联合检测多基因在乳腺癌组织中的表达及其临床意义  

The expression and clinical significance of multi-genes in breast cancer

作　　者：黄宝俊[1] 徐惠绵[1] 李凯[1] 王怀宇[2] 张昊[1] 田大彤 

机构地区：[1]中国医科大学附属第一医院肿瘤外科,辽宁沈阳110001 [2]沈阳市皇姑区中心医院,辽宁沈阳110036 [3]辽宁省妇婴医院妇产科,辽宁沈阳110005

出　　处：《中国普通外科杂志》2005年第4期247-252,共6页China Journal of General Surgery

摘　　要：目的探讨ER,PR,p53(突变型,下同),HER2,MDR1基因在乳腺癌组织中表达,及其与临床病理因素的相关性和预后的关系。方法采用免疫组化SP法检测上述基因在215例乳腺癌中的表达情况,分析其与临床病理因素的相关性;随访全组病例的无病生存率和总生存率,进行生存分析。结果ER,PR,p53,HER2,MDR1在全组病例中表达的阳性率分别为40.9%,27.0%,40.5%,37.2%,37.7%;PR和p53表达增高者多伴有腋淋巴结转移(P=0.001,0.037);HER2表达增高者TNM分期相对较晚(多为III期)、腋淋巴结转移程度相对较重(常在5个以上)(P=0.012,0.037);上述基因表达与其他临床病理因素间无明显关系(P>0.05)。MDR1与p53,HER2间具有显著的正相关关系(P=0.020,rs=0.159;P=0.014,rs=0.168);而ER,PR与HER2间无明显相关性(P>0.05)。单因素生存分析发现TNM分期、腋淋巴结有无转移及程度、p53和HER2表达与乳腺癌患者的无病和总生存率相关;而MDR1表达亦与总生存率相关。多因素生存分析发现腋淋巴结转移情况、MDR1和HER2表达是影响预后的独立危险因素。结论p53,HER2,MDR1对预后的影响可能是通过诱导乳腺癌细胞耐药及对内分泌治疗反应下降所致。联合检测上述基因在乳腺癌中的表达,有助于判断乳腺癌的恶性程度、转移表型和预后;p53,HER2。Objective To study the expressions of ER, PR, mutant p53, HER2, and MDR1 genes in breast cancer, and their correlation with clinicopathologic factors and prognosis.Methods Expressions of ER, PR, mutant p53, HER2, and MDR1 gene proteins were examined by immunohistochemistry (IHC) in breast cancer lesions from 215 patients, and their correlation with clinicopathologic features were analyzed.All of the patients were followed up for analysis of disease free survival(DFS) and overall survival(OS) rate, and survival analysis. Results Of the 215 breast carcinoma samples, the positive rates for ER、PR、mutant p53,HER2,MDR1 gene proteins expression were 40.9%,29.0%,40.5%,37.2% and 37.7%, ~respectively . Over-expression of PR and mutant p53 was positively correlated with axillary lymph node (P=0.001, 0.037, respectively), and over-expression of HER2 was positively correlated with TNM staging and extent of axillary lymph node metastasis(P=0.012,0.037, respectively). The genes expressions were not significantly correlated with other clinicopathologic factors(P>0.05). Expression of MDR1 had a positive ~correlation with mutant p53 accumulation and HER2 expression(P<0.05 ). ER and PR expressions were not significantly correlated with HER2 expression(P>0.05 ).In univariate analyses,TNM staging, axillary lymph node metastasis, mutant p53 accumulation, and HER2 over-expression were negatively correlated with DFS and OS, and MDR1 over-expression significantly reduced OS but not DFS. In multivariate analysis, axillary lymph node metastasis, over-expression of MDR1 and HER2 were independent risk factors for prognosis. Conclusions ~Induction of multidrug resistance and poor response to chemotherapy and endocrinotherapy may be the chief reasons for poor prognosis of breast cancer with mutant p53 accumulation, and HER2 and MDR1 over-expression. ~Determination of the above genes′expression in breast cancer tissue can be of use in deciding the degree of ~malignancy , metastasis phenotype and prognosis of

关 键 词：乳腺肿瘤/病理学 癌基因表达 淋巴转移 

分 类 号：R737.9[医药卫生—肿瘤] R730.23[医药卫生—临床医学]