Zhou Cai-yun, Yao Ji-fen, Chen Xiao-duan
Woman's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, P. R. China.
Ai Zheng. 2002 Jul;21(7):735-9.
BACKGROUND & OBJECTIVE: Studies of tumor invasion and metastasis have focused on the degradation of extracellular matrix (ECM). Matrix metalloproteinases (MMPs), which could degrade ECM, were implicated in cancer invasion and metastasis. Activated MMPs were controlled by specific tissue inhibitors of metalloproteinases (TIMPs). This study was designed to investigate the expression of MMP-2, MMP-9 and TIMP-1, TIMP-2 in human squamous cell carcinomas of uterine cervix, and the association with invasion and metastasis of human squamous cell carcinoma of uterine cervix.
Tissue samples from 40 cases of squamous cell carcinoma of the uterine cervix, 29 cases of cervical intraepithelial neoplasia (CIN), and 16 cases of normal cervices were stained immunohistochemically.
Immunohistochemical staining of tumor cells for MMP-2, MMP-9, TIMP-1, and TIMP-2 were noted 82.5%, 70.0%, 62.5%, and 97.5% in carcinomas, 44.8%, 62.1%, 86.21%, and 96.55% in CIN lesions respectively, for MMP-2, MMP-9, TIMP-1 in 25.0% normal cervices, but for TIMP-2 in 56.25% normal cervices. There was significant difference for MMP-2 among carcinomas, normal cervices, and CIN respectively (P < 0.01). There was significant difference for MMP-9 among normal cervices, carcinomas, and CIN, respectively (P < 0.05). The positive rates of TIMP-1 and TIMP-2 in the cervical carcinoma group and CIN group were obviously higher than that in normal cervical group(P < 0.01). The positive rates of MMP-2 and MMP-9 in lymph node metastasis were obviously higher than that in without lymph node metastasis(P < 0.01), but for TIMP-2 was contrary and there was no significant difference for TIMP-1. No significant correlation could be established among the expression of these markers and the tumor diameter, the clinical stage, and pathologic grade.
The over-expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 may play a key role in invasion and lymph-node metastasis of in squamous carcinoma of the cervix.
肿瘤侵袭和转移的研究主要集中在细胞外基质(ECM)的降解。基质金属蛋白酶(MMPs)能够降解ECM,与癌症的侵袭和转移有关。活化的MMPs受金属蛋白酶特异性组织抑制剂(TIMPs)的调控。本研究旨在探讨基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)以及金属蛋白酶组织抑制剂-1(TIMP-1)、金属蛋白酶组织抑制剂-2(TIMP-2)在子宫颈鳞状细胞癌中的表达及其与子宫颈鳞状细胞癌侵袭和转移的关系。
采用免疫组织化学方法对40例子宫颈鳞状细胞癌组织、29例宫颈上皮内瘤变(CIN)组织及16例正常宫颈组织进行检测。
MMP-2、MMP-9、TIMP-1、TIMP-2在子宫颈鳞状细胞癌中的阳性表达率分别为82.5%、70.0%、62.5%、97.5%;在CIN中的阳性表达率分别为44.8%、62.1%、86.21%、96.55%;MMP-2、MMP-9、TIMP-1在正常宫颈组织中的阳性表达率分别为25.0%、TIMP-2为56.25%。MMP-2在子宫颈鳞状细胞癌、正常宫颈组织及CIN之间差异有统计学意义(P<0.01);MMP-9在正常宫颈组织、子宫颈鳞状细胞癌及CIN之间差异有统计学意义(P<0.05)。子宫颈癌组和CIN组TIMP-1和TIMP-2的阳性率明显高于正常宫颈组(P<0.01)。有淋巴结转移组MMP-2和MMP-9的阳性率明显高于无淋巴结转移组(P<0.01),TIMP-2则相反,TIMP-1差异无统计学意义。这些指标的表达与肿瘤直径、临床分期及病理分级之间无明显相关性。
MMP-2、MMP-9、TIMP-1和TIMP-2的过表达可能在子宫颈鳞状细胞癌的侵袭及淋巴结转移中起关键作用。