Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions

Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions
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DOI:
10.14670/hh-21.603
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发表时间:
2006-06-01
影响因子:
2
通讯作者:
Agnantis, NJ
Agnantis, NJ
中科院分区:
生物学4区
文献类型:
--
作者:
Peschos, D;Damala, C;Agnantis, NJ

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基质金属蛋白酶(matrix metalloproteinases,MMPs)是一类含锌的蛋白水解酶,在病理和生理条件下负责细胞外基质成分的降解。它们参与基底膜破坏、基质和血管渗透、转移,并且最近有证据表明它们参与肿瘤生长和血管生成事件。基质金属蛋白酶2和9(matrix metalloproteinase 2 and 9,MMP 2和9)属于明胶酶,是基质金属蛋白酶的一个亚类,具有降解基底膜基底层三螺旋IV型胶原的能力。在本研究中,我们试图通过免疫组织化学方法比较显示MMP-9在喉良性、癌前病变和恶性病变中的表达。我们研究了154例喉病变,包括55例鳞状细胞癌,8例原位癌,54例不典型增生(低度和中度),13例乳头状瘤和24例角化病。MMP 9在浸润性鳞癌和原位鳞癌中的阳性表达率分别为74.4%和50%。在异型增生的情况下,在乳头状瘤和角化病的过度表达的百分比分别为62.9%,61.53%和54.16%,MMP-9的表达是显着较高的浸润性鳞状细胞癌相比,异型增生(p=0.000004)。与乳头状瘤相比,异型增生病例中MMP-9的表达也显著更高(p=0.023)。MMP-9的表达既不相关的生存,也没有其他可用的临床病理参数(肿瘤大小,分级,临床分期,淋巴结状态和患者年龄)。总之,我们的研究表明,MMP-9的表达上调,在一个逐步的方式,有两个主要步骤,第一个,当发育不良病变演变和下一个,当发育不良进展到浸润性癌。
The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma.