乳腺癌中KiSS-1与核因子-κBp50和基质金属蛋白酶9的表达之相互关系及其临床病理意义

目的 探讨KiSS-1、核因子(NF)-κBp50和基质金属蛋白酶9(MMP-9)在乳腺癌组织中的表达和相互关系及其临床病理意义.方法 应用免疫组织化学EliVision法检测152例标本(乳腺癌92例,乳腺增生30例,癌旁乳腺30例)和伴有癌转移的腋窝淋巴结54枚中KiSS-1、NF-κBp50及MMP-9蛋白表达情况.应用原位杂交方法检测50例乳腺癌组织、20例癌旁乳腺组织中KiSS-1mRNA的表达.应用CMIAS真彩图像分析仪对免疫组织化学和原位杂交结果进行积分吸光度(IA)值测定,并计算其平均IA值.结果 (1)与癌旁乳腺组织表达比较,KiSS-1基因在乳腺癌组织学分级Ⅰ～Ⅱ级中(13.59±6.24)明显高于Ⅲ级(9.53±4.57)、TNM分期高(Ⅰ～Ⅱ期12.35±6.15,Ⅲ～Ⅳ期7.53±4.93)、在淋巴结转移率高的乳腺癌中的表达减弱(9.61±5.25,无转移组为13.06±5.89)甚至缺失;其在淋巴结转移灶(3.47±1.59)中的表达(IA值)明显低于其相应的原发灶(10.02±3.80).乳腺癌组织中KiSS-1 mRNA表达(10.84±4.90)与KiSS-1蛋白表达(11.67±6.22)有较好的一致性.(2)NF-κBp50、MMP-9在乳腺癌组织中表达上调,其上调程度随着乳腺癌分化程度的降低、TNM分期的增加、淋巴结转移及瘤块增大而逐渐增高.结论 KiSS-1蛋白在乳腺癌分化程度低、淋巴结转移组中的表达下降,并分别与NF-κBp50、MMP-9蛋白表达呈负相关;NF-κBp50与MMP-9蛋白在乳腺癌中表达呈正相关,KiSS-1蛋白可能参与了乳腺癌的转移扩散.

Relationship and clinical significance of KiSS-1,nuclear factor kappa B(NF-κB)p50,and matrix metalloproteinase 9 expression in breast cancer

Objective To study the expression of KiSS-1,nuclear factor kappa B(NF-κB)p50 and matrix metalloproteinase 9(MMP-9)in breast cancer tissue and the relationship with clinicpathological factors.Methods Immunohistochemical staining for KiSS-1.NF-κBp50.and MMP-9 protein was performed in 152 cases of human breast tissue 92 cases of BC,30 cases of epithelial hyperplasia,and 30 cases of peritumoral breast tissue(PMT)] and 54 cases of axillary lymph node metastases.In-situ hybridization for KiSS-1 mRNA was done in 50 cases of breast cancer.and 20 cases of PMT.Results (1)The expression of KiSS-1 gene was significantly higher in well-differentiated breast cancer than in PMT.and this expression progressively decreased with decreasing degree of tumor differentiation,increasing pathological grade.TNM stage and the presence of lymph node metastases.The expression of KiSS-1 gene in lymph node metastasis was markedly lower than the corresponding primary tumor.There was correlation between the expression of KiSS-1 mRNA and KiSS-1 protein in breast cancer group.(2)The expression of NF-κBp50 and MMP-9 increased progressively with decreasing degree of tumor differentiation,increasing TNM stage,large tumor size(＞2 cm)and the presence of lymph node metastases.Conclusions The expression of KiSS-1 protein showed negative correlation with that of NF-κBp50 and MMP-9 respectively.MMP-9 protein expression was positively correlated with NF-κp50 protein expression.These suggest that the genes of KiSS-1.NF-κBp50 and MMP-9 could be involved in the progression and metastasis of breast Cancer.