宫颈癌MMP-9表达与肿瘤血管生成、癌细胞增殖及侵袭转移的关系

Relationship between Expression of Matrix Metalloproteinase (MMP-9)and Tumor Angiogenesis,Cancer Cell Proliferation,Invasion,and Metastasis in Invasive Carcinoma of Cervix

背景和目的:基质金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)在肿瘤血管生成及肿瘤侵袭转移过程中起重要调节作用。本研究探讨MMP-9在早期宫颈癌的表达和临床意义。方法:采用免疫组织化学SP法检测75例早期宫颈浸润癌(invasivecarcinomaofcervix,ICC)、18例宫颈上皮内瘤样病变(cervicalintraepithelialneoplasm,CIN)和15例正常宫颈上皮(normalcervicalepithelium,NCE)中MMP-9的表达情况,并检测其微血管密度(microvesseldensity,MVD)(CD34标记)和癌细胞增殖标记指数(Ki-67标记)。结果:在宫颈癌中,MMP-9主要表达于癌细胞膜和/或细胞浆;Ki-67主要表达于癌细胞核;CD34主要表达于间质血管内皮细胞。从正常宫颈上皮到宫颈上皮内瘤样病变再到宫颈浸润癌,MMP-9、Ki-67的阳性表达率和MVD均逐步显著升高(P<0.05)。MMP-9在ICC中表达与MVD显著正相关(r=0.287,P<0.05)。MMP-9在ICC中表达与盆腔淋巴结转移、脉管浸润、间质浸润、FIGO分期、组织学分级和Ki-67表达有关(P<0.05或P<0.01);而与年龄和组织学类型无关(P>0.05)。有盆腔淋巴结转移、脉管浸润、突破深层间质浸润、FIGO分期为Ⅱ期、组织学分级为Ⅲ级及Ki-67高度表达者,其MMP-9阳性表达率分别显著高于无盆腔淋巴结转移、无脉管浸润、浸润深度在浅层间质以内。

BACKGROUND & OBJECTIVE:Matrix metalloproteinase 9 (MMP 9) might plays an important role in regulating processes of tumor angiogenesis, invasion,and metastasis. The expression and clinical significance of MMP 9 in early invasive carcinoma of cervix was investigated. METHODS:Expression of MMP 9, microvessel density (MVD) labeled by CD34 and proliferation index of cancer cells labeled by Ki 67 in 75 cases of early invasive carcinoma of cervix (ICC), 18 cases of cervical intraepithelial neoplasm (CIN), and 15 cases of normal cervical epithelium (NCE) were detected by immunohistochemistry SP method. RESULTS:MMP 9 was mainly expressed in the cellular membrane and/or cytoplasm in tumor cells,whereas expression of Ki 67 was mainly confined to the nuclei, and that of CD34,to the vascular epithelial cells in tumor stroma. It was shown that positive rate of expression of MMP 9,Ki 67,and MVD increased remarkably from NCE to CIN,and then to ICC accordingly(P< 0 05). In ICC,MVD was positively related to the expression of MMP 9 (r=0 287, P< 0 05). The expression of MMP 9 correlated with pelvic lymph node metastasis,intravascular and stromal infiltration, FIGO staging, histological grading,and Ki 67 expression (P< 0 05 or P< 0 01); but not correlated with patients age and histological types (P >0 05). In cases with pelvic lymph node metastasis,intravascular and deeper stroma infiltration,FIGO staging Ⅱ,histological grade Ⅲ and over expression of Ki 67,positive rate of expression of MMP 9 was significantly higher than that in those without the conditions mentioned above (P< 0 05). CONCLUSION:In cervical carcinoma, MMP 9 may play an important role during tumor angiogenesis, proliferation of cancer cells, cancer invasion and metastasis. Over expression of MMP 9 may result in great increase of tumor angiogenesis, rapid proliferation of cancer cells, cancer invasion and metastasis, but it is not the only decisive factor. Detection expression of MMP 9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.