Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium

To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ERalpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.     

Bcl-2和Bax蛋白在正常、增生和恶性子宫内膜中的表达

Objective To investigate the expression of Bcl-2 and Bax proteins in normal, hyperplastic, and malignant endometrium. Methods Endometrial tissues were obtained from 14 proliferative endometrial samples; simple (n=30) and complex hyperplasia without atypia (n=13); complex hyperplasia with atypia (n=20) and endometrial adenocarcinoma (n=17). The expression of Bcl-2 and Bax proteins was detected by using immunohistochemical staining with appropriate antibodies. Results The intensity of Bcl-2 staining was gradually increased from proliferative to simple and complex hyperplasia, but it was gradually decreased from atypia hyperplasia to endometrial adenocarcinoma (P<0.05). The intensity of Bax staining was gradually increased from proliferative endometrium to simple and complex hyperplasia, but in atypia hyperplasia it was obviously lower than simple hyperplasia, the ratio of Bcl-2: Bax staining intensity was changed with the endometrium from proliferative, hyperplastic endometrium to endometrial adenocarcinoma. The ratio of Bcl-2: Bax staining intensity was obviously decreased in atypia hyperplasia and endometrial adenocarcinoma. Conclusion The survival time of the cells in hyperplasia expressing Bcl-2 might be prolonged. Neoplastic cells in atypia hyperplasia and adenocarcinoma might show a decreased expression of Bcl-2 and Bax, suggesting that Bcl-2 and Bax might be important indexes and prognosis factors and the expression of Bcl-2 and Bax might be correlated with carcinogenesis in the uterine endometrium of humans.     

c—myc和p16在子宫内膜癌中的表达及临床意义

目的 研究癌基因c-myc和抑癌基因p16在子宫内膜癌中的表达及临床意义。方法采用免疫组化(S-P)法检测10例增生子宫内膜、22例子宫内膜不典型增生、42例子宫内膜癌中c-myc和p16基因表达,并分析其与子宫内膜癌发生、发展及预后的关系。结果 (1)c-myc在子宫内膜癌中的阳性率为26.19％(11/42),显著高于增生子宫内膜(均显阴性)及子宫内膜不典型增生(4.55％;P<0.05,P<0.05);c-myc在子宫内膜癌中的表达与组织学分级、临床分期显著相关(P<0.01,P<0.05),但与肌层浸润深度及淋巴结转移无关(P>0.05,P>0.05)。(2)p16在子宫内膜癌的阳性率为69.05％(29/42),显著低于增生子宫内膜(100％,10/10)及子宫内膜不典型增生(90.91％,;P<0.05,P<0.05);p16的表达与组织学分级、肌层浸润深度、临床分期及淋巴结转移显著相关(P<0.05,P<0.05,P<0.01,P<0.05)。结论 癌基因c-myc和抑癌基因p16可能在子宫内膜癌的发生、发展及转归中起着重要作用。     

p53、p21ras、nm23-H1基因在子宫内膜癌中表达与临床病理关系研究

 目的　研究p53、p21ras、nm23-H1基因在子宫内膜癌中的表达与临床病理学关系。方法　应用免疫组织化学方法(SABC法)研究18例正常增生期子宫内膜、12例子宫内膜非典型性增生过长、78例子宫内膜癌的p53、p21ras、nm23-H1基因的表达情况。结果　12例增生期子宫内膜中p53和p21ras基因表达阴性,3例子宫内膜非典型性增生过长中p53阳性;p53、p21ras、nm23基因在子宫内膜癌中表达率分别为57.69%,55.12%,71.79%;p53的表达在不同的临床分期,病理学分级,有无淋巴结转移和是否绝经之间差异有显著性意义(P<0.01);p21ras基因表达与病理学分级及有无淋巴结转移有关(P<0.05),但与临床分期无关;nm23-H1的表达与病理学分级,临床分期,有无淋巴结转移有关。结论　p53、p21ras、nm23基因在子宫内膜癌中均高表达,p53的表达和肿瘤发生,发展有关,p21ras基因表达与肿瘤的进展有关,nm23的表达与淋巴结转移呈负相关。     

BCL-2 and P53 expression in endometrial carcinoma

Our aim was to compare the results of bcl-2 expression in endometrial carcinoma with clinicopathological prognostic factors along with p53 accumulation. In addition, p53 expression was compared to different subtypes of endometrial carcinoma. Immunohistochemical staining was performed on formalin-fixed, paraffin embedded tissue sections by using Bcl-2 Supersensitive Mouse Anti-Bcl-2 Oncoprotein (Biogenex AM287-5M) for bcl-2 immunostaining and Supersensitive Mouse Anti-p53 Suppressor Gene Product (1801) (Biogenex AM 240-5M) for p53 immunostaining. 9 out of 9 cases of proliferative endometrium, 5/5 cases of endometrial hyperplasia without atypia, 5/5 cases with atypia, and 21/35 cases of endometrial carcinoma showed bcl-2 protein expression. Bcl-2 expression was not related to age, surgical stage, or histopathological features, nor was there an inverse correlation between bcl-2 and p53 expression in endometrial carcinoma. p53 expression was detected in 3/4 cases of serous papillary carcinoma, whereas only 5/31 cases of endometrioid carcinoma showed p53 expression. Bcl-2 expression decreased in endometrial carcinomas, and mechanisms other than p53 may play a role in the regulation of bcl-2 expression in endometrial carcinoma. Abnormal p53 protein expression is an important event in the development of serous tumors, which may explain partly why they are more aggressive than their endometrioid counterparts where p53 expression does not play a major role.     

p53、p21ras、nm23-H1基因在子宫内膜癌中表达与临床病理关系研究

目的　研究p53、p2 1ras、nm2 3 H1基因在子宫内膜癌中的表达与临床病理学关系。方法　应用免疫组织化学方法 (SABC法 )研究 18例正常增生期子宫内膜、12例子宫内膜非典型性增生过长、78例子宫内膜癌的p53、p2 1ras、nm2 3 H1基因的表达情况。结果　 12例增生期子宫内膜中p53和p2 1ras基因表达阴性 ,3例子宫内膜非典型性增生过长中p53阳性 ;p53、p2 1ras、nm2 3基因在子宫内膜癌中表达率分别为 57 69% ,55 12 % ,71 79% ;p53的表达在不同的临床分期 ,病理学分级 ,有无淋巴结转移和是否绝经之间差异有显著性意义 (P <0 0 1) ;p2 1ras基因表达与病理学分级及有无淋巴结转移有关 (P <0 0 5) ,但与临床分期无关 ;nm2 3 H1的表达与病理学分级 ,临床分期 ,有无淋巴结转移有关。结论　p53、p2 1ras、nm2 3基因在子宫内膜癌中均高表达 ,p53的表达和肿瘤发生 ,发展有关 ,p2 1ras基因表达与肿瘤的进展有关 ,nm2 3的表达与淋巴结转移呈负相关。     

Metalloproteinase-2, -7 and -9 and tissue inhibitor of metalloproteinase-1 and -2 expression in normal, hyperplastic and neoplastic endometrium: a clinical-pathological correlation study.

BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors are key-players in extracellular matrix and basement membrane degradation, and are involved in both physiological and malignant processes. The aim of this study was to examine MMP-2, -7 and -9 and TIMP-1 and -2 expression in normal, hyperplastic and malignant endometrium, and their relation to clinical and histological prognostic factors. MATERIALS AND METHODS: We performed qualitative and semi-quantitative immunohistochemical analysis of 20 samples of normal endometrium (10 in the proliferative phase, 10 in the secretory phase), 39 samples of hyperplastic endometrium (17 without atypia and 22 with atypia) and 38 samples of endometrioid carcinoma, by using specific monoclonal antibodies. RESULTS: In normal endometrium, epithelial expression of MMP-2 (P = 0.0007), MMP-7 (P = 0.0002) and TIMP-2 (P = 0.0004) was increased during the proliferative phase of the menstrual cycle. MMP-2 expression correlated negatively with TIMP-2 expression (P = 0.001, rho = 0.702). Endometrial stromal cells in the secretory phase showed strong MMP-2 expression (P = 0.004) and weak MMP-7 (P = 0.001) and TIMP-1 expression (P = 0.01). In hyperplastic endometrium, the presence of atypia was associated with lower TIMP-2 expression (P = 0.005) and was also associated with a trend towards higher MMP-2 expression. Endometrial stromal cell expression of MMP-2, -7 and -9 and TIMP-1 and -2 did not differ between hyperplastic endometrium with and without atypia. A gradient of MMP-2 and -9 expression was observed from hyperplastic endometrium to endometrial carcinomas. In endometrial carcinomas, MMP-2 expression increased (P = 0.0004) and TIMP-2 expression decreased (P = 0.0005) with the histological grade. TIMP-2 expression correlated with myometrial invasion (P = 0.005), lymphovascular space involvement (P = 0.008) and lymph node involvement (P = 0.007). CONCLUSION: These results support the involvement of MMPs and TIMPs in endometrial carcinogenesis. Strong MMP-2 and weak TIMP-2 expression were the most potent markers of endometrial malignancies with a high risk of local and distant spread.     

p16、Cyclin D1和COX-2蛋白在子宫内膜不同增生性病变中的表达及意义

 目的 探讨p16、Cyclin D1及COX-2蛋白在子宫内膜的癌前病变及子宫内膜样腺癌中的诊断价值。 方法 采用免疫组织化学SP法,对131例不同增生性子宫内膜病变组织中p16、Cyclin D1及COX-2蛋白 的表达进行检测,并对子宫内膜样腺癌发病新模式的不同阶段3种蛋白的表达进行对比观察。 结果 （1）根据EIN组织学诊断及分类标准,在94例子宫内膜增生病例中共检出EIN病例26例,其余 68例为良性子宫内膜增生病例。（2）p16和Cyclin D1蛋白在增殖期子宫内膜、良性子宫内膜 增生、EIN及子宫内膜样腺癌4组中的阳性表达率及高表达率均无明显差异（ P 均>0.05）。（ 3）COX-2蛋白在正常增殖期子宫内膜组织中不表达;在EIN和子宫内膜样腺癌组阳性表达率及 高表达率均分别显著高于增殖期子宫内膜和良性子宫内膜增生组（ P 均<0.01）,而两组间在 阳性表达率和高表达率上均无明显差异（ P 均>0.05）。 结论 与p16、Cyclin D1蛋白表达相比,COX-2 蛋白的高表达在子宫内膜样腺癌的发生过程中可能是 一种早期分子事件。其表达在鉴别良性子宫内膜增生和EIN、子宫内膜样腺癌方面可能是一种 有用的肿瘤性标志物。     

Frequent loss of expression of the cyclin-dependent kinase inhibitor p27(Kip1) in estrogen-related Endometrial adenocarcinomas.

PURPOSE: p27(Kip1) is a member of the Cip1/Kip1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. Low levels of p27 are associated with poor prognosis in a variety of gynecological tumors, including breast, ovarian, and cervical carcinomas. The role of p27 in endometrial cancer remains controversial. EXPERIMENTAL DESIGN: In the present study, p27 protein expression was investigated by immunohistochemistry in a series of 217 endometrial adenocarcinomas and, where present, in synchronous normal endometrium, simple and complex hyperplasia (with or without atypia), and cystic atrophy. The relationship between p27 expression and clinical outcome was also evaluated. RESULTS: Immunohistochemical analysis revealed a significant loss of p27 expression from normal (33%) through hyperplastic endometrium (50%) to endometrial adenocarcinomas (71%; P 相似文献   

端粒酶hTERT在子宫内膜癌中的表达及意义探讨

目的　探讨端粒酶hTERT基因蛋白表达与子宫内膜癌发生发展的关系及对内膜癌诊断、预后的临床意义。方法　采用免疫组化方法对 33例子宫内膜癌、36例绝经期子宫内膜及 36例子宫内膜增生过长标本进行端粒酶hTERT、雌激素受体ER及孕激素受体PR检测 ,同时与正常增殖期 ,分泌期子宫内膜进行对照。结果　hTERT在子宫内膜癌中的表达强度明显高于其他内膜病变 ,有显著性差异 (P<0 .0 5 ) ;hTERT在子宫内膜癌中的表达与肌层浸润及临床分期呈正相关 ;与病理分级及雌、孕激素受体ER ,PR呈负相关。结论　上述结果提示端粒酶hTERT在子宫内膜癌的发生发展中可能起重要作用 ,端粒酶hTERT与ER ,PR的联合检测可能成为子宫内膜癌判断预后的一个指标。     

Importin 13在子宫内膜异位症和子宫内膜癌中的表达及意义

背景与目的:正常情况下的子宫内膜干/祖细胞有助于子宫内膜的生理性修复,而子宫内膜干/祖细胞的异常增殖和异常分化则会导致子宫内膜疾病(如子宫内膜异位症和子宫内膜癌)。Importin 13(IPO13)是importinβ家族新成员的一个核质双向的转运受体蛋白,是角膜上皮干细胞的一个标记,在维持干细胞的性状、高增殖潜力、低分化状态,调节细胞分化以及小鼠生殖细胞减数分裂上具有重要的作用。本文探讨成体干细胞标记IPO13在子宫内膜异位症和子宫内膜癌中的表达及意义。方法:手术取正常子宫内膜组织40例(对照组),其中增生期和分泌期各20例,异位子宫内膜组织20例(异位症组)和子宫内膜癌病灶组织20例(内膜癌组)。采用免疫组化SP法检测IPO13蛋白在细胞内的定位;采用实时荧光定量PCR技术(real-time quantitativepolymerase chain reaction,RT-PCR)检测IPO13 mRNA的表达;Western blot检测IPO13蛋白的表达。结果:IPO13蛋白在内膜癌、异位症及正常对照组中腺上皮细胞和间质细胞的细胞质和细胞核中均有表达。IPO13蛋白在对照组增生期表达量(0.52±0.30)明显高于分泌期(0.25±0.04,P<0.05);IPO13蛋白在异位症组表达量(0.81±0.12)明显高于对照组增生期及分泌期(P<0.05);IPO13蛋白在内膜癌组表达量(1.21±0.11)明显高于异位症组(P<0.05)。IPO13 mRNA在对照组增生期表达量是分泌期的3倍(P<0.05);IPO13 mRNA在异位症组中表达量是对照组分泌期的6倍(P<0.05),增生期的2.5倍(P<0.05);IPO13 mRNA在内膜癌组表达量是异位症组的2倍(P<0.05)。结论:IPO13在子宫内膜癌中及异位症组中表达明显高于对照组,推测其高表达与子宫内膜癌及子宫内膜异位症发病密切相关。     

Diagnostic utility of phosphatase and tensin homolog, β‐catenin,and p53 for endometrial carcinoma by thin‐layer endometrial preparations

BACKGROUND.

For the current report, the authors examined the characteristic features of morphology and molecular biology of phosphatase and tensin homolog (PTEN), β‐catenin, and p53 immunocytochemistry in endometrial carcinoma by using thin‐layer cytologic preparations.

METHODS.

During a 6‐month period, 120 endometrial samples were collected directly by using the Uterobrush, and thin‐layer specimens were prepared. Immunocytochemical expression levels of PTEN, β‐catenin, and p53 were investigated by using 40 specimens of endometrial carcinoma (EC), and 30 specimens each of proliferative endometrium, secretory endometrium, and atrophic endometrium.

RESULTS.

For PTEN immunoreactivity, the a cutoff value of 50% PTEN expression appeared to be useful for the correct diagnosis of EC in endometrial cytology. For β‐catenin immunoreactivity, an increase in cytoplasmic and nuclear β‐catenin expression and a loss of β‐catenin expression appeared to be useful for the correct diagnosis of EC in endometrial cytology and may aid in the stratification of EC into low grade and high grade EC. For p53 immunoreactivity, the application of a cutoff score ≥4 for nuclear p53 expression appeared to be useful for the diagnosis of high‐grade EC in endometrial cytology.

CONCLUSIONS.

Immunocytochemical findings from a combination of PTEN, β‐catenin, and p53, in addition to cytomorphologic features, appeared to be useful for the more accurate diagnosis of EC in endometrial cytology. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

p27蛋白在子宫内膜癌的表达及意义

目的:探讨p27蛋白在子宫内膜癌的表达及意义。方法:应用免疫组化,检测12例增生期子宫内膜,10例子宫内膜非典型增生及42例子宫内膜样腺癌标本中p27蛋白的表达。结果:p27蛋白在增生期子宫内膜、子宫内膜非典型增生及子宫内膜癌中的阳性表达率逐渐降低,分别为100%、60%和40.47%。随子宫内膜癌临床分期的升高、病理分级的降低及肌层浸润的加深,p27蛋白的表达呈逐渐降低的趋势。结论:p27蛋白低表达可能与子宫内膜癌的不良预后有关。     

ezrin和flt-1在子宫内膜癌中的表达及其意义

目的探讨膜细胞骨架连接蛋白ezrin、血管内皮生长因子受体1（flt-1）在子宫内膜癌中的表达及其与临床病理参数之间的关系.方法采用免疫组化方法检测79例子宫内膜癌和12例转移灶组织中ezrin和flt-1蛋白的表达,选择不典型增生14例,单纯、复合性增生20例和正常子宫内膜增生期15例作为对照.结果 ezrin蛋白在正常内膜,单纯、复合性增生, 不典型增生和内膜癌四组间的差异有显著性（P＜0.01）,不典型增生组ezrin的表达高于单纯、复合性增生,内膜癌高于不典型增生.多数正常和增生腺上皮细胞不表达ezrin,而大多数不典型增生和内膜癌细胞表达ezrin,且为细胞浆和细胞膜弥散着色,差异有显著性.内膜癌中,深肌层浸润组ezrin的表达高于浅肌层或无肌层浸润组（P＜0.05）.flt-1在不典型增生中的表达高于正常内膜,内膜癌中flt-1的表达强度随组织学分级升高而降低（P＜0.05）.内膜癌中ezrin与flt-1的表达间无明显相关性,ezrin与雌激素受体（ER）间存在负相关.结论 ezrin可能参与了子宫内膜癌的发生和演进过程.     

子宫内膜息肉细胞凋亡及增殖的研究

 目的　从细胞凋亡与增殖方面探讨子宫内膜息肉的发病机制,解释其临床症状。方法　免疫组织化学方法与计算机图像分析系统定量检测bcl-2、Bax、Ki-67表达,计算Bax／bcl-2 比值。对比分析增殖期息肉（40例）与增殖期内膜（40例）之间、分泌期息肉（40例）与分泌期内膜（40例）之间表达情况,腺上皮与间质分别对照。结果　Ki-67在不论是增殖期还是分泌期腺上皮细胞中,息肉组显著高于对照内膜组（P＜0.01）,而在间质中息肉组低于对照内膜组（P＝0.000）。Bax在增殖期息肉腺上皮的表达高于增殖期内膜腺上皮。bcl-2在分泌期息肉与分泌期内膜之间不论是腺上皮还是间质,均是前者高于后者。不管是分泌期还是增殖期,间质Bax／bcl-2在息肉组显著低于内膜组。结论　子宫内膜息肉的发生可能与腺上皮细胞过度增生及间质细胞凋亡受限有关。息肉增殖、凋亡及脱落与周围内膜不同步,且息肉内部本身增殖、凋亡不同步,两个不同步导致不规则、经间期出血的临床表现。     

Diagnostic utility of phosphatase and tensin homolog, beta-catenin, and p53 for endometrial carcinoma by thin-layer endometrial preparations

BACKGROUND: For the current report, the authors examined the characteristic features of morphology and molecular biology of phosphatase and tensin homolog (PTEN), beta-catenin, and p53 immunocytochemistry in endometrial carcinoma by using thin-layer cytologic preparations. METHODS: During a 6-month period, 120 endometrial samples were collected directly by using the Uterobrush, and thin-layer specimens were prepared. Immunocytochemical expression levels of PTEN, beta-catenin, and p53 were investigated by using 40 specimens of endometrial carcinoma (EC), and 30 specimens each of proliferative endometrium, secretory endometrium, and atrophic endometrium. RESULTS: For PTEN immunoreactivity, the a cutoff value of 50% PTEN expression appeared to be useful for the correct diagnosis of EC in endometrial cytology. For beta-catenin immunoreactivity, an increase in cytoplasmic and nuclear beta-catenin expression and a loss of beta-catenin expression appeared to be useful for the correct diagnosis of EC in endometrial cytology and may aid in the stratification of EC into low grade and high grade EC. For p53 immunoreactivity, the application of a cutoff score >or=4 for nuclear p53 expression appeared to be useful for the diagnosis of high-grade EC in endometrial cytology. CONCLUSIONS: Immunocytochemical findings from a combination of PTEN, beta-catenin, and p53, in addition to cytomorphologic features, appeared to be useful for the more accurate diagnosis of EC in endometrial cytology.     

细胞核增殖相关抗原Ki67在子宫内膜病变中的表达

目的：研究Ki67抗原在子宫内膜病变中表达的规律及其在子宫内膜癌的发生和预后评估的临床价值。方法：用免疫组化（SP）法检测子宫内膜增殖症及非典型增生各30例，子宫内膜癌90例；对照组30例，其中包括增生期及分泌期子宫内膜各15例，观察Ki67抗原在不同内膜病变及正常内膜中的阳性表达率。结果：Ki67抗原在分泌期内膜中几乎没有表达，在增生期内膜中有弱表达；在增殖症及非典型增生中有表达，但与对照组比较，无统计学意义（P〉0．05），且两者之间比较，亦无统计学意义（P〉0．05）；在子宫内膜癌组织中表达明显增高，显著高于良性病变组和对照组（P〈0．01）。而且Ki67抗原的阳性率随着临床分期及细胞分化级别的升高及淋巴转移的存在而增加。结论：Ki67抗原与子宫内膜癌发生密切相关．抗原过度表达提示子宫内膜癌患者预后不良。     

PTEN及p27在子宫内膜腺癌中的表达及临床意义

目的　研究 PTEN及 p2 7蛋白在子宫内膜腺癌中的表达及临床意义。方法　应用免疫组化法检测 11例正常增生期内膜、4 4例子宫内膜增生症及 5 2例子宫内膜腺癌 PTEN及 p2 7蛋白表达。结果　 PTEN及 p2 7蛋白在正常增生期内膜、子宫内膜简单型 /复杂型增生过长 (无不典型增生 )、子宫内膜不典型增生过长及子宫内膜腺癌中表达率分别为 10 0 .0 %、91.4 %、6 6 .7%、6 7.3%和 90 .9%、88.6 %、6 6 .7%、5 9.6 %。子宫内膜腺癌 PTEN及 p2 7蛋白表达率明显低于正常增生期内膜和简单型 /复杂型增生过长 ( P<0 .0 1) ,与不典型增生过长相比差异无显著性( P>0 .0 5 )。 PTEN及 p2 7蛋白表达随组织分化越差呈递减趋势 ,PTEN表达与子宫内膜腺癌差分化相关 ( P<0 .0 5 ) ,与其它临床病理因素无关。在子宫内膜腺癌中 PTEN及 p2 7蛋白表达有相关性 ( P=0 .0 19)。结论　 PTEN及 p2 7在子宫内膜腺癌发生、发展中起重要作用 ,并可能是子宫内膜腺癌发生中的早期事件 ,检测 PTEN及 p2 7蛋白表达有助于子宫内膜腺癌的早期诊断及预后判断     

Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression

BACKGROUND: To examine the steroid hormone dependent growth mechanism of human endometrial hyperplasia and carcinoma, expression levels of steroid receptor cofactors, such as coactivators (steroid receptor coactivator 1 [SRC-1] and p300/cyclic AMP-response element-binding protein (p300/CBP]) and corepressors (nuclear receptor corepressor [NCoR] and silencing mediator for retinoid and thyroid-hormone receptors [SMRT]), were investigated. METHODS: The expression levels of cofactors were examined immunohistochemically using 20 samples of normal endometria, 36 samples of hyperplastic endometria, and 58 of malignant endometria and were compared with the expression levels of estrogen receptor (ER), progesterone receptor (PR), and a proliferation marker, Ki-67. RESULTS: In samples of normal endometria, the expression of coactivators was observed diffusely in glandular cells in the proliferative phase, with a mean positivity index (PI) of 81.8 for SRC-1 and 91.3 for p300/CBP, whereas expression levels decreased in endometrial hyperplasia (PI: SRC-1, 58.9; p300/CBP, 83.8) and endometrial carcinoma (PI: SRC-1, 45.0; p300/CBP, 55.4). In endometrial hyperplasia, there was a significant correlation between the expression of ER and SRC-1 or p300/CBP. In contrast, there were no significant statistical or topologic correlations between the expression of coactivators and the expression of ER/PR in endometrial carcinoma. The expression of corepressors generally was limited, except for elevated expression of NCoR in endometrial hyperplasia (PI, 23.8). CONCLUSIONS: The current study showed that expression levels of the steroid receptor coactivators SRC-1 and p300/CBP were reduced in endometrial carcinoma compared with normal and hyperplastic endometrium. In addition, topologic coexpression of both coactivators and ER/PR was lost in endometrial carcinoma. Accordingly, limited response to sex steroids in patients with endometrial carcinoma may be ascribed to the dissociation of cofactors and ER/PR.