HIF - 1α 的表达与乳腺癌临床病理特征及预后的研究

目的：分析缺氧诱导因子1仪（HIF—1a）、缺氧相关蛋白血管上皮生长因子A（VEGF—a）和葡萄糖转运蛋白-1（GLUT-1）在非特殊浸润性乳腺癌中的表达情况。运用流行病学与统计学方法分析HIF-10t与乳腺癌临床病理学特征及预后的关系。方法：采用免疫组化法检测HIF～1a、VEGF—a及GLUT-1在163例非特殊浸滑l生乳腺癌中的表达晴况；分析HIF—1a．VEGF—a及GLUT—1的表达与乳腺癌临床病理特征的关系；对HIF—l仪表达不同的乳腺癌患者进行生存分析，检验其预后意义；分析HIF-1a与缺氧相关蛋白VEGF—a和GLUT-1的表达水平的相关性；多因素分析HIF-10t的表达与临床病理资料是否为独立危险因素。结果：HIF-1a在163例非特殊浸润性乳腺癌的表达情况：阴性表达94例（57．7％），阳性表达69例（42．3％）。HIF-1a的表达情况与乳腺癌高TNM分期、分化差的分子分型、组织病理分型、复发情况密切相关。对HIF-1仪表达不同的病例进行生存分析，显示HIF-10t阴性表达的病例预后好于阳性表达病例（P〈0．05）。缺氧相关蛋白VEGF—a和GLUT-1的表达情况：VEGF—a表达阳性95例（58．3％），阴性68例（41．7％）；GLUT-1表达阳性126例（77．3％），阴性37例（22．7％）。HIF-1ot与VEGF—a表达呈显著正相关，相关系数为0．538和0．668，与GlUT-1表达情况为中等程度负相关，相关系数为-0．31和-0．40。Cox多因素分析显示，HIF-1饯阳性表达、高TNM分期、非腺管型分子分型是影响乳腺癌预后的独立危险因素，相对危险度分别为1．41、4．56、3．47。结论：HIF—1a广泛表达于乳腺癌组织中，其表达与乳腺癌的TNM分期、分子分型和病理类型密切相关。生存分析显示：HIF-1a高表达是影响乳腺癌预后的独立危险因素。HIF-1d与缺氧相关蛋白VEGF—a的表达呈正相关，证明其参与了缺氧调控的乳腺癌微环境改变。

The relationship of expression of HIF - 1a and clinicopathological characteristics and prognosis of breast cancer

Objective： To investigate the expression of HIF - 1 a, hypoxia - related protein VEGF - a and GLUT - 1 in non- specific invasive breast cancer, and analyze the relationship between the expression of HIF - l oL, clinical and pathological characteristics and the prognosis of the breast cancer. Methods： Immunohistochemical analysis was used to detect the expression of HIF - lct,VEGF - a and GLUT - 1 in 163 non - specific invasive breast cancer speci- mens. Kaplan - meier method was used to analyze the prognostic value. Kendall and Spearman~ rank coefficient were calculated to estimate the dependability of HIF - 1a, VEGF - a and GLUT - 1 expression. Multiple factor Cox regres- sion was used to analyze if expression of HIF -lct and certain clinicpathological characteristics were independent risk fac- tors. Results： The expression of HIF - 1 ct in 163 breast cancer specimens ：57.7% were negative （94 of 163 ） ,42.3 % were positive（69 of 163 ）. The expression of HIF - l a was closely related to the TNM staging, molecular subtypes, pathological types and the recurrence. HIF - la negative patients have better prognosis（ P 〈 0.05 ）. Expression of hy- poxia - related proteins VEGF - a and GLUT - 1 in breast cancer specimens ：58.3% were VEGF - a positive（95 of163 ） ,and 41.7% were negative（68 of 163 ） ;while 77.3% were GLUT - 1 positive（ 126 of 163） ,and 22.7% nega- tive（37 of 163 ）. Correlation analysis revealed there was distinguished positive correlation between the expression of HIFla and VEGF - a（ related coefficients were 0.538 and 0.668 ） ,while the expression of HIF - la and GLUT - 1 was negatively correlated（ related coefficients were- 0.31 and- 0.40 ）. Multiple factor Cox regression illustrated the positive expression of HIF - 1 a,late TNM stage and non - glandular molecular subtypes of breast cancer were inde- pendent risk factors. The RR value was 1.41,4.56 and 3.47. Conclusion： HIF - la is found widely expressed in breast cancer,which affects the biological characteristics of breast cancer. The high expression of HIF - la is an inde- pendent risk factor of breast cancer prognosis. There are positive correlations between HIF - 1 a and hypoxia - related protein VEGF - a. They participate in the regulation of breast cancer microenvironment which is induced by hypoxia.