Talvensaari-Mattila A, Pääkkö P, Turpeenniemi-Hujanen T
Department of Obstetrics and Gynecology, PO Box 5000, 90014, University of Oulu, Oulu, Finland.
Br J Cancer. 2003 Oct 6;89(7):1270-5. doi: 10.1038/sj.bjc.6601238.
Adjuvant therapy is one of the major advances in the treatment of breast carcinoma patients - but do all patients need it? New predictive markers, which are able to save breast carcinoma patients from the most toxic adjuvant therapies, are still needed. The expression of matrix metalloproteinases (MMP-2) has been previously linked to invasiveness of carcinoma cells. In this study, we explored the role of MMP-2 as a prognostic factor in breast carcinoma in a large series to be able to show the favourable effect of MMP-2 negativity in poor prognosis subgroup of hormone receptor-negative patients. The MMP-2 immunoreactive protein was evaluated from primary adenocarcinoma of the breast in 453 cases by using a specific monoclonal antibody in immunohistochemical stainings. The MMP-2 protein found in breast carcinoma tumour cells was here shown to be associated with a shortened recurrence-free survival or relative overall survival (P=0.03). It was shown here that MMP-2 negativity is significantly linked to favourable prognosis in patients considered to be at risk due to their hormone receptor negativity. In the patient group presenting with a progesterone receptor-negative tumour, the survival rate of the MMP-2-positive cases was 58% while it was 95% in MMP-2-negative cases after 10 years of follow-up (P=0.005). The present data shows for the first time that MMP-2 negativity could serve as a marker for favourable prognosis in breast carcinoma patients with a hormone receptor-negative tumour usually associated with high risk. MMP-2 is also shown to correlate to shortened survival independent of major prognostic indicators in patients with primary breast carcinoma.
辅助治疗是乳腺癌患者治疗的重大进展之一，但所有患者都需要它吗？仍需要新的预测标志物，以便让乳腺癌患者免受毒性最强的辅助治疗。基质金属蛋白酶（MMP - 2）的表达先前已与癌细胞的侵袭性相关联。在本研究中，我们在一个大型队列中探讨了MMP - 2作为乳腺癌预后因素的作用，以便能够显示MMP - 2阴性在激素受体阴性患者预后不良亚组中的有利影响。通过在免疫组织化学染色中使用特异性单克隆抗体，对453例乳腺原发性腺癌中的MMP - 2免疫反应蛋白进行了评估。结果显示，乳腺癌肿瘤细胞中发现的MMP - 2蛋白与无复发生存期缩短或相对总生存期缩短相关（P = 0.03）。研究表明，对于因激素受体阴性而被认为处于风险中的患者，MMP - 2阴性与良好的预后显著相关。在出现孕激素受体阴性肿瘤的患者组中，随访10年后，MMP - 2阳性病例的生存率为58%，而MMP - 2阴性病例为95%（P = 0.005）。本数据首次表明，MMP - 2阴性可作为激素受体阴性肿瘤通常与高风险相关的乳腺癌患者预后良好的标志物。在原发性乳腺癌患者中，MMP - 2还显示出与独立于主要预后指标的生存期缩短相关。
