合并糖尿病的乳腺癌组织中缺氧诱导因子-1α的表达及其与微血管生成的关系

Expression of HIF-1α and correlation with angiogenesis in tissue of breast cancer complicated with diabetes

目的 探讨合并糖尿病的乳腺癌组织中缺氧诱导因子-1α（HIF-1α）的表达及其与血管内皮生长因子（VEGF）、微血管密度（MVD）的关系.方法 收集临床资料,回顾性分析合并2型糖尿病的乳腺癌患者（糖尿病组）和非糖尿病的乳腺癌患者（对照组）临床病理特征之间的差异.采用免疫组化SP法检测两组患者乳腺癌组织中HIF-1α及VEGF蛋白的表达,用CD31标记血管内皮细胞并计算MVD.结果 合并2型糖尿病的乳腺癌患者中肿瘤直径＞2 cm者占68.4％ （67/98）,淋巴结转移率为59.2％ （58/98）;对照组患者中肿瘤直径＞2 cm者占54.2％ （58/107）,淋巴结转移率为43.9％ （47/107）;两组比较差异均有统计学意义（均P＜0.05）.HIF-1α在两组乳腺癌组织中均有表达,在糖尿病组乳腺癌组织中阳性表达率为80.6％ （79/98）,对照组乳腺癌组织为64.5％ （69/107）,两组比较差异有统计学意义（P=0.010）.VEGF在两组乳腺癌组织中的阳性表达率分别为86.7％（85/98）及68.2％ （73/107）,两组比较差异有统计学意义（P =0.002）.MVD在两组乳腺癌组织中的计数分别为113.7±32.0及104.7 ±29.4,两组比较差异有统计学意义（P =0.003）.合并2型糖尿病的乳腺癌患者中HIF-1α阳性表达组中VEGF阳性表达率为91.1％ （72/79）,HIF-1 α阴性表达组为68.4％ （13/19）,HIF-1 α阳性表达组明显高于HIF-1α阴性表达组,两组比较差异有统计学意义（P=0.009）;两组的MVD计数分别为117.1 ±30.3和99.5 ±35.1,HIF-1 α阳性表达组明显高于HIF-1α阴性表达组,两组比较差异有统计学意义（P =0.030）.结论 糖尿病可能是导致乳腺癌患者临床分期较晚、预后较差的一个因素.合并糖尿病可能促使乳腺肿瘤组织中微血管生成作用增强,从而可能在乳腺癌的发生发展及转移机制中起到促进作用.

Objective To explore the expression of hypoxia-inducible factor 1 alpha （HIF-1 α）in tissue of breast cancer complicated with diabetes and examine the correlation with vascular endothelial growth factor（VEGF） and microvascular density （MVD）.Methods The clinical data were collected by reviewing the relevant medical records.The difference of clinicopathologic features between breast cancer patients with diabetes （diabetic group）and that of those without diabetes （control group） was analyzed retrospectively.Immunohistochemical Streptavidin-Perosidase （SP） method was used to detect the expressions of HIF-1 α and VEGF in breast cancer tissue of two groups.Vascular endothelial cells were tagged with CD31 to calculate MVD.Results The patients of tumor diameter 〉 2 cm were 68.4% （67/98） and lymphatic metastasis rate was 59.2% （58/98） in diabetes group.And those in control group were 54.2% （58/107） and lymphatic metastasis rate was 43.9% （47/107）.The inter-group difference was significant （P 〈0.05）.HIP-1α was expressed in both groups.The positive rate of HIF-1α was 80.6% （79/98） in diabetes group versus 64.5% （69/107） in control group （P =0.010）.The positive rate of VEGF was 86.7% （85/98） in diabetes group versus 68.2% （73/107） in control group （P =0.002）.MVD value was 113.7 ± 32.0 in diabetes group versus 104.7 ± 29.4 in control group （P =0.003）.The positive rate of VEGF in HIF-1 α positive patients of diabetes group was significantly higher than that in negative counterparts （91.1% vs 68.4%,P =0.009）.The values of MVD were 117.1 ± 30.3 and 99.5 ± 35.1 respectively in both groups.And the MVD value of HIF-1 α positive group was significantly higher than that of negative group （P =0.03）.Conclusion Diabetic complications may play critical roles in the development and metastasis of breast cancer through enhanced angiogenesis of tumor tissue.