摘要
目的观察RECK (reversion inducing cysteine rich protein with kazal motifs)及MMP-9 (matrix metalproteinase 9)在胰腺癌组织中的表达,探讨RECK及MMP-9表达与胰腺癌临床病理特征的关系。
方法选择青岛大学医学院附属医院病理科临床病理资料齐全的胰腺癌组织蜡块标本28例,正常胰腺组织标本10例,采用免疫组化PV6000法检测胰腺癌及正常胰腺组织中RECK、MMP-9的表达情况,应用SPSS13.0进行统计学处理,采用χ2检验、fisher确切概率法及spearman相关分析,以P<0.05认为有统计学差异。
结果RECK在28例胰腺癌组织中的阳性表达率为46.43%,在10例正常胰腺组织中的阳性表达率为90%,两者之间的差异显著(P<0.05)。RECK在胰腺癌组织中的表达与胰腺癌患者的性别、年龄、肿瘤大小、肿瘤部位、分化程度间无显著差异(P均>0.05),而肿瘤临床分期为Ⅰ+Ⅱ组的RECK阳性表达率明显高于Ⅲ+Ⅳ期组(P<0.05),无远处转移组的RECK阳性表达率明显高于有远处转移组(P<0.05)。MMP-9在28例胰腺癌组织中的阳性表达率为75%,在10例正常胰腺组织中的阳性表达率为20%,两者之间有显著差异(P<0.01)。MMP-9在胰腺癌组织中的表达与患者的性别、年龄、肿瘤大小、肿瘤部位、淋巴结转移及远处转移之间无显著差异(P>0.05),而肿瘤临床分期为Ⅰ+Ⅱ期组的MMP-9阳性表达率明显低于Ⅲ+Ⅳ期组(P<0.05),肿瘤高分化组的MMP-9阳性表达率明显低于低分化组(P<0.01)。胰腺癌组织中RECK与MMP-9的表达呈负相关(r=-0.536,P<0.01)。
结论胰腺癌组织中RECK呈低表达,MMP-9呈高表达,RECK、MMP-9联合检测可以作为临床分期评估的重要指标。
Objective:To investigate the expression of RECK and MMP-9 in pancreatic cancer and to explore the relationship between RECK or MMP-9 expression and the clinical pathological characteristic.
Methods:The specimens were provided by the Department of Pathology, the Affiliated Hospital of Medical College, Qingdao University. It contained 28 cases of pancreatic cancer and 10 cases of normal pancreatic tissue. Each case had complete clinical pathological information. PV6000 immunohistochemical method was used to detect the expression of RECK and MMP-9 in pancreatic cancer and normal pancreatic tissue. All the statistical analyses were performed using SPSS 13.0 statistical software, including x 2 test,fisher exact test and spearman correlation analysis. The value p<0.05 was accepted as the level of significance.
Results:The overall positive rate of RECK was 46.43% in pancreatic cancer, and 90% in normal pancreatic tissue. The comparison between these two groups indicated a significant difference (P<0.05). No statistically significant correlation was found with age, gender, tumor size, tumor locus and tumor differentiation (P>0.05).However, the positive rate of RECK inⅠ+Ⅱstage(tumor stage) was significantly higher than in III+IV stage(P<0.05). The positive rate of RECK in cases with distant metastases was significantly higher than in cases without distant metastasis(P<0.05). The overall positive rate of MMP-9 was 75% in pancreatic cancer, and 20% in normal pancreatic tissue. The comparison between these two groups indicated a significant difference (P<0.01). No statistically significant relationship was found with age, gender, tumor size, tumor locus, lymph node involvement and distant metastases (P>0.05). However, the positive rate of MMP-9 inⅠ+Ⅱstage(tumor stage) was significantly lower than inⅢ+Ⅳstage(P<0.05). The positive rate of MMP-9 in high differentiation (tumor differentiation) was significantly lower than in low differentiation (P<0.01). The expression of RECK was negatively correlated with the expression of MMP-9 (r=-0.536, P<0.01).
Conclusion:RECK is lowly expressed in pancreatic cancer, but MMP-9 is highly expressed. RECK and MMP-9 may serve as the important markers in the evaluation of tumor stage.
引文
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8 Miki T, takegami Y, Okawa K. The reversion-inducing cysteine-rich protein with Kazal Motifs (RECK) interacts with membrane type 1 matrix metalloproteinase and CD13/aminopeptidase N and modulates their endocytic pathways[J]. J. Biol. Chem,2007,282(16):12341-12352.
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14张勇,郑启昌,卢昕,等.肿瘤抑制基因RECK在胃癌中的表达及临床意义[J].肿瘤防治杂志,2005；12(2)：110-113.
15 Furumoto K, Arii S, Mori A, et al. RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance [J]. Hepatology,2001; 33(1):189-195.
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39 lllemann M, Bird N, Majeed A, et al. MMP-9 is differentially expressed in primary human colorectal adenocarcinomas and their metastases[J]. Mol Cancer Res,2006,4(5):293-302.
40 Yu HZ, Li ZP, Li SG, et al. Correlations of serous levels of matrix metalloproteinases (MMP-2 and MMP-9) to invasion and metastasis of papillary thyroid carcinoma[J]. Ai Zheng,2005,24(6):740-742.
41 Chen XL, Wang LC, Zhang WG, et al. Correlations of S100A4 and MMP-9 expressions to infiltration, metastasis and prognosis of non-small cell lung cancer[J]. Nan Fang Yi Ke Da Xue Xue Bao,2008,28(7):1254-1258.
42胡忠良,文继舫,沈明等TGIF, MMP9和VEGF蛋白在胃癌中的表达及临床病理联系[J].中南大学学报(医学版),2006,31(1)：70-74.
43 钟崇,郭荣平,石明等VEGF与MMP-9在肝癌组织中的表达及其临床意义[J].癌症,2006,25(5)：599-603.
44 Nagakawa Y, AOKI T,KASUYA K,et al.Histologic features of venous invasion, expression of Vascular endothelial growth factor and matrix metalloproteinase-2 and matrix metalloproteinase-9, and the relation with liver metastasis in pancreatic cancer[J]. Pancreas,2002,24:169.
45 Maatta M, Soini Y, Liakka A, et al. Differential Expression of Matrix Metalloproteinase (MMP)-2, MMP-9, and Membrane Type 1-MMP in Hepatocellular and Pancreatic Adenocarcinoma:Implications for Tumor Progression and Clinical Prognosis[J]. Clinical Cancer Research,2000,6:2726-2734.
46 Pryczynicz A, Ustymowicz KG, Piekarska VD, et al. Expression of matrix metalloproteinase 9 in pancreatic ductal carcinoma is associated with tumor metastasis formation[J]. Folia Histochemica Et Cytobiologica,2007,45:37-40.
47 Parsons SL, Watson SA, Collins HM, et al. Gelatinase (MMP-2 and 9) expression in gastrointestinal malignancy[J]. Br J Cancer,1998; 78:1495-1502.
48 Noda M, Oh J, Takahashi R, Kondo S, et al. RECK:a novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodel ing [J]. Cancer Metastasis Rev,2003; 22:167-175。