胃癌组织中CEACAM6、MMP-9的表达及其临床病理意义
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摘要
目的：检测胃癌组织、癌旁组织及正常胃组织中癌胚抗原相关细胞粘附分子(CEACAM6)和基质金属蛋白酶9(MMP-9)的表达,分析CEACAM6、MMP-9与胃癌微血管生成及临床病理学的关系,探讨其在胃癌发生发展及血管生成中的作用及意义。
方法：用免疫组化法(Envision二步法)分别检测CEACAM6、MMP-9在54例胃癌组织、相应癌旁组织及20例手术切缘胃正常组织中的表达,并用Anti-factorⅧ标记血管,进行微血管计数。
结果：
1、CEACAM6在胃癌组织中的阳性表达率85.19%(46/54),明显高于相应癌旁组织40.74%(22/54)和手术切缘胃正常组织15%(3/20)(P<0.05),其表达与胃癌的浸润深度、临床分期明显相关(P<0.05),而与性别、年龄、组织类型、肿瘤部位、癌组织的分化程度和有无淋巴结转移无关(P>0.05)；
2、MMP-9在胃癌组织中的阳性表达率74.07%(40/54),较相应癌旁组织33.33%(18/54)及手术切缘胃正常组织10%(2/20)明显增高(P<0.05),其表达与肿瘤部位、癌组织的分化程度、有无淋巴结转移、浸润深度和临床分期相关(P<0.05),而与性别、年龄、组织类型无相关性(P>0.05)。
3、在胃癌组织中Anti-factorⅧ标记的微血管密度(MVD)值(32.17±8.97)明显高于相应癌旁组织(25.05±6.19)及手术切缘正常组织(18.62±5.07)(P<0.05),.其水平高低与肿瘤组织类型、肿瘤部位、癌组织的分化程度、有无淋巴结转移、浸润深度和临床分期相关(P<0.05),但与性别、年龄无关(P>0.05)。
4、CEACAM6与MMP-9在胃癌组织的表达呈正相关(r=0.593,P=0.000)。
5、CEACAM6阳性表达组和MMP-9阳性表达组的MVD值均高于其阴性表达组的MVD值(P<0.05)；且CEACAM6和MMP-9均为阳性表达的患者,其胃癌组织MVD值(33.16±9.38)高于CEACAM6和MMP-9均为阴性表达的患者(15.07±9.31),也高于CEACAM6阳性表达、MMP-9阴性表达的患者(22.95±3.99),差异均有统计学意义(P<0.05)。
结论：
1、CEACAM6和MMP-9在胃癌组织中高表达,与胃癌的临床分期、浸润和转移有关。
2、CEACAM6和MMP-9可能共同参与了胃癌的发生和发展。
3、CEACAM6与MMP-9共同参与了胃癌组织微血管生成,且二者可能存在协同促进作用。
Objective:To investigate the role and significance in development and angiogenesis of gastric cancer by analyzing the association between angiogenesis and clinicopathological characteristics of gastric cancer and expression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM6) and matrix metalloproteinase 9 (MMP-9) in human gastric carcinoma tissue, adjacent normal tissues and incisal margin normal tissues.
Methods:Immunohistochemistry (Envision two-step) was used to detect the expression of CEACAM6 and MMP-9 in 54 cases of gastric cancer and adjacent normal tissues and 20 cases of incisal margin normal tissues. Microvessel density (MVD) was also detected by immunohistochemistry by Anti-factorⅧmarker.
Results:
1. The positive rate of CEACAM6 in gastric carcinoma tissue (85.19%) was significantly higher than those in adjacent normal tissue (40.74%) and incisal margin normal tissues (15%) (P< 0.05). The expression of CEACAM6 was associated significantly with depth of invasion and clinical stage of gastric cancer (P<0.05), but it was not associated with gender, age, histological type, tumor location, degree of differentiation and lymphnode metastasis (P>0.05).
2. The positive rate of MMP-9 in gastric carcinoma tissue (74.07%) was significantly higher than those in adjacent normal tissue (33.33%) and incisal margin normal tissues (10%) (P<0.05). The expression of MMP-9 was associated significantly with tumor location, degree of differentiation, lymphnode metastasis, depth of invasion and clinical stage of gastric cancer (P<0.05), but it was not associated with gender, age and histological type (P>0.05).
3. The value of MVD in gastric carcinoma tissue (32.17±8.97) was significantly higher than those in adjacent normal tissue (25.05±6.19) and incisal margin normal tissues (18.62±5.07) (P<0.05). The value of MVD was associated significantly with histological type, tumor location, degree of differentiation, lymphnode metastasis, depth of invasion and clinical stage of gastric cancer (P<0.05), but it was not associated with gender and age (P>0.05).
4. There was positive correlation between CEACAM6 and MMP-9 proteins expression in gastric carcinoma tissue (r=0.593, P=0.000).
5. The values of MVD in the group of positive expression of CEACAM6 and MMP-9 were higher than those in the group of negative expression of them respectively. The values of MVD in group of CEACAM6 and MMP-9 positive expression (33.16±9.38) were higher than in CEACAM6 and MMP-9 negative expression group (15.07±9.31) and CEACAM6 positive and MMP-9 negative expression group (22.95±3.99) (P<0.05).
Conclusions:
1. High expression of CEACAM6 and MMP-9 was associated with clinical stage, invasion and metastasis of gastric cancer.
2. CEACAM6 and MMP-9 jointly contributed to carcinogenesis and development of gastric cancer.
3. CEACAM6 and MMP-9 jointly contributed to tumor micro-angiogenesis of gastric cancer, and there may be synergistic effects of the both for angiogenesis of gastric cancer.
方法：用免疫组化法(Envision二步法)分别检测CEACAM6、MMP-9在54例胃癌组织、相应癌旁组织及20例手术切缘胃正常组织中的表达,并用Anti-factorⅧ标记血管,进行微血管计数。
结果：
1、CEACAM6在胃癌组织中的阳性表达率85.19%(46/54),明显高于相应癌旁组织40.74%(22/54)和手术切缘胃正常组织15%(3/20)(P<0.05),其表达与胃癌的浸润深度、临床分期明显相关(P<0.05),而与性别、年龄、组织类型、肿瘤部位、癌组织的分化程度和有无淋巴结转移无关(P>0.05)；
2、MMP-9在胃癌组织中的阳性表达率74.07%(40/54),较相应癌旁组织33.33%(18/54)及手术切缘胃正常组织10%(2/20)明显增高(P<0.05),其表达与肿瘤部位、癌组织的分化程度、有无淋巴结转移、浸润深度和临床分期相关(P<0.05),而与性别、年龄、组织类型无相关性(P>0.05)。
3、在胃癌组织中Anti-factorⅧ标记的微血管密度(MVD)值(32.17±8.97)明显高于相应癌旁组织(25.05±6.19)及手术切缘正常组织(18.62±5.07)(P<0.05),.其水平高低与肿瘤组织类型、肿瘤部位、癌组织的分化程度、有无淋巴结转移、浸润深度和临床分期相关(P<0.05),但与性别、年龄无关(P>0.05)。
4、CEACAM6与MMP-9在胃癌组织的表达呈正相关(r=0.593,P=0.000)。
5、CEACAM6阳性表达组和MMP-9阳性表达组的MVD值均高于其阴性表达组的MVD值(P<0.05)；且CEACAM6和MMP-9均为阳性表达的患者,其胃癌组织MVD值(33.16±9.38)高于CEACAM6和MMP-9均为阴性表达的患者(15.07±9.31),也高于CEACAM6阳性表达、MMP-9阴性表达的患者(22.95±3.99),差异均有统计学意义(P<0.05)。
结论：
1、CEACAM6和MMP-9在胃癌组织中高表达,与胃癌的临床分期、浸润和转移有关。
2、CEACAM6和MMP-9可能共同参与了胃癌的发生和发展。
3、CEACAM6与MMP-9共同参与了胃癌组织微血管生成,且二者可能存在协同促进作用。
Objective:To investigate the role and significance in development and angiogenesis of gastric cancer by analyzing the association between angiogenesis and clinicopathological characteristics of gastric cancer and expression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM6) and matrix metalloproteinase 9 (MMP-9) in human gastric carcinoma tissue, adjacent normal tissues and incisal margin normal tissues.
Methods:Immunohistochemistry (Envision two-step) was used to detect the expression of CEACAM6 and MMP-9 in 54 cases of gastric cancer and adjacent normal tissues and 20 cases of incisal margin normal tissues. Microvessel density (MVD) was also detected by immunohistochemistry by Anti-factorⅧmarker.
Results:
1. The positive rate of CEACAM6 in gastric carcinoma tissue (85.19%) was significantly higher than those in adjacent normal tissue (40.74%) and incisal margin normal tissues (15%) (P< 0.05). The expression of CEACAM6 was associated significantly with depth of invasion and clinical stage of gastric cancer (P<0.05), but it was not associated with gender, age, histological type, tumor location, degree of differentiation and lymphnode metastasis (P>0.05).
2. The positive rate of MMP-9 in gastric carcinoma tissue (74.07%) was significantly higher than those in adjacent normal tissue (33.33%) and incisal margin normal tissues (10%) (P<0.05). The expression of MMP-9 was associated significantly with tumor location, degree of differentiation, lymphnode metastasis, depth of invasion and clinical stage of gastric cancer (P<0.05), but it was not associated with gender, age and histological type (P>0.05).
3. The value of MVD in gastric carcinoma tissue (32.17±8.97) was significantly higher than those in adjacent normal tissue (25.05±6.19) and incisal margin normal tissues (18.62±5.07) (P<0.05). The value of MVD was associated significantly with histological type, tumor location, degree of differentiation, lymphnode metastasis, depth of invasion and clinical stage of gastric cancer (P<0.05), but it was not associated with gender and age (P>0.05).
4. There was positive correlation between CEACAM6 and MMP-9 proteins expression in gastric carcinoma tissue (r=0.593, P=0.000).
5. The values of MVD in the group of positive expression of CEACAM6 and MMP-9 were higher than those in the group of negative expression of them respectively. The values of MVD in group of CEACAM6 and MMP-9 positive expression (33.16±9.38) were higher than in CEACAM6 and MMP-9 negative expression group (15.07±9.31) and CEACAM6 positive and MMP-9 negative expression group (22.95±3.99) (P<0.05).
Conclusions:
1. High expression of CEACAM6 and MMP-9 was associated with clinical stage, invasion and metastasis of gastric cancer.
2. CEACAM6 and MMP-9 jointly contributed to carcinogenesis and development of gastric cancer.
3. CEACAM6 and MMP-9 jointly contributed to tumor micro-angiogenesis of gastric cancer, and there may be synergistic effects of the both for angiogenesis of gastric cancer.
引文
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[1]侯志波,郑杰癌胚抗原基因家族与肿瘤.《生命的化学》,2005,25(1)：37-39.
[2]Bamberger AM,Riethdorf L,Nollau P,et al.Dysregulated expression or CD66a(BGP, C-CAM),an adhesion molecule of the CEA family, in endometrial cancer [J]. Am J Pathol,1998,152:1401-1406.
[3]BB Singer,I Schcffran, B Obrink,et al.The tumor growth-inhibiting cell adhesion molecule CEACAM 1 (C-CAM) is differently expressed in proliferating and quiescent epithelial cells and regulates cell prolifcration[J].Cancer Res,2000,60:1236-1244.
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