KLK10在子宫内膜腺癌组织中表达及其与ER、PR表达的相关性研究
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摘要
KLK10在子宫内膜腺癌中的表达及其与ER、PR表达的相关性研究
目的:
检测人组织激肽释放酶10(Kallikrein10, KLK10)在正常子宫内膜组织、子宫内膜增生症组织及子宫内膜腺癌组织中的表达,分析其与子宫内膜癌临床病理特征之间的关系,同时对其与雌激素受体(Estrogen receptor, ER)和孕激素受体(Progesterone receptor, PR)之间的相关性进行研究,以探讨KLK10在子宫内膜腺癌发生发展中的作用及其与ER和PR的相互关系,为子宫内膜癌的诊断、治疗提供新的依据。
方法:
以19例子宫内膜增生症组织、34例子宫内膜腺癌组织为研究对象,以12例正常子宫内膜组织做为对照,应用免疫组织化学方法测定KLK10在不同组织中的表达,比较KLK10在不同组织中表达的差异,分析KLK10的表达与子宫内膜癌手术病理分期、组织学分级、年龄等临床病理学参数的关系;同时检测34例子宫内膜腺癌组织中ER、PR的表达,并分析KLK10、ER和PR之间表达的相关性,初步探讨KLK10、ER和PR与子宫内膜腺癌发生发展的关系。KLK10在不同组织中的表达及其与各临床病理指标之间关系的比较采用方差检验,KLK10、ER、PR在子宫内膜癌组织中表达之间的相关性分析Fisher确切概率法及Pearson相关分析。
结果:
1.免疫组织化学结果显示,KLK10表达阳性染色主要定位于腺体上皮细胞质中,KLK10在正常子宫内膜组织、子宫内膜增生症组织、子宫内膜癌组织中表达的阳性率分别为91.7%(11/12)、78.9%(15/18)、38.2%(13/34),灰度值平均值分别为:125.25±21.47、135.08±30.67、151.09±21.54。KLK10在子宫内膜癌组织中的表达显著低于正常子宫内膜组织及子宫内膜增生症组织,两两比较,差异有显著性(P<0.05)。KLK10在手术病理分期为Ⅰ期、Ⅱ期、Ⅲ期的内膜腺癌组织中表达阳性率为31.8%(7/22)、50.0%(3/6)、50.0%(3/6),灰度值平均值分别为:148.47±30.51、143.63±35.77、168.16±23.94,两两比较,差异无显著性(P>0.05)。KLK10在G1、G2、G3级的内膜腺癌组织中表达阳性率分别为36.3%(4/11)、41.2%(7/17)、33.3%(2/6),灰度值平均值分别为:151.43±29.45、150.97±33.51、150.80±29.67,两两比较,差异无显著性(P>0.05)。KLK10在年龄≤50岁、>50岁的子宫内膜腺癌组织中的阳性率分别为33.3%(5/15)、41.2%(8/19),灰度值平均值为:161.45±29.19、142.91±30.03,两者比较差异无明显显著性(P>0.05)。KLK10表达下调或缺失与子宫内膜腺癌的手术病理分期、组织学分级及患者年龄无关。2. 34例子宫内膜腺癌组织中有23例呈ER阳性表达,表达阳性率为67.6%,19例呈PR阳性表达,阳性率为55.9%,ER阳性组KLK10蛋白表达阳性率为69.6%(16/23),ER阴性组KLK10蛋白表达阳性率为45.5%(5/11),PR阳性组KLK10蛋白表达阳性率为78.9%(15/19),PR阴性组KLK10蛋白表达阳性率为33.3%(5/15),Fisher确切概率法及Pearson相关分析显示,子宫内膜癌组织中KLK10蛋白表达与ER蛋白表达呈正相关(P<0.01),KLK10蛋白表达与PR蛋白表达呈正相关(P<0.01)。
结论:
1. KLK10蛋白在子宫内膜腺癌组织中的表达水平明显低于正常子宫内膜组织及子宫内膜增生症组织;子宫内膜腺癌组织中,KLK10蛋白的表达与组织学分级、手术病理分期及患者的年龄无关;提示KLK10蛋白表达缺失或表达下调可能在子宫内膜癌的发生过程中起重要作用。
2. KLK10蛋白在子宫内膜腺癌组织中表达降低,ER、PR在子宫内膜腺癌组织中表达也降低,KLK10蛋白在子宫内膜腺癌组织中的表达和ER、PR在子宫内膜腺癌组织中的表达有一定的相关性,推测KLK10基因可能参与ER、PR表达的调控。KLK10蛋白单独或与ER、PR三者共同作用,影响子宫内膜的生长及凋亡。
The expression of KLK10 in endometrioid adenocarcinoma and its correlation with ER, PR
Obective:
This study was designed to evaluate the expression of KLK10 in normal endometria , endometrial hyperplasia, endometrioid adenocarcinoma and to investigate the relationships between their expressions and the clinicopathological parameters and prognosis respectively, and we also analysed the correlation of KLK10 expressions with ER, PR in endometrioid adenocarcinoma, which may reveal the role of KLK10 in the pathogenesis and progression of endometrioid adenocarcinoma and the correlation with ER, PR. Thus we would find promising targets for diagnosis and therapy.
Method:
The research objects were 19 endometrial hyperplasia tissues and 34 endometrioid adenocarcinoma tissues, the control group was 12 normal endometrial. Immuno- histochemical methods were used to detect the protein expression of KLK10 in different tissues. To compare the difference of the expression in different tissues and to analyse the expression of KLK10 in endometrioid adenocarcinoma and the relationship with clinical parameters, such as surgical pathology staging, histopa-thological grading, and age. We also detected ER, PR expression in 34 cases of endometrial adenocarcinoma and analyzed the correlation between them. Preliminary discussed the relations of KLK10, ER and PR in endometrial adenocarcinoma occurrence and development. The correlation of the expression of KLK10 in endometrial adenocarcinoma, normal endometrial tissue and endometrial hyperplasia, the correlation of the factors with the clinical features and the correlations of KLK10, ER and PR expression levels in adenocarcinoma endometrium were evaluated by chi-square test, fisher probability method and the Pearson correlation analysis.
Results:
1. KLK10 protein immunoreactivity was observed in the cytoplasm. Positive KLK10 protein immunostaining were observed in 13 of 34(38.2%) endometrial carcinoma samples, 11 of 12(91.7%) normal endometria, 15 of 18(78.9%) endometrial hyperplasia, average gray values were 151.09±21.54, 125.25±21.47, 135.08±30.67, average gray values were 151.09±21.54,125.25±21.47,135.08±30.67. The expression of KLK10 in endometrial carcinoma was significantly less than that in normal endometrial hyperplasia (P<0.05). The positive expression rate in Surgical pathology stageⅠ,ⅡandⅢwere 50.0%(3/6), 50.0%(3/6), 31.8%(7/22),average gray values were 148.47±30.51, 143.63±35.77, 168.16±23.94, the positive expression rate in histological grade 1, 2 and 3 were 36.3%(4/11), 41.2%(7/17), 33.3%(2/6), average gray values were 151.43±29.45, 150.97±33.51, 150.80±29.67, the positive expression rate in be equal or greater than 50 and over 50 were 33.3%(5/15), 41.2%(8/19), average gray values were 161.45±29.19 ,142.91±30.03. There were no significant association between KLK10 expression and Surgical pathology stage, histological grade and age.
2. Positive ER immunostaining were observed in 23 of 34(67.6%) endometrial carcinoma samples. Positive PR immunostaining were observed in 19 of 34(55.9%) endometrial carcinoma samples. The positive rates of KLK10 expression were 45.5% (5/11) in ER-negative carcinomas, 69.6% (16/23) in ER-positive carcinomas. The positive rates of KLK10 expression were 33.3% (5/15) in PR-negative carcinomas, 78.9% (15/19) in PR-positive carcinomas. The expression of KLK10 was positively correlated with ER expression (P<0.01) and PR expression (P<0.01).
Conclusion:
1. The positive expression rate of KLK10 in endometrioid adenocarcinoma was significantly higher than normal endometrial and endometrial hyperplasia tissue; the expression of KLK10 had no relation with the age, histological classification and clincal stage. This suggested that absence or downregulated expression of KLK10 possibly played an improtant role in the genesis and development of endometrioid adenocarcinoma.
2. The expression of KLK10 in endometrioid adenocarcinoma was lessen, The expression of ER, PR in endometrioid adenocarcinoma was lessen. KLK10 protein in endometrial adenocarcinoma tissues and ER, PR in endometrial adenocarcinoma tissues have a certain correlation. We speculated that KLK10 gene might be involved in ER, PR expression regulation. KLK10 protein alone or with ER, PR interaction among affect endometrial growth and apoptosis.
目的:
检测人组织激肽释放酶10(Kallikrein10, KLK10)在正常子宫内膜组织、子宫内膜增生症组织及子宫内膜腺癌组织中的表达,分析其与子宫内膜癌临床病理特征之间的关系,同时对其与雌激素受体(Estrogen receptor, ER)和孕激素受体(Progesterone receptor, PR)之间的相关性进行研究,以探讨KLK10在子宫内膜腺癌发生发展中的作用及其与ER和PR的相互关系,为子宫内膜癌的诊断、治疗提供新的依据。
方法:
以19例子宫内膜增生症组织、34例子宫内膜腺癌组织为研究对象,以12例正常子宫内膜组织做为对照,应用免疫组织化学方法测定KLK10在不同组织中的表达,比较KLK10在不同组织中表达的差异,分析KLK10的表达与子宫内膜癌手术病理分期、组织学分级、年龄等临床病理学参数的关系;同时检测34例子宫内膜腺癌组织中ER、PR的表达,并分析KLK10、ER和PR之间表达的相关性,初步探讨KLK10、ER和PR与子宫内膜腺癌发生发展的关系。KLK10在不同组织中的表达及其与各临床病理指标之间关系的比较采用方差检验,KLK10、ER、PR在子宫内膜癌组织中表达之间的相关性分析Fisher确切概率法及Pearson相关分析。
结果:
1.免疫组织化学结果显示,KLK10表达阳性染色主要定位于腺体上皮细胞质中,KLK10在正常子宫内膜组织、子宫内膜增生症组织、子宫内膜癌组织中表达的阳性率分别为91.7%(11/12)、78.9%(15/18)、38.2%(13/34),灰度值平均值分别为:125.25±21.47、135.08±30.67、151.09±21.54。KLK10在子宫内膜癌组织中的表达显著低于正常子宫内膜组织及子宫内膜增生症组织,两两比较,差异有显著性(P<0.05)。KLK10在手术病理分期为Ⅰ期、Ⅱ期、Ⅲ期的内膜腺癌组织中表达阳性率为31.8%(7/22)、50.0%(3/6)、50.0%(3/6),灰度值平均值分别为:148.47±30.51、143.63±35.77、168.16±23.94,两两比较,差异无显著性(P>0.05)。KLK10在G1、G2、G3级的内膜腺癌组织中表达阳性率分别为36.3%(4/11)、41.2%(7/17)、33.3%(2/6),灰度值平均值分别为:151.43±29.45、150.97±33.51、150.80±29.67,两两比较,差异无显著性(P>0.05)。KLK10在年龄≤50岁、>50岁的子宫内膜腺癌组织中的阳性率分别为33.3%(5/15)、41.2%(8/19),灰度值平均值为:161.45±29.19、142.91±30.03,两者比较差异无明显显著性(P>0.05)。KLK10表达下调或缺失与子宫内膜腺癌的手术病理分期、组织学分级及患者年龄无关。2. 34例子宫内膜腺癌组织中有23例呈ER阳性表达,表达阳性率为67.6%,19例呈PR阳性表达,阳性率为55.9%,ER阳性组KLK10蛋白表达阳性率为69.6%(16/23),ER阴性组KLK10蛋白表达阳性率为45.5%(5/11),PR阳性组KLK10蛋白表达阳性率为78.9%(15/19),PR阴性组KLK10蛋白表达阳性率为33.3%(5/15),Fisher确切概率法及Pearson相关分析显示,子宫内膜癌组织中KLK10蛋白表达与ER蛋白表达呈正相关(P<0.01),KLK10蛋白表达与PR蛋白表达呈正相关(P<0.01)。
结论:
1. KLK10蛋白在子宫内膜腺癌组织中的表达水平明显低于正常子宫内膜组织及子宫内膜增生症组织;子宫内膜腺癌组织中,KLK10蛋白的表达与组织学分级、手术病理分期及患者的年龄无关;提示KLK10蛋白表达缺失或表达下调可能在子宫内膜癌的发生过程中起重要作用。
2. KLK10蛋白在子宫内膜腺癌组织中表达降低,ER、PR在子宫内膜腺癌组织中表达也降低,KLK10蛋白在子宫内膜腺癌组织中的表达和ER、PR在子宫内膜腺癌组织中的表达有一定的相关性,推测KLK10基因可能参与ER、PR表达的调控。KLK10蛋白单独或与ER、PR三者共同作用,影响子宫内膜的生长及凋亡。
The expression of KLK10 in endometrioid adenocarcinoma and its correlation with ER, PR
Obective:
This study was designed to evaluate the expression of KLK10 in normal endometria , endometrial hyperplasia, endometrioid adenocarcinoma and to investigate the relationships between their expressions and the clinicopathological parameters and prognosis respectively, and we also analysed the correlation of KLK10 expressions with ER, PR in endometrioid adenocarcinoma, which may reveal the role of KLK10 in the pathogenesis and progression of endometrioid adenocarcinoma and the correlation with ER, PR. Thus we would find promising targets for diagnosis and therapy.
Method:
The research objects were 19 endometrial hyperplasia tissues and 34 endometrioid adenocarcinoma tissues, the control group was 12 normal endometrial. Immuno- histochemical methods were used to detect the protein expression of KLK10 in different tissues. To compare the difference of the expression in different tissues and to analyse the expression of KLK10 in endometrioid adenocarcinoma and the relationship with clinical parameters, such as surgical pathology staging, histopa-thological grading, and age. We also detected ER, PR expression in 34 cases of endometrial adenocarcinoma and analyzed the correlation between them. Preliminary discussed the relations of KLK10, ER and PR in endometrial adenocarcinoma occurrence and development. The correlation of the expression of KLK10 in endometrial adenocarcinoma, normal endometrial tissue and endometrial hyperplasia, the correlation of the factors with the clinical features and the correlations of KLK10, ER and PR expression levels in adenocarcinoma endometrium were evaluated by chi-square test, fisher probability method and the Pearson correlation analysis.
Results:
1. KLK10 protein immunoreactivity was observed in the cytoplasm. Positive KLK10 protein immunostaining were observed in 13 of 34(38.2%) endometrial carcinoma samples, 11 of 12(91.7%) normal endometria, 15 of 18(78.9%) endometrial hyperplasia, average gray values were 151.09±21.54, 125.25±21.47, 135.08±30.67, average gray values were 151.09±21.54,125.25±21.47,135.08±30.67. The expression of KLK10 in endometrial carcinoma was significantly less than that in normal endometrial hyperplasia (P<0.05). The positive expression rate in Surgical pathology stageⅠ,ⅡandⅢwere 50.0%(3/6), 50.0%(3/6), 31.8%(7/22),average gray values were 148.47±30.51, 143.63±35.77, 168.16±23.94, the positive expression rate in histological grade 1, 2 and 3 were 36.3%(4/11), 41.2%(7/17), 33.3%(2/6), average gray values were 151.43±29.45, 150.97±33.51, 150.80±29.67, the positive expression rate in be equal or greater than 50 and over 50 were 33.3%(5/15), 41.2%(8/19), average gray values were 161.45±29.19 ,142.91±30.03. There were no significant association between KLK10 expression and Surgical pathology stage, histological grade and age.
2. Positive ER immunostaining were observed in 23 of 34(67.6%) endometrial carcinoma samples. Positive PR immunostaining were observed in 19 of 34(55.9%) endometrial carcinoma samples. The positive rates of KLK10 expression were 45.5% (5/11) in ER-negative carcinomas, 69.6% (16/23) in ER-positive carcinomas. The positive rates of KLK10 expression were 33.3% (5/15) in PR-negative carcinomas, 78.9% (15/19) in PR-positive carcinomas. The expression of KLK10 was positively correlated with ER expression (P<0.01) and PR expression (P<0.01).
Conclusion:
1. The positive expression rate of KLK10 in endometrioid adenocarcinoma was significantly higher than normal endometrial and endometrial hyperplasia tissue; the expression of KLK10 had no relation with the age, histological classification and clincal stage. This suggested that absence or downregulated expression of KLK10 possibly played an improtant role in the genesis and development of endometrioid adenocarcinoma.
2. The expression of KLK10 in endometrioid adenocarcinoma was lessen, The expression of ER, PR in endometrioid adenocarcinoma was lessen. KLK10 protein in endometrial adenocarcinoma tissues and ER, PR in endometrial adenocarcinoma tissues have a certain correlation. We speculated that KLK10 gene might be involved in ER, PR expression regulation. KLK10 protein alone or with ER, PR interaction among affect endometrial growth and apoptosis.
引文
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[42]连丽娟,林巧稚.妇科肿瘤学[M].北京:人民卫生出版社,1994,452-475.
[43] Tryggvason K,Hoyhtya M,Salo T.Proteolytic degradation of extracellualar matrix in tumor invasion. Biochem Byophys Acta, 1987,907:191-207.
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[51] Runocz CD, Nuchtem LM, Braunstein JD, Jones JG. Heterogeneity receptor Status in primary and metastatic endometrial cancer.[J]Gynecology Oncology1990, 38:437-441.
[52] Wang D, Konishi I,Koshiya M, Mandai M, Nanbu Y IshikY Mori T, Fujii S . Expression of cerb-2 protein and demlal groh receptor in endometrialcarcinomas Correlation with clinicopathologic and sex steroid receptor status. [J).Cancer 1993,72: 2628-2637.
[53] Yamauchi N,Sakamoto A,Uozald H, Iihara K, Mechanism immunohistochemical and analysis of endometrial adenocarcinoma for bcl-2 and p53 in relation to expression of sex Pathology. Steroid rector and proliferative activity.[J].Int Gynecology1 996,15:202-208.
[54] Balmer NN, Richer JK, Spoelstra NS, Torkko KC, Lyle PL, Singh M. Steroid receptor coactivator AIB 1 in endometrial carcinoma, hyperplasia and normal endometrium: Correlation with clinicopathologic parameters and biomarkers. Mod Pathol. 2006 Dec, 19(12):1593-605.
[55] He B,Feng Q,Mukherjee A,Lonard DM,DeMayo FJ, Katzenellenbogen BS, Lydon JP, 0'Malley BW. A repressive role for prohibitin in estrogen signaling.Mol Endocrinol.2008 Feb, 22(2):344-60.
[56] Taylor AH, Azzawi F, Pringle JH, et al·Inhibition of endometrlalcarcinoma cell growth using antisense estrogen receptoroligo deoxyribonucleotides[J]. Anticancer Research 2002, 22: 3993-4003.