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基质金属蛋白酶-2(MMP-2)与接受抗雌激素辅助治疗的绝经后淋巴结阳性乳腺癌患者的复发风险相关。

Matrix metalloproteinase-2 (MMP-2) is associated with the risk for a relapse in postmenopausal patients with node-positive breast carcinoma treated with antiestrogen adjuvant therapy.

作者信息

Talvensaari-Mattila A, Pääkko P, Blanco-Sequeiros G, Turpeenniemi-Hujanen T

机构信息

Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Finland.

出版信息

Breast Cancer Res Treat. 2001 Jan;65(1):55-61. doi: 10.1023/a:1006458601568.

Abstract

Node-positive breast carcinoma is an aggressive disease. Postmenopausal patients benefit from antiestrogen adjuvant therapy. Predictive markers could, however, be useful in selecting these patients for different modalities of adjuvant therapy. Recently, we showed that MMP-2 (72 kD type IV collagenase/gelatinase A) is correlated with unfavorable prognosis in premenopausal breast carcinoma patients. Expression of the immunoreactive protein for MMP-2 was evaluated prospectively in this study in paraffin tissue sections from primary tumors of 100 postmenopausal, node-positive breast carcinoma patients treated with an adjuvant antiestrogen therapy. A specific MMP-2 monoclonal antibody in an avidin-biotin immunohistochemical staining was used. Sixty nine percent of the samples were MMP-2 positive. Eighty three percent of the MMP-2 negative patients lived for 5 years without a recurrence, while only 67% of the patients with an MMP-2 positive primary tumor were recurrence-free at that time (p < 0.05; log rank analysis). MMP-2 positivity showed a significant correlation with shortened survival in patients with a small primary tumor (T1-2) and a low axillary tumor burden. One hundred percent of these patients with an MMP-2 negative breast carcinoma survived for 5 years, compared to 73% of the MMP-2 positive cases alive at that time (p = 0.02). In conclusion, we show here that MMP-2 is a prognostic indicator in postmenopausal patients with node-positive breast carcinoma with a low tumor burden, and that it predicts a risk for failure in antiestrogen adjuvant therapy. It might have predictive value in selecting the most efficient adjuvant therapy in this set of patients.

摘要

淋巴结阳性乳腺癌是一种侵袭性疾病。绝经后患者可从抗雌激素辅助治疗中获益。然而,预测性标志物可能有助于为这些患者选择不同的辅助治疗方式。最近,我们发现基质金属蛋白酶-2(72 kD IV型胶原酶/明胶酶A)与绝经前乳腺癌患者的不良预后相关。在本研究中,我们对100例接受辅助抗雌激素治疗的绝经后淋巴结阳性乳腺癌患者原发肿瘤的石蜡组织切片进行了前瞻性评估,以检测基质金属蛋白酶-2免疫反应蛋白的表达。采用抗生物素蛋白-生物素免疫组织化学染色中的一种特异性基质金属蛋白酶-2单克隆抗体。69%的样本基质金属蛋白酶-2呈阳性。基质金属蛋白酶-2阴性患者中有83%存活5年无复发,而原发肿瘤基质金属蛋白酶-2阳性的患者此时只有67%无复发(p<0.05;对数秩分析)。在原发肿瘤较小(T1-2)且腋窝肿瘤负荷较低的患者中,基质金属蛋白酶-2阳性与生存期缩短显著相关。这些基质金属蛋白酶-2阴性乳腺癌患者中有100%存活5年,而此时基质金属蛋白酶-2阳性病例中有73%存活(p = 0.02)。总之,我们在此表明,基质金属蛋白酶-2是肿瘤负荷较低的绝经后淋巴结阳性乳腺癌患者的预后指标,并且它可预测抗雌激素辅助治疗失败的风险。在选择这组患者中最有效的辅助治疗方面,它可能具有预测价值。

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