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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2009, Vol. 03 ›› Issue (01) : 22 -31. doi: 10.3877/cma.j.issn.1674-0807.2009.01.006

临床研究

膜型基质金属蛋白酶-1 在乳腺癌中表达的预后价值
姚广裕1,2, 何萍3, 王曦1, 唐军1, 罗荣城2, 叶长生2, 王军业1, 戎铁华1, 杨名添1,†()   
  1. 1.510060 广州,中山大学附属肿瘤医院华南肿瘤学国家重点实验室
    2.510515广州,南方医科大学南方医院
    3.510120 广州,广州医学院第一附属医院病理科
  • 收稿日期:2008-07-23 出版日期:2009-02-01
  • 通信作者: 杨名添
  • 基金资助:
    国家“十五”科技攻关计划资助项目(2001BA703B04)

Prognostic significance of MT1-MMP expression in breast cancer

Guangyu YAO1, Ping HE1, Xi WANG1, Jun TANG1, Rong-cheng LUO1, Chang-sheng YE1, Jun-ye WANG1, Tie-hua RONG1, Ming-tian YANG†,1()   

  1. 1.State Key Laboratory of Oncology in Southern China; Cancer Hospital, Sun Yet-sen University, Guangzhou 510060, China
  • Received:2008-07-23 Published:2009-02-01
  • Corresponding author: Ming-tian YANG
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姚广裕, 何萍, 王曦, 唐军, 罗荣城, 叶长生, 王军业, 戎铁华, 杨名添. 膜型基质金属蛋白酶-1 在乳腺癌中表达的预后价值[J/OL]. 中华乳腺病杂志(电子版), 2009, 03(01): 22-31.

Guangyu YAO, Ping HE, Xi WANG, Jun TANG, Rong-cheng LUO, Chang-sheng YE, Jun-ye WANG, Tie-hua RONG, Ming-tian YANG. Prognostic significance of MT1-MMP expression in breast cancer[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2009, 03(01): 22-31.

目的

探讨膜型基质金属蛋白酶-1(MT1-MMP)蛋白在乳腺癌中表达的临床意义。

方法

采用免疫组织化学方法检测106 例乳腺癌患者手术标本中MT1-MMP 蛋白的表达;用统计学软件SPSS11. 0 作为统计分析的工具,MT1-MMP 表达与临床病理因子的关系用卡方检验和Pearson等级相关分析检验;预后分析采用Kaplan-Meier 检验Cox Regression。

结果

乳腺癌组织中MT1-MMP 蛋白表达阳性率为62.3%,表达强度在不同分期和不同淋巴结转移数目患者间差异有统计学意义且呈正相关(P ＜0.050),在不同大小肿瘤间及在ER、PR 和HER-2 不同表达的患者间差异无统计学意义。 MT1-MMP 阴性患者与弱至中度阳性或强阳性患者间的无病生存期比较, MT1-MMP( -)为65.0%,MT1-MMP( + ～)为27.1%,MT1-MMP()为27.8%,差异有统计学意义(P ＜0.050)。 不同MT1-MMP 免疫组织化学染色强度患者的7 年生存率也明显不同, MT1-MMP( -)为77.5%,MT1-MMP( + ～)为60.4%,MT1-MMP ()为50.0%,差异有统计学意义(P ＜0.050)。 根据不同分期和不同淋巴结转移状态分层分析发现,MT1-MMP 蛋白不同表达强度的患者预后差异有统计学意义(P ＜0.050);根据不同肿瘤大小的分层分析发现,不同MT1-MMP 表达强度的T2期和T4期患者预后差别有统计学意义(P ＜0.050),但T1和T3期患者预后没有差别。 多因素分析显示MT1-MMP 是有意义的预后因子,MT1-MMP 强阳性患者死亡风险增加2 倍,弱到中度阳性患者死亡风险增加1.3 倍。

结论

MT1-MMP 的表达与乳腺癌侵袭转移有关,MT1-MMP 是乳腺癌的预后因子。

关键词: 膜型基质金属蛋白酶-1, 乳腺肿瘤, 预后

Objective

To explore the clinical significance of MT1-MMP expression in breast cancer.

Methods

The MT1-MMP protein expression was detected in human breast cancer specimens from 106 patients by immunohistochemistry assay.Statistical analysis was performed using SPSS 11.0 statistical software. The correlation between MT1-MMP expression and other pathological variables in breast cancer was determined by the Chi-square test and Spearman rank correlation test. The Kaplan-Meier method and the Cox proportional hazard model were used for survival analysis.

Results

The expression of MT1-MMP protein was found in 62.3% of the breast samples.There was a positive correlation between advanced stage or lymph node involvement and MT1-MMP positivity(P＜0.050). No correlation was found between MT1-MMP immunoreactivity and tumor size, HER-2, estrogen or progesterone receptor status. The 7-year disease-free survival was remarkably different between patients with MT1-MMP negative tumors (65.0%) and with MT1-MMP weakly or moderately positive tumors(27.1%) or highly positive tumors (27.8%) (P＜0.050). The 7-year overall survival was significantly different in patients with different MT1-MMP expressions: MT1-MMP( -) was 77.5%; MT1-MMP ( + ～) was 60.4%; and MT1-MMP () was 50.0%, with statistically significant difference (P＜0.050). MT1-MMP positivity correlated significantly with shortened survival in patients with different lymphonode involvement and stage. The mortality rate was different in the patient groups with stage T2 and T4, but identical in the patient groups with T1 and T3. A multivariate analysis showed that MT1-MMP positivity in cancer cells maintained its association with a poor outcome. The relative risk increased by 1.3 times in the patients with weak or moderate positivity and by 2 times in the patients with highly positive tumors.

Conclusion

The expression of MT1-MMP is correlated with breast cancer aggression and metastasis.MT1-MMP expression in breast cancer is a prognostic factor .

Key words: Membrane type-1 matrix metalloproteinase; Breast neoplasms;Prognosis
图1 乳腺癌细胞MT1-MMP 阳性染色(S-P 染色 ×400)
表1 乳腺癌MT1-MMP 蛋白表达与临床病理因子的关系
临床病理因子 例数 MT1-MMP表达[例(%)] P值
- +～
肿瘤大小 0.635a
　T1 23 11(47.8%) 8(34.8%) 4(17.4%)
　T2 58 23(39.7%) 26(44.8%) 9(15.5%)
　T3 17 5(29.4%) 9(52.9%) 3(17.6%)
　T4 8 1(12.5%) 5(62.5%) 2(25.0%)
淋巴结转移 0.001a
　N0 37 23(62.2%) 11(29.7%) 3(8.1%)
　N1 46 15(32.6%) 22(47.8%) 9(19.6%)
　N2 23 2(8.7%) 15(65.2%) 6(26.1%)
分期 0.002a
　Ⅰ 9 6(66.7%) 2(22.2%) 1(11.1%)
　Ⅱ 72 32(44.4%) 30(41.7%) 10(13.9%)
　Ⅲ 25 2(8.0%) 16(64.0%) 7(28.0%)
ER 0.210
　- 60 19(31.7%) 28(46.7%) 13(21.7%)
　+ 46 21(45.7%) 20(43.5%) 5(10.9%)
PR 0.436
　- 64 21(32.8%) 31(48.4%) 12(18.8%)
　+ 42 19(45.2%) 17(40.5%) 6(14.3%)
HER-2 0.758
　- 57 20(35.1%) 26(45.6%) 11(19.3%)
　+ 49 20(40.8%) 22(44.9%) 7(14.3%)
图2 不同MT1-MMP 染色强度的患者无病生存曲线
图3 不同MT1-MMP 染色强度的患者生存曲线
表2 不同临床因子分层分析MT1-MMP 不同染色强度的预后
临床病理因子 例数 7年生存率 Log Rank检验(P值)
- +～
肿瘤大小
　T1 23 9/11(81.8%) 4/8(50.0%) 2/4(50.0%) 0.108
　T2 58 19/23(82.6%) 18/26(69.2%) 4/9(44.4%) 0.035
　T3 17 4/5(80.0%) 8/9(88.9%) 0/3(0.0%) 0.052
　T4 8 1/1(100.0%) 0/5(0.0%) 0/2(0.0%) 0.018
淋巴结转移
　N0 37 21/23(91.3%) 10/11(90.9%) 1/3(33.3%) 0.008
　N1 46 11/15(73.3%) 13/22(59.1%) 4/9(44.4%) 0.028
　N2 23 1/2(50.0%) 7/15(46.7%) 1/6(16.7%) 0.013
分期
　Ⅱ 72 26/32(81.3%) 20/30(66.7%) 5/10(50.0%) 0.047
　Ⅲ 25 1/2(50.0%) 8/16(50.0%) 1/7(14.3%) 0.038
表3 Cox 回归分析乳腺癌的预后预后因素
因素 Wald df P值 RR
肿瘤大小
　　T1 9.41 3 0.02 1.000
　　T2 4.551 1 0.03 2.588
　　T3 5.406 1 0.02 3.013
　　T3 4.106 1 0.04 3.469
淋巴结转移
　　N0 11.264 2 0.003 1.000
　　N1 7.755 1 0.005 4.141
　　N2 10.941 1 0.001 5.171
分期
　　Ⅰ 13.872 2 0.001 1.000
　　Ⅱ 9.400 1 0.002 3.680
　　Ⅲ 11.651 1 0.001 8.077
ER 3.891 1 0.044 2.330
HER-2 1.222 1 0.027 1.616
MT1-MMP
　　- 6.513 2 0.037 1.000
　　+～ 3.761 1 0.045 2.332
　　 5.114 1 0.025 3.050
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