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基质金属蛋白酶-2在子宫颈癌中的临床意义:利用组织芯片对免疫反应性进行的半定量研究

Clinical significance of matrix metalloproteinase-2 in cancer of uterine cervix: a semiquantitative study of immunoreactivities using tissue array.

作者信息

Wang Po-Hui, Ko Jiunn-Liang, Tsai Hsiu-Ting, Yang Shun-Fa, Han Chih-Ping, Lin Long-Yau, Chen Gin-Den

机构信息

Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, 110, Section 1, Chien-Kuo North Road, Taichung, 40201, Taiwan.

出版信息

Gynecol Oncol. 2008 Mar;108(3):533-42. doi: 10.1016/j.ygyno.2007.11.018. Epub 2008 Jan 4.

Abstract

OBJECTIVES

To study the expression of matrix metalloproteinase-2 (MMP-2) in cancer of uterine cervix and correlate its expression with clinicopathological parameters, recurrence and survival of patients.

METHODS

Twenty cervical cancer and 20 normal tissues from the same patients were collected to detect MMP-2 mRNA expression. From them, 16 cancer and 16 normal tissues were collected and added with another 64 cancer tissues to construct a 96-tissue core microarray for immunohistochemical study. We evaluated the relationships among MMP-2 immunoreactivity using semiquantitative H scores, obtained by multiplying proportion score of stained cells and their mean digital density, and clinicopathological variables, recurrence and survival in cervical cancer patients. We used univariate and multivariate analyses of all parameters for recurrence and survival, further including time interval for evaluation.

RESULTS

MMP-2 mRNA expression was higher in most of cervical cancerous tissues than normal counterparts. H score of MMP-2 was significantly higher in cancerous tissue cores than normal counterparts (median H scores: 1.5 vs. 0.3, P<0.001). MMP-2 expression was significantly associated with parametrium invasion (P=0.004) and lymph node metastasis (P=0.015), but not with cancer recurrence, recurrence-free and overall survival rates of these patients. However, poor tumor cell differentiation and positive parametrium invasion significantly increased the recurrence and poor cell differentiation increased the risk of death.

CONCLUSIONS

MMP-2 is highly expressed in cervical cancer tissues at mRNA and protein levels and associated with lymph node metastasis and parametrium invasion but not predictive of recurrence and survival in cervical cancer patients.

摘要

目的

研究基质金属蛋白酶-2(MMP-2)在子宫颈癌中的表达,并将其表达与患者的临床病理参数、复发及生存情况相关联。

方法

收集20例子宫颈癌患者的癌组织及同一患者的20例正常组织,检测MMP-2 mRNA表达。从中选取16例癌组织和16例正常组织,并另取64例癌组织构建96组织芯微阵列进行免疫组织化学研究。我们使用半定量H评分评估MMP-2免疫反应性与临床病理变量、子宫颈癌患者复发及生存情况之间的关系,H评分通过将染色细胞的比例评分与其平均光密度相乘获得。我们对所有复发和生存参数进行单因素和多因素分析,进一步包括评估的时间间隔。

结果

大多数子宫颈癌组织中MMP-2 mRNA表达高于正常对照。癌组织芯中MMP-2的H评分显著高于正常对照(中位数H评分:1.5对0.3,P<0.001)。MMP-2表达与宫旁组织浸润(P=0.004)和淋巴结转移(P=0.015)显著相关,但与这些患者的癌症复发、无复发生存率和总生存率无关。然而,肿瘤细胞分化差和宫旁组织浸润阳性显著增加复发风险,细胞分化差增加死亡风险。

结论

MMP-2在子宫颈癌组织中mRNA和蛋白水平均高表达,与淋巴结转移和宫旁组织浸润相关,但不能预测子宫颈癌患者的复发和生存情况。

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