乙酰肝素酶和尿激酶型纤溶酶原激活物在子宫内膜癌中的表达和临床意义
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摘要
目的:检测乙酰肝素酶(heparanase Hpa)、尿激酶型纤溶酶原激活物(urokinase-type plasminogen activator uPA)在正常子宫内膜、增生过长子宫内膜、不典型增生子宫内膜及子宫内膜腺癌中的表达及相关性。探讨Hpa、uPA表达与子宫内膜癌临床病理特征的关系。
     方法:采用多克隆抗体及免疫组织化学S-P法,检测16例正常子宫内膜、18例增生过长子宫内膜、20例不典型增生子宫内膜及46例子宫内膜腺癌中Hpa、uPA的表达。同时分析二者表达与子宫内膜癌临床病理分期、癌灶肌层浸润深度、淋巴结转移和组织病理学分级的相关性。
     结果:
     1、Hpa在子宫内膜癌中阳性表达率为54%,明显高于正常子宫内膜、增生过长内膜以及不典型增生子宫内膜中的表达,差异有显著性(P<0.005)。Hpa在子宫内膜癌中的阳性表达率随临床分期的增加而增加,Ⅲ期患者内膜癌组织中Hpa阳性率(89%)明显高于Ⅰ期(33%)、Ⅱ期(69%)患者,有显著性差异(P=0.008)。Hpa在肌层浸润>1/2中阳性表达率为77%,明显高于无肌层浸润(25%)或浸润≤1/2组(38%)(P<0.05)。Hpa与子宫内膜癌临床病理分期、肌层浸润深度、淋巴结转移密切相关(P<0.05),与病理分级无明显相关性(P>0.05)。
     2.uPA在正常子宫内膜、增生过长子宫内膜以及不典型增生子宫内膜和子宫内膜癌中的阳性表达率分别为13%、11%、25%和57%,uPA在子宫内膜癌组织中的表达明显高于正常内膜,差异有统计学意义(P<0.005)。uPA在内膜癌Ⅲ期患者的阳性表达率(89%)明显高于Ⅰ期(38%)、Ⅱ期(69%)患者,有显著性差异(P=0.016)。uPA在肌层浸润>1/2中阳性表达率为77%,明显高于无肌层浸润(38%)或浸润≤1/2组(38%)(P<0.05)。uPA与子宫内膜癌临床病理分期、肌层浸润深度、淋巴结转移密切相关(P<0.05),亦与病理分级无明显相关性(P>0.05)。
     3、Hpa与uPA相关性分析显示,二者的表达无明显相关性(p>0.05)。
     结论:
     1.Hpa和uPA在子宫内膜腺癌组织中的表达明显高于正常子宫内膜、增生过长子宫内膜以及不典型增生子宫内膜组织,可能与子宫内膜癌的发生有关。
     2.Hpa和uPA在子宫内膜腺癌组织中的表达均与临床病理分期、肌层浸润深度和淋巴结转移密切相关,与病理分级无明显相关性,提示Hpa和uPA可能在癌的侵袭、转移中起作用,并提示二者可作为反映子宫内膜癌生物学行为的参考指标。
     3.Hpa和uPA在子宫内膜腺癌组织中的表达均升高,但无明显相关性,二者在内膜癌中有无相互作用还有待于进一步的研究。
Objectives: To detect the expression of Hpa (heparananse) and uPA (urokinase-type plasminogen activator) in the normal endometrium, over-hyperplasia endometrium, atypical hyperplasia endometrium and endometrial adenocarcinoma. To explore the relation between the expression of Hpa and uPA in the clinical pathological characteristics of endometrial carcinoma.
     Methods: The multiple clonal antibodies and the S-P immunohistochemical method were adopted to detect the expression of Hpa and uPA in 16 cases of the normal endometrium, 18 cases of the over-hyperplasia endometrium, 20 cases of atypical hyperplasia endometrium and 46 cases of endometrial adenocarcinoma. At the same time, the correlation between the expression of Hpa and uPA and the clinical pathological staging of endometrial carcinoma, the degree of depth of infiltration at muscular lever of carcinoma focus, the metastasis of lymph nodes and the pathological grading of tissues was analyzed.
     Results:
     1.The positive expression rate of Hpa in the endometrial carcinoma was 54%, which was obviously higher than that in the normal endometrium, over-hyperplasia endometrium and atypical hyperplasia endometrium, presenting a marked difference (P<0.005). The positive expression rate of Hpa in endometrial carcinoma increased with the increase of clinical staging. The positive rate of Hpa in stage-Ⅲendometrial carcinoma patients(89%) was obviously higher than stage-Ⅰ(33%) and stage-Ⅱ(69%) patients and the difference was notable (P=0.008). The positive expression rate of Hpa in the patients that muscular infiltration depth were over 1/2 was 77%, which was obviously higher than that at non-muscular infiltration (25%) or muscular infiltration depth was less than or equal to 1/2 (38%) (P<0.05). Hpa was closely related to the clinical pathological staging of endometrial carcinoma, the degree of depth of infiltration at muscular lever and the metastasis of lymph nodes (P<0.05) and not show close relation with the pathological grading (P>0.05).
     2. The positive expression rate of uPA in the normal endometrium, over-hyperplasia endometrium and atypical hyperplasia endometrium and endometrial carcinoma was 13%, 11%, 25% and 57% respectively. The expression of uPA in the tissue of endometrial carcinoma was obviously higher than that in normal endomembrane and the difference bore significance in statistics (P<0.005). The positive rate of uPA in endometrial carcinoma of a stage-Ⅲpatient (89%) was obviously higher than a stage-Ⅰ(38%) patient and stage-Ⅱ(69%) patient and the difference was significant (P=0.016). The positive expression rate of uPA in the patients that muscular infiltration depth were over 1/2 was 77%, which was obviously higher than that at non-muscular lever (38%) and that was less than or equal to 1/2 (38%) (P<0.05). uPA was closely related to the clinical pathological staging of endometrial carcinoma, the degree of muscular infiltration depth and the metastasis of lymph nodes (P<0.05) and not show close relation with the pathological grading (P>0.05).
     3.The analysis of correlation between Hpa and uPA expression indicated that there were no obvious relevance (P>0.05).
     Conclusion:
     1. The expression of Hpa and uPA in endometrial adenocarcinoma was obviously higher than that of the normal endometrium, over-hyperplasia endometrium and atypical hyperplasia endometrium. The result indicated the possibility of occurrence of endometrial carcinoma.
     2. The expression of Hpa and uPA in endometrial adenocarcinoma was closely related to the clinical pathological staging, the depth of infiltration at muscular lever and the metastasis of lymph nodes and not show close relation with the pathological grading, which indicated the possible role Hpa and uPA played in the invasion and metastasis of a carcinoma and both of them may be used as reference index for biological behavior of endometrial carcinoma.
     3. Both Hpa and uPA increased in the expression of tissues of endometrial adenocarcinoma, however, there existed no obvious correlation. Further researches were needed to determine whether there existed interaction between Hpa and uPA in endometrial carcinoma.
引文
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