Milovanovic J, Todorovic-Rakovic N, Abu Rabi Z
Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
J BUON. 2013 Oct-Dec;18(4):866-73.
To investigate the relationships, if any, between interleukin (IL) -8/matrix metalloproteinase (MMP)-2/ MMP-9 and other prognostic variables in lymph node-negative untreated breast cancer patients, and to determine the prognostic value of these potential biomarkers.
The study included 135 patients with known clinicopathological parameters. IL-8, MMP-2 and MMP-9 levels were determined by ELISA in primary tumor tissue lysates.
There were no significant relationships between IL-8/MMP-2/MMP-9 expression and available clinicopathological parameters (patient age, menopausal status, tumor size and tumor grade). Estrogen receptor (ER)- patients had higher levels of both IL-8 and MMP-9 (p=0.006 and p=0.04, respectively) compared to ER+ patients; there was a significant negative correlation between ER and IL-8 (p=0.02). MMP-9 expression was significantly higher in patients with higher levels of IL-8 (p<0.001) and there was a significant positive correlation between IL-8 and MMP-9, as well as between progesterone receptor (PR) and MMP-2 (p<0.001 and p=0.05, respectively). PR+ patients had higher levels of MMP-2 than PR- patients (p=0.03). Among the investigated biomarkers, only IL-8 had a statistically significant prognostic value in terms of relapse free survival (RFS) (p<0.001). Patients with higher levels of IL-8 had worse prognosis.
Expression of IL-8 and consequently expression of MMP-9 could be hormonally regulated in breast cancer. IL-8 could be a marker of more aggressive, ER- breast cancer phenotype. Different expression of MMP-2 and MMP-9 regarding differential hormonal receptor expression could indicate distinct mechanisms of their regulation. It seems that IL-8 is a strong and independent unfavorable prognostic parameter in node-negative breast cancer. Node-negative patients with higher levels of IL-8 should be treated with adjuvant, especially IL-8 targeted therapy.
研究白细胞介素（IL）-8/基质金属蛋白酶（MMP）-2/MMP-9与淋巴结阴性、未经治疗的乳腺癌患者其他预后变量之间的关系（若存在关系），并确定这些潜在生物标志物的预后价值。
该研究纳入了135例具有已知临床病理参数的患者。通过酶联免疫吸附测定法（ELISA）测定原发性肿瘤组织裂解物中的IL-8、MMP-2和MMP-9水平。
IL-8/MMP-2/MMP-9表达与可用的临床病理参数（患者年龄、绝经状态、肿瘤大小和肿瘤分级）之间无显著关系。与雌激素受体（ER）阳性患者相比，ER阴性患者的IL-8和MMP-9水平均较高（分别为p = 0.006和p = 0.04）；ER与IL-8之间存在显著负相关（p = 0.02）。IL-8水平较高的患者中MMP-9表达显著更高（p < 0.001），并且IL-8与MMP-9之间以及孕激素受体（PR）与MMP-2之间存在显著正相关（分别为p < 0.001和p = 0.05）。PR阳性患者的MMP-2水平高于PR阴性患者（p = 0.03）。在所研究的生物标志物中，就无复发生存期（RFS）而言，只有IL-8具有统计学上显著的预后价值（p < 0.001）。IL-8水平较高的患者预后较差。
乳腺癌中IL-8的表达以及由此导致的MMP-9的表达可能受激素调节。IL-8可能是侵袭性更强的ER阴性乳腺癌表型的标志物。MMP-2和MMP-9在激素受体表达差异方面的不同表达可能表明其调节机制不同。似乎IL-8是淋巴结阴性乳腺癌中一个强大且独立的不良预后参数。IL-8水平较高的淋巴结阴性患者应接受辅助治疗，尤其是IL-8靶向治疗。
