凋亡抑制蛋白Survivin和Ki-67在子宫腺肌病组织中的表达及意义
摘要
目的:检测凋亡抑制蛋白Survivin及细胞核相关抗原(nuclear associated antigen, Ki-67)在子宫腺肌病(adenomyosis,AM)异位内膜、在位内膜及平滑肌组织中的表达,研究以Survivin、KI-67为核心的细胞凋亡、增殖在子宫腺肌病发病中的作用及相关意义。
方法:2004年10月至2006年10月在大连医科大学附属第一医院采用免疫组织化学S-P法检测30例子宫腺肌病标本(增殖期17例,分泌期13例)异位内膜、在位内膜、平滑肌组织及18例对照组(增殖期11例,分泌期7例)正常子宫内膜、平滑肌组织中Survivin,Ki-67蛋白表达。统计学处理采用SPSS11.5软件包行方差分析,T检验,秩和检验,秩相关分析。
结果:
1. Survivin蛋白的表达
Survivin蛋白在子宫腺肌病异位内膜、在位内膜及对照组正常子宫内膜腺上皮中均有表达,主要表达于内膜腺上皮细胞胞浆中。子宫腺肌病异位内膜腺上皮中Survivin蛋白的表达显著高于在位内膜(P=0.017,P<0.05)及对照组正常子宫内膜(P=0.000,P<0.05),子宫腺肌病在位内膜腺上皮中Survivin蛋白的表达显著高于对照组正常子宫内膜(P=0.001,P<0. 05),且这种表达的差异主要体现在增殖期子宫内膜;Survivin蛋白在子宫腺肌病异位内膜及在位内膜腺上皮增生期与分泌期表达差异均无统计学意义(P>0.05);对照组正常子宫内膜腺上皮中Survivin蛋白的表达增殖期和分泌期均为弱表达,差异亦无统计学意义(P=0.057,P>0.05)。
Survivin蛋白在三组内膜间质细胞中均呈弱表达,三组表达差异均无统计学意义(P=0.444,0.271,0.627,P>0.05),且各组增殖期和分泌期表达差异均无统计学意义(P=0.444,0.733,0.771,P>0.05)。
Survivin蛋白在子宫腺肌病及对照组平滑肌细胞中均呈弱表达,两组表达差异无统计学意义(P=0.331,0,545,P>0.05),且两组增生期与分泌期表达差异均无统计学意义(P>0.05)。
2 Ki-67的表达
Ki-67在三组内膜腺上皮中均有表达,主要表达于内膜腺上皮细胞的胞浆中。子宫腺肌病异位内膜腺上皮中Ki-67的表达显著高于在位内膜及正常子宫内膜(P=0.006,0.033,P<0.05),而在位内膜与正常内膜腺上皮Ki-67表达差异无统计学意义(P=0.622,P>0.05);Ki-67在子宫腺肌病异位内膜及在位内膜腺上皮增生期与分泌期表达差异均无统计学意义(P>0.05);对照组正常子宫内膜腺上皮中Ki-67的表达增生期与分泌期表达差异有统计学意义,增生期>分泌期(P=0.017,P<0.05)。
Ki-67在三组内膜间质细胞中表达均呈弱表达,三组表达差异均无统计学意义(P=0.507,0.698,0.818,P>0.05),且增殖期和分泌期表达差异均无统计学意义(P>0.05)。
Ki-67在子宫腺肌病及对照组平滑肌细胞中均呈弱表达,两组表达差异无统计学意义(P=0.316, P>0.05),且两组增生期与分泌期表达差异均无统计学意义(P>0.05)。
3 Survivin蛋白与Ki-67表达相关性分析
Survivin蛋白与Ki-67在子宫腺肌病异位内膜腺上皮(30例)表达经相关分析显示两者有正相关性(r=0.311, P=0.015,P<0.05)。
结论:
1.Survivin蛋白及Ki-67在子宫腺肌病组织中的过度表达可能参与了子宫腺肌病的发病过程,子宫内膜细胞凋亡、增殖失衡可能是子宫腺肌病的发病机理之一。
2.子宫腺肌病在位内膜分泌期可能更具增殖活性,并在异位内膜形成中发挥一定的作用。
3.Survivin蛋白与Ki-67在子宫腺肌病组织中的表达有正相关性,在子宫腺肌病发病机制中Survivin与Ki-67可能有一定的关联性。
Objective To investigate the expression of Survivin protein and ki-67 in eutopic and ectopic endometria and smooth muscle tissue in adenomyosis in order to study the function and relative signification of apoptosis,cell proliferation in the course of adenomyosis.
Methods Patients were random selected from the department of gynaecology and obstetrics in the first affiliated hospital of dalian medical university from October in 2004 to October in 2006.Tisstes samples included 30 samples of ectopic endometriums (17 cases in the proliferative phase,13cases in the secretory phase)and eutopoic endometriums(13cases in the proliferative phase,17cases in the secretory phase) of patients with adenomyosis, and 18 samples of normal endometrium tissues(11cases in the proliferative phase,7cases in the secretory phase). Using streptavidin-biotin peroxidase(S-P)method of the immunohistochemistry, we examined the expression of the Survivin proteins and Ki-67 in these tissues. Statistical analysis was performed by using SPSS11.5 statistics software.
Results
1.The expression of Survivin protein
There was expression of Survivin protein all together in ectopic and eutopic endometrium of adenomyosis and control’s normal endometrium which was most observed in cytoplasm of glandular epithelial cell. The expression of Survivin protein in glandular epithelial cell on ectopic endometrium of adenomyosis was significantly higher than that of eutopic endometrial and normal endometrium (P=0.017,P<0.05) , there was significant variation between the latter two groups(P=0.000,P<0.05),and these variation was mainly showed in the proliferative phase;There was nocyclic change in eutopic and ectopic endometrium of adenomyosis(P>0.05); There was small amounts expression and no cyclic change(P=0.057,P>0.05) in glandular epithelial cell on concrol’s normal endometrium.
The expression of Survivin protein in stromal cell of three groups above had no significant diffrence(P=0.507,0.698,0.818,P>0.05) and no cyclic change(P=0.444,0.733,0.771,P>0.05).
There was small amounts expression in smooth muscle cell of adenomyosis and control . There was no significant variation (P =0.331,0,545,P>0.05)and no cyclic change as well(P>0.05) between them.
2. The expression of Ki-67
There was expression of Ki-67all together in three groups above which was most observed in cytoplasm of glandular epithelial cell. The expression of Ki-67in glandular epithelial cell on ectopic endometrium of adenomyosis was significantly higher than that of eutopic endometrial and normal endometrium (P = 0.006,0.033,P<0.05), but there was no significant variation between the latter two groups(P=0.622,P>0.05); There was no cyclic change in eutopic and ectopic endometrium of adenomyosis(P>0.05), whele the expression of Ki-67 has marked vary during the menstrual cycle in concrol’s normal endometrium ,which is higher in the proliferative phase than in the secretory phase) (P=0.017,P<0.05).
The expression of Ki-67in stromal cell of three group above has no significant diffrence(P= 0.507, 0.698, 0.818, P>0.05) and no cyclic change (P>0.05).
There was small amounts expression in smooth muscle cell of adenom- yosis and control , There was no significant variation (P = 0.316, P>0.05)and no cyclic change(P>0.05) between them.
3 .There was a poor correlation between survivin and Ki-67 expression levels in 30 glandular epithelial cells on ectopic endometrium of adenom- yosis examined(r=0.311,P=0.015,P<0.05) .
Conclusion
1. The overexpression of Survivin protein and Ki-67 may take part in the formation of adenomyosis and Survivin-collected apoptosis and Ki-67-collected cell proliferation might play a pathogenic role in the development of adenomyosis.
2 The eutopic endometrium of adenomyosis in the secretory phase may be of more proliferative ability and may play important role in the format- ion of ectopic endometrium .
3 The association of the expression of Survivin protein and Ki-67 in glandular epithelial cell on eutopic and ectopic endometrium of adenomy- osis may be of occurrence in one of adenomyosis pathogenesis.
方法:2004年10月至2006年10月在大连医科大学附属第一医院采用免疫组织化学S-P法检测30例子宫腺肌病标本(增殖期17例,分泌期13例)异位内膜、在位内膜、平滑肌组织及18例对照组(增殖期11例,分泌期7例)正常子宫内膜、平滑肌组织中Survivin,Ki-67蛋白表达。统计学处理采用SPSS11.5软件包行方差分析,T检验,秩和检验,秩相关分析。
结果:
1. Survivin蛋白的表达
Survivin蛋白在子宫腺肌病异位内膜、在位内膜及对照组正常子宫内膜腺上皮中均有表达,主要表达于内膜腺上皮细胞胞浆中。子宫腺肌病异位内膜腺上皮中Survivin蛋白的表达显著高于在位内膜(P=0.017,P<0.05)及对照组正常子宫内膜(P=0.000,P<0.05),子宫腺肌病在位内膜腺上皮中Survivin蛋白的表达显著高于对照组正常子宫内膜(P=0.001,P<0. 05),且这种表达的差异主要体现在增殖期子宫内膜;Survivin蛋白在子宫腺肌病异位内膜及在位内膜腺上皮增生期与分泌期表达差异均无统计学意义(P>0.05);对照组正常子宫内膜腺上皮中Survivin蛋白的表达增殖期和分泌期均为弱表达,差异亦无统计学意义(P=0.057,P>0.05)。
Survivin蛋白在三组内膜间质细胞中均呈弱表达,三组表达差异均无统计学意义(P=0.444,0.271,0.627,P>0.05),且各组增殖期和分泌期表达差异均无统计学意义(P=0.444,0.733,0.771,P>0.05)。
Survivin蛋白在子宫腺肌病及对照组平滑肌细胞中均呈弱表达,两组表达差异无统计学意义(P=0.331,0,545,P>0.05),且两组增生期与分泌期表达差异均无统计学意义(P>0.05)。
2 Ki-67的表达
Ki-67在三组内膜腺上皮中均有表达,主要表达于内膜腺上皮细胞的胞浆中。子宫腺肌病异位内膜腺上皮中Ki-67的表达显著高于在位内膜及正常子宫内膜(P=0.006,0.033,P<0.05),而在位内膜与正常内膜腺上皮Ki-67表达差异无统计学意义(P=0.622,P>0.05);Ki-67在子宫腺肌病异位内膜及在位内膜腺上皮增生期与分泌期表达差异均无统计学意义(P>0.05);对照组正常子宫内膜腺上皮中Ki-67的表达增生期与分泌期表达差异有统计学意义,增生期>分泌期(P=0.017,P<0.05)。
Ki-67在三组内膜间质细胞中表达均呈弱表达,三组表达差异均无统计学意义(P=0.507,0.698,0.818,P>0.05),且增殖期和分泌期表达差异均无统计学意义(P>0.05)。
Ki-67在子宫腺肌病及对照组平滑肌细胞中均呈弱表达,两组表达差异无统计学意义(P=0.316, P>0.05),且两组增生期与分泌期表达差异均无统计学意义(P>0.05)。
3 Survivin蛋白与Ki-67表达相关性分析
Survivin蛋白与Ki-67在子宫腺肌病异位内膜腺上皮(30例)表达经相关分析显示两者有正相关性(r=0.311, P=0.015,P<0.05)。
结论:
1.Survivin蛋白及Ki-67在子宫腺肌病组织中的过度表达可能参与了子宫腺肌病的发病过程,子宫内膜细胞凋亡、增殖失衡可能是子宫腺肌病的发病机理之一。
2.子宫腺肌病在位内膜分泌期可能更具增殖活性,并在异位内膜形成中发挥一定的作用。
3.Survivin蛋白与Ki-67在子宫腺肌病组织中的表达有正相关性,在子宫腺肌病发病机制中Survivin与Ki-67可能有一定的关联性。
Objective To investigate the expression of Survivin protein and ki-67 in eutopic and ectopic endometria and smooth muscle tissue in adenomyosis in order to study the function and relative signification of apoptosis,cell proliferation in the course of adenomyosis.
Methods Patients were random selected from the department of gynaecology and obstetrics in the first affiliated hospital of dalian medical university from October in 2004 to October in 2006.Tisstes samples included 30 samples of ectopic endometriums (17 cases in the proliferative phase,13cases in the secretory phase)and eutopoic endometriums(13cases in the proliferative phase,17cases in the secretory phase) of patients with adenomyosis, and 18 samples of normal endometrium tissues(11cases in the proliferative phase,7cases in the secretory phase). Using streptavidin-biotin peroxidase(S-P)method of the immunohistochemistry, we examined the expression of the Survivin proteins and Ki-67 in these tissues. Statistical analysis was performed by using SPSS11.5 statistics software.
Results
1.The expression of Survivin protein
There was expression of Survivin protein all together in ectopic and eutopic endometrium of adenomyosis and control’s normal endometrium which was most observed in cytoplasm of glandular epithelial cell. The expression of Survivin protein in glandular epithelial cell on ectopic endometrium of adenomyosis was significantly higher than that of eutopic endometrial and normal endometrium (P=0.017,P<0.05) , there was significant variation between the latter two groups(P=0.000,P<0.05),and these variation was mainly showed in the proliferative phase;There was nocyclic change in eutopic and ectopic endometrium of adenomyosis(P>0.05); There was small amounts expression and no cyclic change(P=0.057,P>0.05) in glandular epithelial cell on concrol’s normal endometrium.
The expression of Survivin protein in stromal cell of three groups above had no significant diffrence(P=0.507,0.698,0.818,P>0.05) and no cyclic change(P=0.444,0.733,0.771,P>0.05).
There was small amounts expression in smooth muscle cell of adenomyosis and control . There was no significant variation (P =0.331,0,545,P>0.05)and no cyclic change as well(P>0.05) between them.
2. The expression of Ki-67
There was expression of Ki-67all together in three groups above which was most observed in cytoplasm of glandular epithelial cell. The expression of Ki-67in glandular epithelial cell on ectopic endometrium of adenomyosis was significantly higher than that of eutopic endometrial and normal endometrium (P = 0.006,0.033,P<0.05), but there was no significant variation between the latter two groups(P=0.622,P>0.05); There was no cyclic change in eutopic and ectopic endometrium of adenomyosis(P>0.05), whele the expression of Ki-67 has marked vary during the menstrual cycle in concrol’s normal endometrium ,which is higher in the proliferative phase than in the secretory phase) (P=0.017,P<0.05).
The expression of Ki-67in stromal cell of three group above has no significant diffrence(P= 0.507, 0.698, 0.818, P>0.05) and no cyclic change (P>0.05).
There was small amounts expression in smooth muscle cell of adenom- yosis and control , There was no significant variation (P = 0.316, P>0.05)and no cyclic change(P>0.05) between them.
3 .There was a poor correlation between survivin and Ki-67 expression levels in 30 glandular epithelial cells on ectopic endometrium of adenom- yosis examined(r=0.311,P=0.015,P<0.05) .
Conclusion
1. The overexpression of Survivin protein and Ki-67 may take part in the formation of adenomyosis and Survivin-collected apoptosis and Ki-67-collected cell proliferation might play a pathogenic role in the development of adenomyosis.
2 The eutopic endometrium of adenomyosis in the secretory phase may be of more proliferative ability and may play important role in the format- ion of ectopic endometrium .
3 The association of the expression of Survivin protein and Ki-67 in glandular epithelial cell on eutopic and ectopic endometrium of adenomy- osis may be of occurrence in one of adenomyosis pathogenesis.
引文
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22. Bruno S, Darzynkiewicz Z. Cell cycle dependent expression and stability of the nuclear protein detocted by Ki-67 antibidy in HL-60 cell. Cell prolif.1992; 25; 31-40
23. Jones RK, Bulmer JN, Searle RF. Immunofistochemical characterization of proliferation, oestrogen receptor and progesterone receptor expression in endometriosis; comparison of eutopic and ectopic endometrium with normal cycling endometrium. Human Reproduction.1995;10(12);3272-3279.
24. Tabibzadeh S. Immunoreactivity of human endometrium:correlation with end- ometrial dating.Fertil Steril,1990;54(4):624-631.
25. BourlevVA, Pavlovitch SV, Volkov NI et al.ki-67Expression in the Endometrium of Healthy Women and Patients with Peritoneal Endometriosis.International Journal of Gynecology and Obstetrics.2000,70(3):92
26. 薛晴,周应芳,刘运明等.子宫内膜细胞增生相关核抗原 KI-67 和 CA125 在子宫腺肌病组织中的表达.实用妇产科杂志.2003;19(5)292-294
27. Matsumoto Y, Iwasaka T, Yamasaki F, el al. Apoptosis and KI-67 expression in adenomyotic lesions and in the corresponding eutopic endometrium. Obstet Gynecol,1999,94(1):71-77.
28. eresman GF, Auge L, Baranao RI, Oral contraceptives suppress cell prolifer- ation and enhance apoptosis of eutopic endometrial tissue from patients with endometriosis. Fertil Steril. 2002 Jun;77(6):1141-1147.
29. Toki T, Kubota J, Lu X, Immunohistochemical analysis of CA125, CA19-9, and Ki-67 in stage III or IVendometriosis: positive correlation between serum CA125 level and endometriotic epithelial cell proliferation. Acta Obstet Gynecol Scand. 2000 Sep;79(9):771-776.
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21. 王莉,李青,郭暧林等 .增殖核抗原、热休克蛋白 70 在星形胶质细胞瘤组织中的表达和意义 [J]. 陕西肿瘤医学,2002, 10(2):85-87
22. Bruno S, Darzynkiewicz Z. Cell cycle dependent expression and stability of the nuclear protein detocted by Ki-67 antibidy in HL-60 cell. Cell prolif.1992; 25; 31-40
23. Jones RK, Bulmer JN, Searle RF. Immunofistochemical characterization of proliferation, oestrogen receptor and progesterone receptor expression in endometriosis; comparison of eutopic and ectopic endometrium with normal cycling endometrium. Human Reproduction.1995;10(12);3272-3279.
24. Tabibzadeh S. Immunoreactivity of human endometrium:correlation with end- ometrial dating.Fertil Steril,1990;54(4):624-631.
25. BourlevVA, Pavlovitch SV, Volkov NI et al.ki-67Expression in the Endometrium of Healthy Women and Patients with Peritoneal Endometriosis.International Journal of Gynecology and Obstetrics.2000,70(3):92
26. 薛晴,周应芳,刘运明等.子宫内膜细胞增生相关核抗原 KI-67 和 CA125 在子宫腺肌病组织中的表达.实用妇产科杂志.2003;19(5)292-294
27. Matsumoto Y, Iwasaka T, Yamasaki F, el al. Apoptosis and KI-67 expression in adenomyotic lesions and in the corresponding eutopic endometrium. Obstet Gynecol,1999,94(1):71-77.
28. eresman GF, Auge L, Baranao RI, Oral contraceptives suppress cell prolifer- ation and enhance apoptosis of eutopic endometrial tissue from patients with endometriosis. Fertil Steril. 2002 Jun;77(6):1141-1147.
29. Toki T, Kubota J, Lu X, Immunohistochemical analysis of CA125, CA19-9, and Ki-67 in stage III or IVendometriosis: positive correlation between serum CA125 level and endometriotic epithelial cell proliferation. Acta Obstet Gynecol Scand. 2000 Sep;79(9):771-776.
30. Toki T, Horiuchi A, Li SF, Proliferative activity of postmenopausal endom- etrosis :a histopathologic and immunocytochemical stydy. Int J Gynecol Pathol.1996;15(1):45-53.
31. 宋坚红,程忠平等.ER PR、PCNA、C-erb-B2 在子宫腺肌病标本的表达现象[J]四川医学 2003,10(24): 1039-1040
32. Ogawa S,Kaku T, Amada S, Ovarian endometriosis associated with ovarian carcinoma:a clinicopathological and immunohistochemical study [J].Gynecol Oncol.2000;77(2):298-304.
33. Han AC,Hovenden S,Rosenblum NG,Adenocarcinoma arising in extragonadal endometriosis :an immunohistochemical study.Cancer.1998 15;83(6):1163-1169.
34. Hall PA, Levison DA,Woods AL,et al.Proliferating cell nuclear antigen(PCNA) mmunolocalization in paraffin sections:an index of cell proliferation with evidence of deregulated expression in some neoplasms[J].J Pathol,1990,162(4):285