乙酰肝素酶和MMP-9在胰腺癌中的表达及临床意义

Expression and Significance of Heparanase and MMP-9 in Pancreatic Carcinoma

目的:检测乙酰肝素酶(heparanase,HPA)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)在胰腺癌、慢性胰腺炎、正常胰腺组织中的表达及相互关系,分析其与浸润转移的关系。方法:应用免疫组化SP法检测92例胰腺癌、24例慢性胰腺炎和10例正常胰腺组织中HPA、MMP-9的表达水平,分析两者的表达与临床病理指标的关系,建立Spearman等级相关分析。结果:HPA在胰腺癌中表达明显高于慢性胰腺炎和正常胰腺组织(P<0.05),HPA阳性表达与周围组织浸润、淋巴结转移呈正相关(P<0.05),与性别、年龄及组织学分级无统计学相关(P>0.05);胰腺癌组织中MMP-9表达明显高于慢性胰腺炎和正常胰腺组织(P<0.05)。且MMP-9阳性表达与周围组织浸润、远处转移正相关(P<0.05),与性别、年龄、组织学分级无统计学相关(P>0.05)。HPA与MMP-9有较高的共同阳性表达率。HPA和MMP-9表达呈正相关(P<0.05),其共同表达率与肿瘤对周围脏器浸润和淋巴结转移有相关(P<0.05)。多因素分析显示HPA和MMP-9均非影响预后的独立因素。结论:HPA、MMP-9在胰腺癌组织中的表达可能与胰腺癌浸润、转移相关,可作为新的胰腺癌标记物用于联合检测,具有重要的临床意义。且MMP-9可能上调HPA表达水平,促进HPA介导的肿瘤浸润转移。

Objective： To investigate the expression of heparanase （HPSE） and matrix metalloproteinase-9 （MMP-9） in pancreatic carcinoma, chronic pancreatitis, normal pancreatic tissue and the correlation between the two, and to analyze the relationship among the proteins, the infiltration, and metastasis of pancreatic carcinoma. Methods： Immunohistochemi- cal staining （SP method） was used to measure the HPSE and MMP-9 expressions in 92 cases with pancreatic carcinoma, 24 with chronic pancreatitis （CP） and 10 with normal pancreatic tissue samples. The correlation between the expression of HPSE and MMP-9 and the clinico-pathologic index was analyzed and Pearson rank correlation analysis was set up for statistical treatment. Results： The expression of HPSE was significantly higher in pancreatic carcinoma than in chronic pancre- atitis and normal pancreatic tissue （P〈0.05）. The positive expression of HPSE protein had a positive correlation with the infiltration of peripheral tissue and lymph node metastasis （P〈0.05）, and had a negative correlation with the gender, age and histological grading （P〉0.005）. The expression of MMP-9 was significantly higher in the pancreaticcarcinoma than in the chronic pancreatitis and normal pancreas （P〈0.05）. The positive expression of MMP-9 protein positively correlated with the infiltration of peripheral tissue and the distant metastasis （P〈0.05）, and correlated negatively with the sex, age, and tumor differentiation of patients （P〉0.005）. Both HPSE and MMP-9 had a positive co-expression rate in pancreatic carcinoma. The expressions of HPSE correlated positively with that of MMP-9 in pancreatic carcinomas （P〈0.05）. The co-expression rate related to the tumor infiltration of other peripheral organs and nodal metastases （P〈0.05）. Multivariate analysis showed that neither HPSE nor MMP-9 were independent prognostic factors. Conclusion： HPSE and MMP-9 expression in pancreatic carcinoma may be associated with the infiltration and metastasis of carcinoma. These should be regarded as the new markers of pancreatic carcinoma for combined detection, with important clinical significance. MMP-9 may also up-regulate the level of HPSE expression, and facilitate the HPSE-mediated tumor infiltration and metastasis.