早期乳腺癌血清MMP-2水平与外周血循环肿瘤细胞的相关性及临床意义

Serum level of MMP-2 in early breast cancer and its correlation with circulating tumor cells

目的检测早期乳腺癌患者血清中基质金属蛋白酶2（MMP-2）及细胞角蛋白19（CK19）的表达水平，探讨二者的相互关系及临床意义。方法应用ELISA法分别检测10例乳腺纤维腺瘤患者及72例乳腺癌患者血清中MMP-2的水平，同时应用实时定量反转录-聚合酶链反应方法检测相应患者外周血CK-19的表达水平，并进行相关性分析。结果MMP-2在乳腺癌患者血清中的表达水平为12．24μg／L，明显高于乳腺纤维腺瘤患者（2．21μg／L），二者差异有统计学意义（P=0．003）；在人表皮生长因子受体2（HER-2）阳性的乳腺癌患者中，血清MMP-2水平明显高于HER-2阴性患者（16．77μg/L与10．02μg／L，P=0．022）。CK19在乳腺纤维腺瘤患者外周血中未见表达，在乳腺癌患者外周血中，阳性表达30例（41．7％），在CK19阳性乳腺癌患者血清中，MMP-2水平为（15．48±2．02）μg／L，显著高于CK19阴性患者（7．16±1．55）μg／L（P=0．013）。结论早期乳腺癌患者血清MMP-2水平与外周血微转移密切相关，提示血清MMP-2的高表达可能是导致乳腺癌转移的因素之一。

Objective To explore the serum levels of MMP-2 in early breast cancer and its clinical significance and correlation with the circulating tumor cells in the patients. Methods The serum levels of MMP-2 in breast fibroadenoma （ n = 10 ） and breast cancer （ n = 72 ） were detected by enzyme-linked immunosorbent assay （ELISA）. And CK19 mRNA was measured by quantitative reverse transcription- polymerase chain reaction in blood as an index of circulating tumor cells in the patients. Results The serum level of MMP-2 in breast cancer was significantly higher than that in breast fibroadenoma （ 12. 24 vs 2. 21 p^g/L, P = 0. 003 ）. Subgroup analysis showed that the serum levels of MMP-2 were higher in HER-2 positive patients than those in HER-2 negative ones （ 16.77 vs 10. 02 Ixg/L, P =0. 022）. CK19 mRNA was found in blood samples from 30 cases of breast cancer and the positive rate was 41.7%. However, it was not detected in the patients with breast fibroadenoma. The mean levels of serum MMP-2 were （ 15.48 ± 2. 02） and （7.16 ± 1.55） p,g/L in CK19 positive and negative patients respectively. Significant difference existed between two groups （ P = 0.013）. Conclusion The serum level of MMP-2 in early breast cancer is closely correlated with blood micrometastasis. And its high level may be an important contributing factor for the metastasis of breast cancer .