Matrix metalloproteinases expression correlates with survival in patients with esophageal squamous cell carcinoma
Matrix metalloproteinases expression correlates with survival in patients with esophageal squamous cell carcinoma
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DOI：
10.1111/j.1572-0241.2005.50018.x
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发表时间：
2005-08-01
影响因子：
9.8
通讯作者：
Chen, KN
中科院分区：
文献类型：
--
作者：
Gu, ZD;Li, JY;Chen, KN
目的：基质金属蛋白酶（matrix metalloproteinases，MMPs）是一类锌依赖性内肽酶，能够降解细胞外基质，在恶性肿瘤中发挥重要作用。我们评估了四种基质金属蛋白酶在食管鳞状细胞癌（ESCC）的表达，并评估MMP表达与临床病理特征和无病生存期之间的关系。方法：我们评估了MMP 1，MMP 7，MMP 9和MMP 13在208例ESCC患者的组织中的表达，采用免疫组化（IHC），并将MMP表达与临床病理特征和无病生存期相关。结果：208例食管鳞癌组织中MMP 1、MMP 7、MMP 9和MMP 13的阳性率分别为63.0%、41.8%、49.0%和32.2%。MMPs在癌细胞胞浆中呈强阳性表达，尤其在浸润边缘，而在间质细胞中呈弱阳性表达。非癌食管粘膜中未检测到免疫染色。MMP 9表达与肿瘤细胞分化差（p= 0.001）、血管渗透（p= 0.027）和淋巴结转移（p= 0.027）呈正相关。MMP 9表达是无病生存时间的负性独立预测因子（风险比，1.470; 95%CI，1.105与1.955相似; p= 0.008）。MMP 7（MMP 7阳性患者的中位生存期为23个月，MMP 7阴性患者的中位生存期为> 77个月; p= 0.001）和MMP 13（MMP 13阳性患者的中位生存期为18个月，MMP 13阴性患者的中位生存期为39个月; p= 0.014）的表达与相对早期ESCC患者的无病生存期呈负相关。MMP 7、MMP 9和MMP 13在相对早期的ESCC样本中的共表达鉴定了预后不良的患者（13个月的中位生存时间）与缺乏MMP 7、MMP 9和MMP 13表达的患者相比（58个月的中位生存时间，p < 0.001）。MMP 9表达是食管鳞癌的一个负性、独立的预后因素，与肿瘤细胞分化、血管浸润和淋巴结转移相关。MMP 7、MMP 9和MMP 13可能在早期ESCC中起作用，并且它们的共表达预测相对早期ESCC患者的不良结局。
OBJECTIVES: The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases capable of degrading the extracellular matrix and play important roles in malignancies. We evaluated the expression of four MMPs in esophageal squamous cell carcinoma (ESCC), and assessed the association between MMP expression and clinicopathologic characteristics and disease-free survival time.METHODS: We evaluated MMP1, MMP7, MMP9, and MMP13 expression in tissues from 208 patients with ESCC using immunohistochemistry (IHC), and correlated MMP expression to clinicopathologic characteristics and disease-free survival time. To confirm MMP9 expression at different levels, we simultaneously performed RT-PCR, Western blotting, and IHC on tissues from a separate cohort of 23 patients with ESCC.RESULTS: IHC analysis showed that 63.0%, 41.8%, 49.0%, and 32.2% of 208 ESCC samples were positive for MMP1, MMP7, MMP9, and MMP13, respectively. MMPs were strongly expressed in the cytoplasm of cancer cells, especially in the invasive margin, and weakly expressed in stromal cells. No immunostaining was detected in non-cancerous esophageal mucosa. MMP9 expression was positively associated with poor tumor cell differentiation (p= 0.001), vessel permeation (p= 0.027), and lymph node metastasis (p= 0.027). MMP9 expression was a negative, independent predictor of disease-free survival time (Hazard ratio, 1.470; 95% CI, 1.105 similar to 1.955; p= 0.008). The expression of MMP7 (median survival time: 23 months for MMP7 positive patients, > 77 months for MMP7 negative patients; p= 0.001) and MMP13 (median survival time: 18 months for MMP13 positive patients, 39 months for MMP13 negative patients; p= 0.014) correlated negatively with disease-free survival in relatively early stage ESCC patients. Co-expression of MMP7, MMP9, and MMP13 in relatively early stage ESCC samples identified patients with a poor prognosis (13 months median survival time) compared to those lacking MMP7, MMP9, and MMP13 expression (58 months median survival time, p < 0.001).CONCLUSIONS: MMP9 expression is a negative, independent prognostic factor in ESCC and correlates with tumor cell differentiation, vessel permeation, and lymph node metastasis. MMP7, MMP9, and MMP13 may function in early stage ESCC, and their co-expression predicts poor outcome for relatively early stage ESCC patients.