子宫内膜腺癌中Metastin及MMP-9的表达及临床意义
摘要
子宫内膜癌(Endometrium Carcinoma)为女性生殖系统三大恶性肿瘤之一,其中子宫内膜腺癌占80%以上,严重威胁女性生殖健康及生命。近年来,发病率呈上升趋势且趋于年轻化。目前随着分子遗传学与分子生物学、免疫学技术相结合,呈现出越来越多关于子宫内膜腺癌在分子水平致癌及促癌机制的研究。KiSS-1基因是新近发现的一个崭新的肿瘤转移抑制基因,其表达产物Metastin特异性低表达于肿瘤组织中的特点使之成为近年的研究热点。MMPs是一组锌离子依赖性蛋白水解酶超家族,MMP-9是该家族中重要的一员,高表达于多种人类恶性肿瘤组织中,具有促进恶性肿瘤发生、发展的作用。这两种蛋白在肿瘤组织中的表达呈负相关,二者相互调控、相互制约共同参与了恶性肿瘤的发生、发展。
本研究采用免疫组织化学方法检测Metastin和MMP-9在子宫内膜腺癌组织、不典型增生子宫内膜组织及正常子宫内膜组织中的表达情况。研究结果显示:Metastin在子宫内膜腺癌中的阳性表达率明显低于其在非癌性子宫内膜组织中的表达率,且与子宫内膜腺癌的组织学分级、肌层浸润深度及手术-病理分期等临床病理参数呈负相关。从正常子宫内膜组织、不典型增生子宫内膜组织和子宫内膜腺癌组织中MMP-9的表达逐渐增强,与手术-病理分期显著正相关,而与组织学分级、肌层浸润深度及有无淋巴结转移无关。
子宫内膜腺癌与其它恶性肿瘤一样都是多种因素引起的,Metastin和MMP-9参与了子宫内膜腺癌的发生及恶性进展的过程,二者在子宫内膜腺癌中具有相反的生物效应,存在负相关。在子宫内膜腺癌组织中联合检测二者将有望为临床早期诊断、治疗、判断恶性程度及评估预后等一系列问题提供理论依据。
Objective:
This article aims to research the expression of Metastin and MMP-9 in endometrial adenocarcinoma, atypical hyperplasia endometrium and normal endometrium,and explore the role it plays in the occurrence and development of endometrial adenocarcinoma, and to provide theoretical basis for diagnosis judgment of malignancy degree, and prognosis in endometrial adenocarcinoma, and to provide new theoretical basis for gene therapy of endometrial adenocarcinoma.
Methods:
35 specimens of endometrial adenocarcinoma which are collected randomly are used as experimental group, and 20 atypical hyperplasia endometrium specimens of patients and 22 normal endometrium specimens are used as the control group. For the purpose of testing the expression of Metastin and MMP-9 in normal endometrium, atypical hyperplasia endometrium and endometrial adenocarcinoma, and of analyzing the relationship between the expression of Metastin and MMP-9 and various clinic-pathology parameters, and of analyzing the relationship between Metastin and MMP-9, immunohistochemistry is adopted.In order to make statistical analysis, SPSS170.0 statistical software package is used.
Results: Comparing between the three groups, the difference is significant(P<0.05).
1. The positive expression rates of Metastin in normal endometrium, atypical hyperplasia endometrium and endometrial carcinoma respectively are 86.4%, 90% and 37.1%.Comparing between the three groups, the difference is significant(P<0.05).There is no significant difference between the positive expression rates of Metastin in endometrial carcinoma and atypical hyperplasia endometrium (χ2=0, P>0.05). The positive expression of Metastin in normal endometrium and atypical hyperplasia endometrium is significantly different from that in endometrial carcinoma (P<0.05).
2. The positive expression rates of MMP-9 in normal endometrium, atypical hyperplasia endometrium and endometrial adenocarcinoma are 13.6%, 30% and 62.9%. Comparing between the three groups, the difference is significant(P<0.05).The positive expression rates of MMP-9 in endometrial carcinoma is no significant difference from atypical hyperplasia endometrium(χ2=0.836,P>0.05). They respectively compare with endometrial adenocarcinoma, the difference is very significant, P<0.05.
3. The positive expression rate of Metastin in the Well-differentiated endometrial adenocarcinoma is 56.3%,the same time, the positive expression rate of Metastin in the group of moderately and poorly differentiated is 21.1%,compare among the two groups, there is significant difference (P<0.05).In the Well-differentiated endometrial adenocarcinoma, moderately and poorly differentiated endometrial adenocarcinoma, the positive expression rates of MMP-9 are 50% and 73.7%, there is no significant difference (P>0.05).
4. The positive expression rate of Metastin in the muscular layer infiltration depth<1/2 of endometrial adenocarcinoma groups is 83.3%, and in the muscular layer infiltration depth≥1/2 groups is 22.2%, by statistical comparison, the difference is significant (P<0.05). The positive expression rate of MMP-9 in the two groups are separately 30.8% and 66.7%,the statistical difference is not significant (P>0.05)
5. None is positive expression of Metastin in the with lymph node metastasis group, whereas the positive expression rate of Metastin in without lymph node metastasis group is 46.4%, comparing between them the difference is significant (P<0.05).The positive expression rate of MMP-9 in with and without lymph node metastasis of endometrial adenocarcinoma are 85.7% and 57.1%, compared between them there is no significant difference (P>0.05).
6. In the surgical-pathological staging I group, II and III group of endometrial adenocarcinoma, the positive expression rate of Metastin respectively are 54.5% and 7.7%, there is significant difference between them (P<0.05). In surgical-pathological staging I group, II and III group of endometrial adenocarcinoma, the positive expression rates of MMP-9 respectively are 45.5% and 92.2%, there is significant statistics difference between them (P<0.05).
7. The positive expression rate of Metastin and MMP-9 shows negative relationship(γ=-0.388,P<0.05).
Conclusion:
1.Lower expression of Metastin may promote malignant progress of endometrial adenocarcinoma.
2. Higher expression of MMP-9 may contribute to occurrence and development in endometrial adenocarcinoma.
3. Lower expression of Metastin in endometrial adenocarcinoma may indicate more malignant and easier to relapse.
4. Higher expression of MMP-9 in endometrial adenocarcinoma may indicate more aggressive and poor prognosis.
5. In endometrial adenocarcinoma tissues,the positive expression of Metastin and MMP-9 shows negative correlation. They are antagonistic effect on occurrence and development of endometrial adenocarcinoma.
6. Monitoring the expression of Metastin and MMP-9 in endometrial adenocarcinoma can be used to determine the malignant tumor degree and prognosis.
本研究采用免疫组织化学方法检测Metastin和MMP-9在子宫内膜腺癌组织、不典型增生子宫内膜组织及正常子宫内膜组织中的表达情况。研究结果显示:Metastin在子宫内膜腺癌中的阳性表达率明显低于其在非癌性子宫内膜组织中的表达率,且与子宫内膜腺癌的组织学分级、肌层浸润深度及手术-病理分期等临床病理参数呈负相关。从正常子宫内膜组织、不典型增生子宫内膜组织和子宫内膜腺癌组织中MMP-9的表达逐渐增强,与手术-病理分期显著正相关,而与组织学分级、肌层浸润深度及有无淋巴结转移无关。
子宫内膜腺癌与其它恶性肿瘤一样都是多种因素引起的,Metastin和MMP-9参与了子宫内膜腺癌的发生及恶性进展的过程,二者在子宫内膜腺癌中具有相反的生物效应,存在负相关。在子宫内膜腺癌组织中联合检测二者将有望为临床早期诊断、治疗、判断恶性程度及评估预后等一系列问题提供理论依据。
Objective:
This article aims to research the expression of Metastin and MMP-9 in endometrial adenocarcinoma, atypical hyperplasia endometrium and normal endometrium,and explore the role it plays in the occurrence and development of endometrial adenocarcinoma, and to provide theoretical basis for diagnosis judgment of malignancy degree, and prognosis in endometrial adenocarcinoma, and to provide new theoretical basis for gene therapy of endometrial adenocarcinoma.
Methods:
35 specimens of endometrial adenocarcinoma which are collected randomly are used as experimental group, and 20 atypical hyperplasia endometrium specimens of patients and 22 normal endometrium specimens are used as the control group. For the purpose of testing the expression of Metastin and MMP-9 in normal endometrium, atypical hyperplasia endometrium and endometrial adenocarcinoma, and of analyzing the relationship between the expression of Metastin and MMP-9 and various clinic-pathology parameters, and of analyzing the relationship between Metastin and MMP-9, immunohistochemistry is adopted.In order to make statistical analysis, SPSS170.0 statistical software package is used.
Results: Comparing between the three groups, the difference is significant(P<0.05).
1. The positive expression rates of Metastin in normal endometrium, atypical hyperplasia endometrium and endometrial carcinoma respectively are 86.4%, 90% and 37.1%.Comparing between the three groups, the difference is significant(P<0.05).There is no significant difference between the positive expression rates of Metastin in endometrial carcinoma and atypical hyperplasia endometrium (χ2=0, P>0.05). The positive expression of Metastin in normal endometrium and atypical hyperplasia endometrium is significantly different from that in endometrial carcinoma (P<0.05).
2. The positive expression rates of MMP-9 in normal endometrium, atypical hyperplasia endometrium and endometrial adenocarcinoma are 13.6%, 30% and 62.9%. Comparing between the three groups, the difference is significant(P<0.05).The positive expression rates of MMP-9 in endometrial carcinoma is no significant difference from atypical hyperplasia endometrium(χ2=0.836,P>0.05). They respectively compare with endometrial adenocarcinoma, the difference is very significant, P<0.05.
3. The positive expression rate of Metastin in the Well-differentiated endometrial adenocarcinoma is 56.3%,the same time, the positive expression rate of Metastin in the group of moderately and poorly differentiated is 21.1%,compare among the two groups, there is significant difference (P<0.05).In the Well-differentiated endometrial adenocarcinoma, moderately and poorly differentiated endometrial adenocarcinoma, the positive expression rates of MMP-9 are 50% and 73.7%, there is no significant difference (P>0.05).
4. The positive expression rate of Metastin in the muscular layer infiltration depth<1/2 of endometrial adenocarcinoma groups is 83.3%, and in the muscular layer infiltration depth≥1/2 groups is 22.2%, by statistical comparison, the difference is significant (P<0.05). The positive expression rate of MMP-9 in the two groups are separately 30.8% and 66.7%,the statistical difference is not significant (P>0.05)
5. None is positive expression of Metastin in the with lymph node metastasis group, whereas the positive expression rate of Metastin in without lymph node metastasis group is 46.4%, comparing between them the difference is significant (P<0.05).The positive expression rate of MMP-9 in with and without lymph node metastasis of endometrial adenocarcinoma are 85.7% and 57.1%, compared between them there is no significant difference (P>0.05).
6. In the surgical-pathological staging I group, II and III group of endometrial adenocarcinoma, the positive expression rate of Metastin respectively are 54.5% and 7.7%, there is significant difference between them (P<0.05). In surgical-pathological staging I group, II and III group of endometrial adenocarcinoma, the positive expression rates of MMP-9 respectively are 45.5% and 92.2%, there is significant statistics difference between them (P<0.05).
7. The positive expression rate of Metastin and MMP-9 shows negative relationship(γ=-0.388,P<0.05).
Conclusion:
1.Lower expression of Metastin may promote malignant progress of endometrial adenocarcinoma.
2. Higher expression of MMP-9 may contribute to occurrence and development in endometrial adenocarcinoma.
3. Lower expression of Metastin in endometrial adenocarcinoma may indicate more malignant and easier to relapse.
4. Higher expression of MMP-9 in endometrial adenocarcinoma may indicate more aggressive and poor prognosis.
5. In endometrial adenocarcinoma tissues,the positive expression of Metastin and MMP-9 shows negative correlation. They are antagonistic effect on occurrence and development of endometrial adenocarcinoma.
6. Monitoring the expression of Metastin and MMP-9 in endometrial adenocarcinoma can be used to determine the malignant tumor degree and prognosis.
引文
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