微卫星位点的LOH检测。应用免疫组织化学技术SP法检测CD34、VEGF和Her2的表达,分析LOH与乳腺癌临床病理参数的关系。结果 40例乳腺癌患者中D3S1038的LOH发生率为20%(8/40),D3S1295的LOH发生率为37.5%(15/40),D3S1581的LOH发生率为17.5%(7/40),D3S3118的LOH发生率为5%(2/40)。LOH与VEGF的表达呈正相关(r=0.658 0,P<0.01),LOH和MVD也呈正相关(r=0.804 9,P<0.01)。LOH发生率与Her2表达(r=0.539 4)、组织学分级(r=0.497 2)、淋巴结转移(r=0.506 4)、TNM分期(r=0.596 0)均有相关性(均P<0.01)。结论乳腺癌染色体3p微卫星位点LOH与血管生成具有相关性,抑癌基因失活并通过对血管生成的影响可能为肿瘤生长与转移提供了条件;同时检测染色体3p微卫星位点LOH与血管生成情况,可能有助于更全面地了解乳腺癌的生物学特性。

Loss of heterozygosity at chromosome 3p microsatellite loci and angiogenesis in breast cancer

ObjectiveTo explore the association of loss of heterozygosity (LOH) at chromosome 3p and vascular endothelial growth factor(VEGF) expression with clinicopathological features of breast cancer. MethodsA total of 40 specimens of breast invasive ductal carcinoma were analyzed in the present study. The ductal carcinoma cells and normal breast cells were microdissected from the paraffin sections. Capillary electrophoresis method was used to detect LOH of four microsatellite loci located in the 3p site. Immunohistochemical staining was used to investigate the expression of CD34, VEGF and Her2 proteins in the 40 specimens. The association of LOH with the clinicopathological characteristics of breast carcinoma was evaluated. ResultsWe found that in the 40 specimens LOH of D3S1038 was 20%(8/40), LOH of D3S1295 was 37.5%(15/40), LOH of D3S1581 was 17.5%(7/40), and LOH of D3S3118 was 5%(2/40). LOH was positively correlated with expression of VEGF (r=0.658 0, P<0.01) and MVD (r=0.804 9, P<0.01). We also found that LOH was significantly related to Her2 (r=0.539 4), differentiation(r=0.497 2), lymph node metastasis(r=0.506 4), and TNM stage(r=0.596 0, all P<0.01). ConclusionLOH at chromosome 3p microsatellite loci is correlated with angiogenesis. Inactivation of tumor suppressor may influence angiogenesis and subsequently promote tumor growth and metastasis. Detection of LOH at chromosome 3p microsatellite loci together with angiogenesis can help to fully understand the biological characteristics of breast cancer.