抑癌基因Maspin与雌激素受体在子宫内膜异位症中的表达
|
摘要
目的:子宫内膜异位症(Endometriosis EMs)以子宫内膜细胞异位生长为特征,主要影响生育年龄的妇女,是目前常见的妇科疾病之一,近年来其发病率明显增高,约占育龄期女性的10%-15%。目前,对EMs的发病机制仍不十分清楚,但EMs虽为良性病变,其某些生物学行为却类似恶性肿瘤。同时,EMs为激素依赖性疾病,异位内膜的生长和侵袭依赖于性激素。本研究通过分别检测肿瘤抑制基因Maspin及雌激素受体(Estrogen Receptor ER)在EMs患者异位子宫内膜、在位内膜和正常内膜组织中的表达,探讨Maspin在EMs发病机制中的作用,及其与ER的关系。
方法:选取2008年9月至2010年9月在秦皇岛市第一医院行经腹或腹腔镜手术治疗,术中和病理均诊断为子宫内膜异位症患者的异位子宫内膜40例(增殖期20例,分泌期20例),包括卵巢内异症病灶26例,腹膜病灶11例,宫骶韧带病灶3例。同时取所有病例的在位内膜组织(增殖期20例,分泌期20例)(同时行全子宫切除术或刮宫术)。另外,选取同期因子宫肌瘤经腹或腹腔镜行子宫切除手术患者的子宫内膜40例(增殖期20例,分泌期20例)。两组患者年龄无明显差异(P>0.05)。所有患者月经规律且无其他全身性疾病,术前6个月均未应用激素类制剂治疗。所有标本均在术后送病理科取材,并置于10%中性福尔马林固定,石蜡包埋,连续4μm切片,进行HE染色和免疫组化染色,显微镜下观察,分别记录Maspin和ER染色强度。采用统计软件SPSS13.0进行统计分析。
结果:Maspin阳性为胞核和(或)胞浆内出现均匀棕黄色颗粒;ER阳性为细胞内出现均匀棕黄色颗粒,位于细胞核内。
1 Maspin在不同子宫内膜中的表达情况:40例异位内膜组织中Maspin阳性表达17例,阴性表达23例,阳性率:42.5%;40例在位内膜组织中Maspin阳性表达20例,阴性表达20例,阳性率:50%;40例对照内膜组织中Maspin阳性表达28例,阴性表达12例,阳性率:70%。三组间阳性率比较有统计学意义(P<0.05).
进行组间比较:Maspin蛋白在异位内膜中的表达情况均低于在位内膜和对照内膜,分别与两者比较有统计学意义(P<0.05),在对照内膜中的表达情况高于在位内膜,两者比较有统计学意义(P<0.05)。
2 Maspin在各组子宫内膜中不同时期的表达:20例异位增殖期子宫内膜Maspin阳性表达率35%(7/13),20例异位分泌期子宫内膜Maspin阳性表达率50%(10/10),两组表达强度差异无统计学意义(P>0.05)。20例在位增殖期子宫内膜Maspin阳性表达率35%(7/13),20例在位分泌期子宫内膜Maspin阳性表达率65%(13/7),两组表达强度差异有统计学意义(P<0.05)。20例对照增殖期子宫内膜Maspin阳性表达率50%(10/10),20例对照分泌期子宫内膜Maspin阳性表达率90%(18/2),两组表达强度差异有统计学意义(P<0.05)。可见在对照内膜及在位内膜组中,Maspin在增殖期的表达低于分泌期,有明显差别(P <0.05),而在异位内膜组中,Maspin在增殖期和分泌期的表达无明显差别(P>0.05),说明失去了周期性变化的特点。
3 ER在不同子宫内膜中阳性率的表达情况:40例异位内膜组织中ER阳性表达25例,阴性表达15例,阳性率:62.5%;40例在位内膜组织中ER阳性表达30例,阴性表达10例,阳性率:75%;40例对照内膜组织中ER阳性表达22例,阴性表达18例,阳性率:55%。三组间阳性率比较无统计学意义(P>0.05)。.
进行组间比较:ER在异位内膜中的表达情况低于在位内膜组,两者比较有统计学意义(P<0.05);在异位内膜中的表达情况与对照内膜比较无统计学意义(P>0.05),在在位内膜中的表达情况高于对照内膜,两者比较有统计学意义(P<0.05)。
4 ER在各组子宫内膜中不同时期的表达:20例异位增殖期子宫内膜ER阳性表达率55%(11/9),20例异位分泌期子宫内膜ER阳性表达率70%(14/6),两组表达强度差异无统计学意义(P>0.05)。20例在位增殖期子宫内膜ER阳性表达率95%(19/1),20例在位分泌期子宫内膜ER阳性表达率55(11/9)%,两组表达强度差异无统计学意义(P>0.05)。20例对照增殖期子宫内膜ER阳性表达率80%(16/4),20例对照分泌期子宫内膜ER阳性表达率30%(6/14),两组表达强度差异有统计学意义(P<0.05)。在对照内膜组中,ER在增殖期的表达高于分泌期,有明显差别(P<0.05),而在异位内膜、在位内膜组中,ER在增殖期和分泌期的表达无明显差别(P>0.05),说明失去了周期性变化的特点。
5 Maspin与ER表达的相关性:异位内膜分泌期中Maspin与ER表达情况比较r:-0.580,两者呈负相关(P<0.05);异位内膜增殖期中Maspin与ER表达情况比较r:-0.273,两者无相关性(P>0.05);在位内膜分泌期中Maspin与ER表达情况比较r:-0.342,两者无相关性(P>0.05);在位内膜增殖期中Maspin与ER表达情况比较r:-0.086,两者无相关性(P>0.05);对照内膜分泌期中Maspin与ER表达情况比较r:-0.470,两者呈负相关(P<0.05);对照内膜增殖期中Maspin与ER表达情况比较r:-0.513,两者呈负相关(P<0.05).
结论:1 Maspin蛋白的表达缺失可能导致子宫内膜异位症的发生和类似肿瘤的生物学行为。
2 ER的表达异常与子宫内膜异位症的发病密切相关。
3 Maspin蛋白表达缺失和ER表达异常的相互作用可能是子宫内膜异位症发病的原因之一。
Objectice: Endometriosis(EMs) is one of common gynecological disorders, affecting 10%-15% of women during their reproductive age.At present,it still isn’t clear about the endometriosis pathogenesis.Although it is benign pathological changes,it has aggressive and evaluative behavior of malignant tumor.Moreover,EMs is a estrogen-dependent disease.Through investigate the expression and relevance of the tumor suppressor gene Maspin and Estrogen Receptor(ER) in ectopic endometrium and eutopic endometrium of patient with endometriosis(EMs) and in eutopic endometrium of patients without EMs to exploring the role of and in the pathogenesis of endometriosis.
Method:All the samples were obtained from the First Hospital of Qinhuangdao City during September 2008 to September 2010. The ectopic endometriotic endometria were obtained from 40 patients with endometriosis(proliferatice phase:n=20;secretory phase:n=20). The patients were undergoing laparotomy or laparoscopy.26 patients with ovarian endometriosia,11patients with peritoneal endometriosia,3 patients with uterosacral ligament endometriosia. The eutopic endometrium of the EMs patients were sampled by hysterectomy or curettage(proliferatice phase:n=20; secretory phase:n=20).In the same time,the control endometrial specimens were obtained from 40 patients who wasn’t diagnosed hysteromyoma (proliferatice phase:n=20;secretory phase:n=20). No difference in age was found in research group and compare group (P>0.05).None of the patients received any hormonal therapy during the 6 months before their operation.All the tissues were fixed in neutral-buffered 10% formalin solution.Then 4μm thickness paraffin-embedded sections were cut.The expression of Maspin and ER was detected by the SP immunohistochemically.The experimental dates were obtained by SPSS13.0 for windows.
Results: 1 The positice rates of Maspin in ectopic endometrium, eutopic endometrium and control group,were 42.5%,50%,70%,respectively.The expression of Maspin in ectopic endometrium of EMs is lower than eutopic endometrium(P<0.05); the expression of Maspin in ectopic endometrium of EMs is lower than control endometrium(P<0.05); the expression of Maspin in eutopic endometrium of EMs is lower than control endometrium(P<0.05).
2 There was no significant differences of the Maspin’s expression between proliferative phase and secretory phase in ectopic endometrium with EMs(P>0.05); In the eutopic endometrium with EMs and the control endometrium group, the expression of Maspin in secretory endometrium is higher than that in proliferative (both P<0.05).
3 The positice rates of ER in ectopic endometrium, eutopic endometrium and control group,were 62.5%,75%,55%,respectively.The expression of ER in ectopic endometrium of EMs is lower than eutopic endometrium(P<0.05); but there is no statistical difference between ectopic endometrium of EMs and control endometrium(P>0.05);the expression of ER in eutopic endometrium of EMs is higher than control endometrium(P<0.05).
4 There was no significant differences of the ER’s expression between proliferative phase and secretory phase both in ectopic endometrium and the eutopic endometrium with EMs(P>0.05); Expression of ER in proliferative endometrium is higher than that in secretory in contrlo endometrium (P<0.05).
5 The relationship of Maspin and ER:In the secretory phase of ectopic endometrium with EMs,the expression of Maspin was negatively correlated with ER expression (P<0.05). However,in the proliferative phase of ectopic endometrium with EMs, there was no significant correlation between expression of Maspin and ER(P>0.05).In the both secretory and proliferative phase of eutopic endometrium with EMs, there was no significant correlation between expression of Maspin and ER(P>0.05). In the both secretory and proliferative phase of control endometrium,the expression of Maspin was negatively correlated with ER expression (P<0.05).
Conclusions:1 The expression absence of Maspin is possibly induce the biological behaviour of EMs similar to malignant tumor.
2 Estrogen receptors may be responsible for the occurrence and development of EMs.
3 The upset balance between Maspin and ER maybe responsible to the pathogenesis of EMs.
方法:选取2008年9月至2010年9月在秦皇岛市第一医院行经腹或腹腔镜手术治疗,术中和病理均诊断为子宫内膜异位症患者的异位子宫内膜40例(增殖期20例,分泌期20例),包括卵巢内异症病灶26例,腹膜病灶11例,宫骶韧带病灶3例。同时取所有病例的在位内膜组织(增殖期20例,分泌期20例)(同时行全子宫切除术或刮宫术)。另外,选取同期因子宫肌瘤经腹或腹腔镜行子宫切除手术患者的子宫内膜40例(增殖期20例,分泌期20例)。两组患者年龄无明显差异(P>0.05)。所有患者月经规律且无其他全身性疾病,术前6个月均未应用激素类制剂治疗。所有标本均在术后送病理科取材,并置于10%中性福尔马林固定,石蜡包埋,连续4μm切片,进行HE染色和免疫组化染色,显微镜下观察,分别记录Maspin和ER染色强度。采用统计软件SPSS13.0进行统计分析。
结果:Maspin阳性为胞核和(或)胞浆内出现均匀棕黄色颗粒;ER阳性为细胞内出现均匀棕黄色颗粒,位于细胞核内。
1 Maspin在不同子宫内膜中的表达情况:40例异位内膜组织中Maspin阳性表达17例,阴性表达23例,阳性率:42.5%;40例在位内膜组织中Maspin阳性表达20例,阴性表达20例,阳性率:50%;40例对照内膜组织中Maspin阳性表达28例,阴性表达12例,阳性率:70%。三组间阳性率比较有统计学意义(P<0.05).
进行组间比较:Maspin蛋白在异位内膜中的表达情况均低于在位内膜和对照内膜,分别与两者比较有统计学意义(P<0.05),在对照内膜中的表达情况高于在位内膜,两者比较有统计学意义(P<0.05)。
2 Maspin在各组子宫内膜中不同时期的表达:20例异位增殖期子宫内膜Maspin阳性表达率35%(7/13),20例异位分泌期子宫内膜Maspin阳性表达率50%(10/10),两组表达强度差异无统计学意义(P>0.05)。20例在位增殖期子宫内膜Maspin阳性表达率35%(7/13),20例在位分泌期子宫内膜Maspin阳性表达率65%(13/7),两组表达强度差异有统计学意义(P<0.05)。20例对照增殖期子宫内膜Maspin阳性表达率50%(10/10),20例对照分泌期子宫内膜Maspin阳性表达率90%(18/2),两组表达强度差异有统计学意义(P<0.05)。可见在对照内膜及在位内膜组中,Maspin在增殖期的表达低于分泌期,有明显差别(P <0.05),而在异位内膜组中,Maspin在增殖期和分泌期的表达无明显差别(P>0.05),说明失去了周期性变化的特点。
3 ER在不同子宫内膜中阳性率的表达情况:40例异位内膜组织中ER阳性表达25例,阴性表达15例,阳性率:62.5%;40例在位内膜组织中ER阳性表达30例,阴性表达10例,阳性率:75%;40例对照内膜组织中ER阳性表达22例,阴性表达18例,阳性率:55%。三组间阳性率比较无统计学意义(P>0.05)。.
进行组间比较:ER在异位内膜中的表达情况低于在位内膜组,两者比较有统计学意义(P<0.05);在异位内膜中的表达情况与对照内膜比较无统计学意义(P>0.05),在在位内膜中的表达情况高于对照内膜,两者比较有统计学意义(P<0.05)。
4 ER在各组子宫内膜中不同时期的表达:20例异位增殖期子宫内膜ER阳性表达率55%(11/9),20例异位分泌期子宫内膜ER阳性表达率70%(14/6),两组表达强度差异无统计学意义(P>0.05)。20例在位增殖期子宫内膜ER阳性表达率95%(19/1),20例在位分泌期子宫内膜ER阳性表达率55(11/9)%,两组表达强度差异无统计学意义(P>0.05)。20例对照增殖期子宫内膜ER阳性表达率80%(16/4),20例对照分泌期子宫内膜ER阳性表达率30%(6/14),两组表达强度差异有统计学意义(P<0.05)。在对照内膜组中,ER在增殖期的表达高于分泌期,有明显差别(P<0.05),而在异位内膜、在位内膜组中,ER在增殖期和分泌期的表达无明显差别(P>0.05),说明失去了周期性变化的特点。
5 Maspin与ER表达的相关性:异位内膜分泌期中Maspin与ER表达情况比较r:-0.580,两者呈负相关(P<0.05);异位内膜增殖期中Maspin与ER表达情况比较r:-0.273,两者无相关性(P>0.05);在位内膜分泌期中Maspin与ER表达情况比较r:-0.342,两者无相关性(P>0.05);在位内膜增殖期中Maspin与ER表达情况比较r:-0.086,两者无相关性(P>0.05);对照内膜分泌期中Maspin与ER表达情况比较r:-0.470,两者呈负相关(P<0.05);对照内膜增殖期中Maspin与ER表达情况比较r:-0.513,两者呈负相关(P<0.05).
结论:1 Maspin蛋白的表达缺失可能导致子宫内膜异位症的发生和类似肿瘤的生物学行为。
2 ER的表达异常与子宫内膜异位症的发病密切相关。
3 Maspin蛋白表达缺失和ER表达异常的相互作用可能是子宫内膜异位症发病的原因之一。
Objectice: Endometriosis(EMs) is one of common gynecological disorders, affecting 10%-15% of women during their reproductive age.At present,it still isn’t clear about the endometriosis pathogenesis.Although it is benign pathological changes,it has aggressive and evaluative behavior of malignant tumor.Moreover,EMs is a estrogen-dependent disease.Through investigate the expression and relevance of the tumor suppressor gene Maspin and Estrogen Receptor(ER) in ectopic endometrium and eutopic endometrium of patient with endometriosis(EMs) and in eutopic endometrium of patients without EMs to exploring the role of and in the pathogenesis of endometriosis.
Method:All the samples were obtained from the First Hospital of Qinhuangdao City during September 2008 to September 2010. The ectopic endometriotic endometria were obtained from 40 patients with endometriosis(proliferatice phase:n=20;secretory phase:n=20). The patients were undergoing laparotomy or laparoscopy.26 patients with ovarian endometriosia,11patients with peritoneal endometriosia,3 patients with uterosacral ligament endometriosia. The eutopic endometrium of the EMs patients were sampled by hysterectomy or curettage(proliferatice phase:n=20; secretory phase:n=20).In the same time,the control endometrial specimens were obtained from 40 patients who wasn’t diagnosed hysteromyoma (proliferatice phase:n=20;secretory phase:n=20). No difference in age was found in research group and compare group (P>0.05).None of the patients received any hormonal therapy during the 6 months before their operation.All the tissues were fixed in neutral-buffered 10% formalin solution.Then 4μm thickness paraffin-embedded sections were cut.The expression of Maspin and ER was detected by the SP immunohistochemically.The experimental dates were obtained by SPSS13.0 for windows.
Results: 1 The positice rates of Maspin in ectopic endometrium, eutopic endometrium and control group,were 42.5%,50%,70%,respectively.The expression of Maspin in ectopic endometrium of EMs is lower than eutopic endometrium(P<0.05); the expression of Maspin in ectopic endometrium of EMs is lower than control endometrium(P<0.05); the expression of Maspin in eutopic endometrium of EMs is lower than control endometrium(P<0.05).
2 There was no significant differences of the Maspin’s expression between proliferative phase and secretory phase in ectopic endometrium with EMs(P>0.05); In the eutopic endometrium with EMs and the control endometrium group, the expression of Maspin in secretory endometrium is higher than that in proliferative (both P<0.05).
3 The positice rates of ER in ectopic endometrium, eutopic endometrium and control group,were 62.5%,75%,55%,respectively.The expression of ER in ectopic endometrium of EMs is lower than eutopic endometrium(P<0.05); but there is no statistical difference between ectopic endometrium of EMs and control endometrium(P>0.05);the expression of ER in eutopic endometrium of EMs is higher than control endometrium(P<0.05).
4 There was no significant differences of the ER’s expression between proliferative phase and secretory phase both in ectopic endometrium and the eutopic endometrium with EMs(P>0.05); Expression of ER in proliferative endometrium is higher than that in secretory in contrlo endometrium (P<0.05).
5 The relationship of Maspin and ER:In the secretory phase of ectopic endometrium with EMs,the expression of Maspin was negatively correlated with ER expression (P<0.05). However,in the proliferative phase of ectopic endometrium with EMs, there was no significant correlation between expression of Maspin and ER(P>0.05).In the both secretory and proliferative phase of eutopic endometrium with EMs, there was no significant correlation between expression of Maspin and ER(P>0.05). In the both secretory and proliferative phase of control endometrium,the expression of Maspin was negatively correlated with ER expression (P<0.05).
Conclusions:1 The expression absence of Maspin is possibly induce the biological behaviour of EMs similar to malignant tumor.
2 Estrogen receptors may be responsible for the occurrence and development of EMs.
3 The upset balance between Maspin and ER maybe responsible to the pathogenesis of EMs.
引文
1郎景和,关于子宫内膜异位症的再认识及其意义,中国工程科学,2009, 11(10): 137-142
2 Kitawaki J, Kado N, Ishihara H, Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002 Dec; 83(1-5):149-55
3 Ravenhill L, Wagstaff L, Edwards DR,G-helix of maspin mediates effects on cell migration and adhesion. J Biol Chem, 2010 Nov 19;285(47):36285-92
4 Adim SB, Filiz G, Kanat O,, Maspin expression in gastrointestinal stromal tumors. World J Surg Oncol. 2010 Mar 26;8:22
5 Khalkhali-Ellis Z. Maspin: the new frontier. Clin Cancer Res. 2006 Dec 15;12(24):7279-83
6高丽,李秀霞,肿瘤抑制基因Maspin的研究进展,疾病监测与控制杂志,2009, 3(1): 51-52
7 Narayan M, Twining S. Focus on molecules: maspin. Exp Eye Res. 2010 Jan;90(1):2-3
8 Chen EI, Florens L, Axelrod FT, Maspin alters the carcinoma proteome. FASEB J. 2005 Jul;19(9):1123-4
9 Joensuu KM, Leidenius MH, Andersson LC, High expression of maspin is associated with early tumor relapse in breast cancer. Hum Pathol. 2009 Aug;40(8):1143-51. Epub 2009 May 8
10 Rosemary Bass, Laura Wagstaff, Lorna Ravenhill, Binding of Extracellular Maspin toβ1 Integrins Inhibits Vascular Smooth Muscle Cell Migration*J Biol Chem. 2009 October 2; 284(40): 27712-27720
11 Ma Y, Peng ZL. Expression of maspin and its relation to tumor vascularization in epithelian ovarian cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Mar;40(2):223-7
12郑锦霞,肿瘤抑制基因Maspin与妇科肿瘤,国外医学妇产科学分册,2007,34(5): 314-317
13 Prasad CP, Rath G, Mathur S, Expression analysis of maspin in invasive ductal carcinoma of breast and modulation of its expression by curcumin in breast cancer cell lines. Chem Biol Interact. 2010 Feb 12;183(3):455-61
14 Hall DC, Johnson-Pais TL, Grubbs B, Maspin reduces prostate cancer metastasis to bone. Urol Oncol. 2008 Nov-Dec;26(6):652-8
15 Yoshizawa K, Nozaki S, Okamune A, Loss of maspin is a negative prognostic factor for invasion and metastasis in oral squamous cell carcinoma. J Oral Pathol Med. 2009 Jul;38(6):535-9
16 Li HW, Leung SW, Chan CS, Expression of maspin in endometrioidadenocarcinoma of endometrium. Oncol Rep. 2007 Feb;17(2):393-8
17 Sopel M, Surowiak P, Berdowska I. Nuclear maspin expression as a good prognostic factor in human epithelial ovarian carcinoma. Folia Morphol (Warsz). 2010 Nov;69(4):204-12
18 Xu C, Quddus MR, Sung CJ, Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix. Mod Pathol. 2005 Aug;18(8):1102-6
19 Surow iak P, M aterna V, Drag-Zalesinska M, Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates, Int Jgynecol Pathol, 2006. 25(2): 131-139
20 Eitel JA, Bijangi-Vishehsaraei K, Saadatzadeh MR, PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells. Cell Cycle. 2009 Mar 15;8(6):896-902
21 Zou Z, Gao C, Nagaich AK, p53 regulates the expression of the tumor suppressor gene maspin. J Biol Chem. 2000 Mar 3;275(9):6051-4
22 Nácul AP, Spritzer PM. Current aspects on diagnosis and treatment of endometriosis. Rev Bras Ginecol Obstet. 2010 Jun;32(6):298-307
23 Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest. 2006 Mar;116(3):561-70.
24 Nilsson S, Gustafsson J?. Estrogen receptors: therapies targeted to receptor subtypes. Clin Pharmacol Ther. 2011 Jan;89(1):44-55
25 Liu AJ, Guan Z, Zhang ZM, Study on expression of estrogen receptor isoforms in eutopic and ectopic endometrium of ovarian endometriosis. Zhonghua Bing Li Xue Za Zhi. 2008 Sep;37(9):584-8
26 Moen MH, Rees M, Brincat M, Erel T, EMAS position statement: Managing the menopause in women with a past history of endometriosis. Maturitas. 2010 Sep;67(1):94-7
27 Borghese B, Vaiman D, de Ziegler D, Endometriosis and genetics: what responsibility for the genes? J Gynecol Obstet Biol Reprod (Paris). 2010 May;39(3):196-207
28 Kyrou D, Kolibianakis EM, Venetis CA, Steroid receptor expression in human endometrium during the follicular phase of stimulated cycles. Hum Reprod. 2009 Nov;24(11):2931-5
29 Mohsin SK, Zhang M, Clark GM, Craig Allred D. Maspin expression in invasive breast cancer: association with other prognostic factors. J Pathol. 2003 Apr;199(4):432-5
30 Liu Z, Shi HY, Nawaz Z, Zhang M. Tamoxifen induces the expression of maspin through estrogen receptor-alpha. Cancer Lett. 2004 Jun 8;209 (1):55-65
31乔玉环,陈志华,郭瑞霞,子宫内膜癌中Maspin的表达及其与雌激素受体表达的相关性研究,现代妇产科进展2008, 17(4): 264-268
1 Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010 Jun 24;362(25):2389-98
2 Bassi MA, Podgaec S, Dias Júnior JA, Bowel endometriosis: a benign disease? Rev Assoc Med Bras. 2009 ,55(5):611-6
3郎景和,关于子宫内膜异位症的再认识及其意义,中国工程科学,2009, 11(10):137-142
4 Baldi A, Campioni M, Signorile PG. Endometriosis: pathogenesis, diagnosis, therapy and association with cancer (review). Oncol Rep. 2008 ,19(4):843-6
5 Erzen M, Rakar S, Klancnik B, Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study. Gynecol Oncol. 2001, 83(1): 100-8
6 Xu B, Hamada S, Kusuki I, Possible involvement of loss of heterozygosity in malignant transformation of ovarian endometriosis. Gynecol Oncol. 2011, 120(2):239-46
7 Kobayashi H, Kajiwara H, Kanayama S, Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review), Oncol Rep. 2009, 22(2):233-40
8 Taniguchi F, Kaponis A, Izawa M, Apoptosis and endometriosis. Front Biosci (Elite Ed). 2011 ,1(3):648-62
9 Depalo R, Cavallini A, Lorusso F, Apoptosis in normal ovaries of women with and without endometriosis. Reprod Biomed Online. 2009, 19(6): 808-15
10 Cakmak H, Guzeloglu-Kayisli O, Kayisli UA, Immune-endocrine interactions in endometriosis. Front Biosci (Elite Ed). 2009, 1:429-43
11 Vasovcak P, Senkerikova M, Hatlova J, Multiple primary malignancies and subtle mucocutaneous lesions associated with a novel PTEN gene mutation in a patient with Cowden syndrome: Case report. BMC Med Genet. 2011,12(1):38
12 Yin Y, Shen WH. PTEN: a new guardian of the genome. Oncogene. 2008, 27(41):5443-53
13 Xu B, Yao Q, Dai SZ. Detection of mutation and protein expression of PTEN gene in endometrial carcinoma. Ai Zheng. 2004,23(1):69-73
14 Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J. 2004 , 15(382):1-11
15 ViganóP, Somigliana E, Chiodo I,Molecular mechanisms and biological plausibility underlying the malignant transformation of endometriosis: a critical analysis, Hum Reprod Update. 2006 ,12(1):77-89
16 Dinulescu DM, Ince TA, Quade BJ. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med. 2005, 11(1):63-70
17 Laudanski, J. Szamatowicz, O. Kowalczuk M. Expression of selected tumor suppressor and oncogenes in endometrium of women with endometriosis Human Reproduction, 2009,13(8): 1880-1890
18张颖,王庆一,梁艳红,P53、P16、PTEN、hMLH1蛋白表达与卵巢子宫内膜异位症癌变的关系,新医学,2010,41(6):379-382
19钟蕙芳,林婧,PTEN与bcl-2、FasL在异位子宫内膜的表达及临床意义,现代妇产科进展,2010,19(2):111-114
20 Ozaki T, Nakagawara A. p53: the attractive tumor suppressor in the cancer research field. J Biomed Biotechnol. 2011;2011:603925
21 Lacroix M, Toillon RA, Leclercq G. p53 and breast cancer, an update.Endocr Relat Cancer. 2006, 13(2):293-325
22 Cuddihy AR, Jalali F, Coackley C, WTp53 induction does not override MTp53 chemoresistance and radioresistance due to gain-of-function in lung cancer cells. Mol Cancer Ther. 2008, 7(4):980-92
23 Bischoff FZ, Heard M, Simpson JL. Somatic DNA alterations in endometriosis: high frequency of chromosome 17 and p53 loss in late- stage endometriosis. J Reprod Immunol. 2002, 55(1-2):49-64
24 Akahane T, Sekizawa A, Purwosunu Y.The role of p53 mutation in the carcinomas arising from endometriosis.Int J Gynecol Pathol. 2007 Jul;26(3):345-51
25 Ribeiro Júnior CL, Arruda JT, Silva CT, Analysis of p53 codon 72 gene polymorphism in Brazilian patients with endometriosis,Genet Mol Res. 2009 May 5;8(2):494-9
26刘曼华,乔海风,陶潜,P53在子宫内膜异位症组织中表达的研究,交通医学2009,23(3):240-244
27 Chu IM, Hengst L, Slingerland JM. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer. 2008, 8(4):253-67
28 Yamamoto S, Tsuda H, Miyai K, Takano M,. Cumulative alterations of p27-related cell-cycle regulators in the development of endometriosis- associated ovarian clear cell adenocarcinoma. Histopathology. 2010 , 56(6):740-9
29 Camargo-Kosugi CM, da Silva ID, Sato H, The V109G polymorphism in the p27 gene is associated with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2009, 145(2):180-3
30 Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci. 2001, 26(1):61-6
31 Vaskivuo TE, Stenb?ck F, Karhumaa P, et al. Apoptosis and apoptosis- related proteins in human endometrium[J].Mol Cell Endocrinol. 2000, 165(1-2):75-83
32 Dufournet C, Uzan C, Fauvet R, Expression of apoptosis-related proteinsin peritoneal, ovarian and colorectal endometriosis. J Reprod Immunol. 2006, 70(1-2):151-62
33王忠泉,张品南,朱彩娥,在位与异位子宫内膜细胞凋亡及免疫组化研究,中国妇幼保健,2010, (25): 3806-3808
34王君,李斌,范颖,子宫内膜异位症患者内膜细胞中孕激素受体与凋亡因子Bcl-2、Bax表达的研究,实用妇产科杂志,2010,26(1): 45-47
35 Dufournet C, Uzan C, Fauvet R, et al. Expression of apoptosis-related proteins in peritoneal, ovarian andcolorectal endometriosis[J].J Reprod Immunol. 2006,70(1-2):151-162
36 Otsuka J, Okuda T, Sekizawa A, Amemiya S, Saito H, Okai T, Kushima M, Tachikawa T. K-ras mutation may promote carcinogenesis of endometriosis leading to ovarian clear cell carcinoma. Med Electron Microsc. 2004 ,37(3):188-92
2 Kitawaki J, Kado N, Ishihara H, Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002 Dec; 83(1-5):149-55
3 Ravenhill L, Wagstaff L, Edwards DR,G-helix of maspin mediates effects on cell migration and adhesion. J Biol Chem, 2010 Nov 19;285(47):36285-92
4 Adim SB, Filiz G, Kanat O,, Maspin expression in gastrointestinal stromal tumors. World J Surg Oncol. 2010 Mar 26;8:22
5 Khalkhali-Ellis Z. Maspin: the new frontier. Clin Cancer Res. 2006 Dec 15;12(24):7279-83
6高丽,李秀霞,肿瘤抑制基因Maspin的研究进展,疾病监测与控制杂志,2009, 3(1): 51-52
7 Narayan M, Twining S. Focus on molecules: maspin. Exp Eye Res. 2010 Jan;90(1):2-3
8 Chen EI, Florens L, Axelrod FT, Maspin alters the carcinoma proteome. FASEB J. 2005 Jul;19(9):1123-4
9 Joensuu KM, Leidenius MH, Andersson LC, High expression of maspin is associated with early tumor relapse in breast cancer. Hum Pathol. 2009 Aug;40(8):1143-51. Epub 2009 May 8
10 Rosemary Bass, Laura Wagstaff, Lorna Ravenhill, Binding of Extracellular Maspin toβ1 Integrins Inhibits Vascular Smooth Muscle Cell Migration*J Biol Chem. 2009 October 2; 284(40): 27712-27720
11 Ma Y, Peng ZL. Expression of maspin and its relation to tumor vascularization in epithelian ovarian cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Mar;40(2):223-7
12郑锦霞,肿瘤抑制基因Maspin与妇科肿瘤,国外医学妇产科学分册,2007,34(5): 314-317
13 Prasad CP, Rath G, Mathur S, Expression analysis of maspin in invasive ductal carcinoma of breast and modulation of its expression by curcumin in breast cancer cell lines. Chem Biol Interact. 2010 Feb 12;183(3):455-61
14 Hall DC, Johnson-Pais TL, Grubbs B, Maspin reduces prostate cancer metastasis to bone. Urol Oncol. 2008 Nov-Dec;26(6):652-8
15 Yoshizawa K, Nozaki S, Okamune A, Loss of maspin is a negative prognostic factor for invasion and metastasis in oral squamous cell carcinoma. J Oral Pathol Med. 2009 Jul;38(6):535-9
16 Li HW, Leung SW, Chan CS, Expression of maspin in endometrioidadenocarcinoma of endometrium. Oncol Rep. 2007 Feb;17(2):393-8
17 Sopel M, Surowiak P, Berdowska I. Nuclear maspin expression as a good prognostic factor in human epithelial ovarian carcinoma. Folia Morphol (Warsz). 2010 Nov;69(4):204-12
18 Xu C, Quddus MR, Sung CJ, Maspin expression in CIN 3, microinvasive squamous cell carcinoma, and invasive squamous cell carcinoma of the uterine cervix. Mod Pathol. 2005 Aug;18(8):1102-6
19 Surow iak P, M aterna V, Drag-Zalesinska M, Maspin expression is characteristic for cisplatin-sensitive ovarian cancer cells and for ovarian cancer cases of longer survival rates, Int Jgynecol Pathol, 2006. 25(2): 131-139
20 Eitel JA, Bijangi-Vishehsaraei K, Saadatzadeh MR, PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells. Cell Cycle. 2009 Mar 15;8(6):896-902
21 Zou Z, Gao C, Nagaich AK, p53 regulates the expression of the tumor suppressor gene maspin. J Biol Chem. 2000 Mar 3;275(9):6051-4
22 Nácul AP, Spritzer PM. Current aspects on diagnosis and treatment of endometriosis. Rev Bras Ginecol Obstet. 2010 Jun;32(6):298-307
23 Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest. 2006 Mar;116(3):561-70.
24 Nilsson S, Gustafsson J?. Estrogen receptors: therapies targeted to receptor subtypes. Clin Pharmacol Ther. 2011 Jan;89(1):44-55
25 Liu AJ, Guan Z, Zhang ZM, Study on expression of estrogen receptor isoforms in eutopic and ectopic endometrium of ovarian endometriosis. Zhonghua Bing Li Xue Za Zhi. 2008 Sep;37(9):584-8
26 Moen MH, Rees M, Brincat M, Erel T, EMAS position statement: Managing the menopause in women with a past history of endometriosis. Maturitas. 2010 Sep;67(1):94-7
27 Borghese B, Vaiman D, de Ziegler D, Endometriosis and genetics: what responsibility for the genes? J Gynecol Obstet Biol Reprod (Paris). 2010 May;39(3):196-207
28 Kyrou D, Kolibianakis EM, Venetis CA, Steroid receptor expression in human endometrium during the follicular phase of stimulated cycles. Hum Reprod. 2009 Nov;24(11):2931-5
29 Mohsin SK, Zhang M, Clark GM, Craig Allred D. Maspin expression in invasive breast cancer: association with other prognostic factors. J Pathol. 2003 Apr;199(4):432-5
30 Liu Z, Shi HY, Nawaz Z, Zhang M. Tamoxifen induces the expression of maspin through estrogen receptor-alpha. Cancer Lett. 2004 Jun 8;209 (1):55-65
31乔玉环,陈志华,郭瑞霞,子宫内膜癌中Maspin的表达及其与雌激素受体表达的相关性研究,现代妇产科进展2008, 17(4): 264-268
1 Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010 Jun 24;362(25):2389-98
2 Bassi MA, Podgaec S, Dias Júnior JA, Bowel endometriosis: a benign disease? Rev Assoc Med Bras. 2009 ,55(5):611-6
3郎景和,关于子宫内膜异位症的再认识及其意义,中国工程科学,2009, 11(10):137-142
4 Baldi A, Campioni M, Signorile PG. Endometriosis: pathogenesis, diagnosis, therapy and association with cancer (review). Oncol Rep. 2008 ,19(4):843-6
5 Erzen M, Rakar S, Klancnik B, Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study. Gynecol Oncol. 2001, 83(1): 100-8
6 Xu B, Hamada S, Kusuki I, Possible involvement of loss of heterozygosity in malignant transformation of ovarian endometriosis. Gynecol Oncol. 2011, 120(2):239-46
7 Kobayashi H, Kajiwara H, Kanayama S, Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review), Oncol Rep. 2009, 22(2):233-40
8 Taniguchi F, Kaponis A, Izawa M, Apoptosis and endometriosis. Front Biosci (Elite Ed). 2011 ,1(3):648-62
9 Depalo R, Cavallini A, Lorusso F, Apoptosis in normal ovaries of women with and without endometriosis. Reprod Biomed Online. 2009, 19(6): 808-15
10 Cakmak H, Guzeloglu-Kayisli O, Kayisli UA, Immune-endocrine interactions in endometriosis. Front Biosci (Elite Ed). 2009, 1:429-43
11 Vasovcak P, Senkerikova M, Hatlova J, Multiple primary malignancies and subtle mucocutaneous lesions associated with a novel PTEN gene mutation in a patient with Cowden syndrome: Case report. BMC Med Genet. 2011,12(1):38
12 Yin Y, Shen WH. PTEN: a new guardian of the genome. Oncogene. 2008, 27(41):5443-53
13 Xu B, Yao Q, Dai SZ. Detection of mutation and protein expression of PTEN gene in endometrial carcinoma. Ai Zheng. 2004,23(1):69-73
14 Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J. 2004 , 15(382):1-11
15 ViganóP, Somigliana E, Chiodo I,Molecular mechanisms and biological plausibility underlying the malignant transformation of endometriosis: a critical analysis, Hum Reprod Update. 2006 ,12(1):77-89
16 Dinulescu DM, Ince TA, Quade BJ. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med. 2005, 11(1):63-70
17 Laudanski, J. Szamatowicz, O. Kowalczuk M. Expression of selected tumor suppressor and oncogenes in endometrium of women with endometriosis Human Reproduction, 2009,13(8): 1880-1890
18张颖,王庆一,梁艳红,P53、P16、PTEN、hMLH1蛋白表达与卵巢子宫内膜异位症癌变的关系,新医学,2010,41(6):379-382
19钟蕙芳,林婧,PTEN与bcl-2、FasL在异位子宫内膜的表达及临床意义,现代妇产科进展,2010,19(2):111-114
20 Ozaki T, Nakagawara A. p53: the attractive tumor suppressor in the cancer research field. J Biomed Biotechnol. 2011;2011:603925
21 Lacroix M, Toillon RA, Leclercq G. p53 and breast cancer, an update.Endocr Relat Cancer. 2006, 13(2):293-325
22 Cuddihy AR, Jalali F, Coackley C, WTp53 induction does not override MTp53 chemoresistance and radioresistance due to gain-of-function in lung cancer cells. Mol Cancer Ther. 2008, 7(4):980-92
23 Bischoff FZ, Heard M, Simpson JL. Somatic DNA alterations in endometriosis: high frequency of chromosome 17 and p53 loss in late- stage endometriosis. J Reprod Immunol. 2002, 55(1-2):49-64
24 Akahane T, Sekizawa A, Purwosunu Y.The role of p53 mutation in the carcinomas arising from endometriosis.Int J Gynecol Pathol. 2007 Jul;26(3):345-51
25 Ribeiro Júnior CL, Arruda JT, Silva CT, Analysis of p53 codon 72 gene polymorphism in Brazilian patients with endometriosis,Genet Mol Res. 2009 May 5;8(2):494-9
26刘曼华,乔海风,陶潜,P53在子宫内膜异位症组织中表达的研究,交通医学2009,23(3):240-244
27 Chu IM, Hengst L, Slingerland JM. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer. 2008, 8(4):253-67
28 Yamamoto S, Tsuda H, Miyai K, Takano M,. Cumulative alterations of p27-related cell-cycle regulators in the development of endometriosis- associated ovarian clear cell adenocarcinoma. Histopathology. 2010 , 56(6):740-9
29 Camargo-Kosugi CM, da Silva ID, Sato H, The V109G polymorphism in the p27 gene is associated with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2009, 145(2):180-3
30 Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci. 2001, 26(1):61-6
31 Vaskivuo TE, Stenb?ck F, Karhumaa P, et al. Apoptosis and apoptosis- related proteins in human endometrium[J].Mol Cell Endocrinol. 2000, 165(1-2):75-83
32 Dufournet C, Uzan C, Fauvet R, Expression of apoptosis-related proteinsin peritoneal, ovarian and colorectal endometriosis. J Reprod Immunol. 2006, 70(1-2):151-62
33王忠泉,张品南,朱彩娥,在位与异位子宫内膜细胞凋亡及免疫组化研究,中国妇幼保健,2010, (25): 3806-3808
34王君,李斌,范颖,子宫内膜异位症患者内膜细胞中孕激素受体与凋亡因子Bcl-2、Bax表达的研究,实用妇产科杂志,2010,26(1): 45-47
35 Dufournet C, Uzan C, Fauvet R, et al. Expression of apoptosis-related proteins in peritoneal, ovarian andcolorectal endometriosis[J].J Reprod Immunol. 2006,70(1-2):151-162
36 Otsuka J, Okuda T, Sekizawa A, Amemiya S, Saito H, Okai T, Kushima M, Tachikawa T. K-ras mutation may promote carcinogenesis of endometriosis leading to ovarian clear cell carcinoma. Med Electron Microsc. 2004 ,37(3):188-92