子宫内膜癌标志物表达及其临床意义研究

目的探讨p53、磷酸酶与张力蛋白同源物(PTEN)、p16、人类表皮生长因子受体-2(HER-2)、Ki67的表达及其与子宫内膜癌发生发展的相关性。方法采用免疫组织化学法检测上海市普陀区妇婴保健院病理科2009月1年至2015年12月确诊的50例正常子宫内膜组织、20例不典型增生子宫内膜组织及75例子宫内膜癌中p53、PTEN、p16、HER-2及Ki67的表达,并对不同子宫内膜组织的表达结果进行比较。结果 p53、PTEN、p16、HER-2和Ki67在正常子宫内膜和子宫内膜癌中的表达差异均有统计学意义(P0.05),在不典型增生子宫内膜中HER-2和Ki67表达显著高于正常子宫内膜(P0.05),子宫内膜癌与不典型增生子宫内膜中PTEN、Ki67的表达差异有统计学意义(P0.05)。在Ⅰ型和Ⅱ型子宫内膜癌之间p53、PTEN、p16、HER-2表达差异有统计学意义(P0.05),Ki67在Ⅰ型和Ⅱ型子宫内膜癌间表达相近(P0.05)。p53在子宫内膜癌的表达率与肿瘤的分化程度、浸润深度、脉管情况及临床分期密切相关(P0.05),而PTEN、p16、HER-2和Ki67的表达与这些临床病理特征无关(P0.05)。结论 p53、PTEN、p16、HER-2和Ki67蛋白的表达与子宫内膜癌的发生发展相关,在实际临床工作中可用于子宫内膜病变的病理诊断。     

细胞凋亡调控蛋白bcl-2和bax在多囊卵巢综合征患者子宫内膜中的表达

目的探讨多囊卵巢综合征（PCOS）患者子宫内膜中细胞凋亡调控蛋白bcl-2和bax的表达及其在PCOS患者子宫内膜病变中的意义。方法应用免疫组织化学SP方法,测定18例PCOS患者子宫内膜和27例月经周期正常、因输卵管不通或男性不育就诊的对照者子宫内膜（10例增殖期、17例分泌期）bcl-2和bax蛋白的表达。结果PCOS患者子宫内膜bcl-2表达较对照者增殖期和分泌期高（P＜0．05和P＜0．01）,但bax表达相似（p＞0．05）。结论PCOS患者子宫内膜bcl-2蛋白表达增高,与bax形成更多的异源二聚体,从而抑制PCOS子宫内膜凋亡,对其子宫内膜的异常增生改变起一定作用。     

功能失调性子宫出血和细胞凋亡,bcl-2及bax基因表达的关系

目的研究功能失调性子宫出血与细胞凋亡及其相关基因表达产物的关系。方法应用TUNEL技术检测30例正常月经周期的增生期子宫内膜，28例简单增生，2例复杂增生子宫内膜标本的凋亡指数（AI）。应用免疫组化方法检测bcl-2及bax基因在子宫内膜的表达。结果简单增生和复杂增生子宫内膜AI比正常增生期AI高（P＜0．05）；bcl-2基因在正常增生期表达比在简单增生和复杂增生表达略高，差异无显著性（P＞0．05）；bax基因在简单增生和复杂增生表达比在正常增生期表达高（P＜0．05）。结论功能失调性子宫出血的发病与细胞凋亡有关，且与bcl-2，bax表达相关。     

子宫内膜癌组织中基因及分子标志物表达及其与预后的相关性研究

目的探讨子宫内膜癌组织中雌激素受体(ER)、孕激素受体(PR)、p53抑癌基因(p53)、抗原Ki-67(Ki-67)的表达及与临床预后之间的关系。方法选取2009—2014年广州医科大学附属第一医院妇科收治的79例子宫内膜癌患者的癌组织标本,采用免疫组化法检测其中ER、PR、p53、Ki-67的蛋白表达情况。结果 79例子宫内膜癌病例中,ER、PR、p53、Ki-67阳性表达率:87.3%、88.6%、84.8%、79.7%;ER的蛋白表达与患者预后有关;PR与病理类型、肌层浸润、组织分化有关;p53与组织分化有关;Ki-67与临床分期、淋巴转移有关(均P0.05)。ER与PR的表达、p53与Ki-67的表达均呈正相关(P0.05)。结论 ER、PR、p53、Ki-67的联合检测可能作为子宫内膜癌发生、发展及临床转移的生物学指标及作为判断子宫内膜癌恶性程度及评估预后的分子标志物,其具体作用机制值得进一步研究。     

细胞核增殖相关抗原ki67和bcl-2、bax与恶性卵巢上皮性肿瘤临床病理及预后的关系

目的研究细胞核增殖相关抗原ki67和凋亡抑制基因bcl-2 、促凋亡基因bax与恶性卵巢上皮性肿瘤临床病理及预后的关系.方法采用免疫组化SP法检测85例卵巢上皮性肿瘤中ki67、bcl-2、bax表达情况.结果①ki67指数在恶性卵巢上皮性肿瘤中显著高于良性及交界性肿瘤;与恶性卵巢上皮性肿瘤组织学分级呈正相关,与预后呈负相关.②bax表达水平在卵巢恶性肿瘤组中高于良性组,与恶性卵巢上皮性肿瘤组织学分级呈负相关,与预后呈正相关;bcl-2表达水平在恶性组中高于良性组及交界组;高分化组中bcl-2∶bax≤1的患者所占比例高于中、低分化组,bcl-2∶bax≤1患者预后较好.③恶性卵巢上皮性肿瘤中ki67指数与bax表达负相关,与bcl-2表达及bcl-2∶bax比值正相关;低增殖高凋亡易感组预后好于高增殖低凋亡易感组.④临床分期和bax表达水平是影响恶性卵巢上皮性肿瘤患者预后的主要因素.结论ki67可作为评价卵巢肿瘤生物学行为及预后的指标,bcl-2、bax相互作用,对恶性卵巢上皮性肿瘤的发生、发展及预后中起一定作用,高增殖低凋亡易感性促使肿瘤恶性发展,bax为恶性卵巢上皮性肿瘤患者的保护因素.     

microRNA-145对卵巢癌SKOV3细胞抑癌基因p53表达调控研究

目的 探讨microRNA -145（miR-145）对卵巢癌SKOV3细胞抑癌基因p53表达的调控。 方法 选取2012年2月至2013年4月在重庆医科大学,通过慢病毒转染技术将含miR-145的质粒转入SKOV3细胞中,经嘌呤霉素筛选建立稳定表达miR-145的SKOV3细胞株。实时定量荧光RT-PCR验证miR-145的表达情况,western-blot检测过表达miR-145后SKOV3细胞中p53蛋白表达量的变化。 结果　过表达miR-145的SKOV3细胞p53蛋白相对表达量实验组0.714±0.18,对照组0.333±0.07,增高1.14倍（P＜0.05）。 结论　miR-145可能通过增强卵巢癌SKOV3细胞中抑癌基因p53的表达来降低细胞的肿瘤恶性程度。     

子宫内膜癌标志物表达及其临床意义研究北大核心CSCD

目的探讨p53、磷酸酶与张力蛋白同源物(PTEN)、p16、人类表皮生长因子受体-2(HER-2)、Ki67的表达及其与子宫内膜癌发生发展的相关性。方法采用免疫组织化学法检测上海市普陀区妇婴保健院病理科2009月1年至2015年12月确诊的50例正常子宫内膜组织、20例不典型增生子宫内膜组织及75例子宫内膜癌中p53、PTEN、p16、HER-2及Ki67的表达,并对不同子宫内膜组织的表达结果进行比较。结果 p53、PTEN、p16、HER-2和Ki67在正常子宫内膜和子宫内膜癌中的表达差异均有统计学意义(P<0.05),在不典型增生子宫内膜中HER-2和Ki67表达显著高于正常子宫内膜(P<0.05),子宫内膜癌与不典型增生子宫内膜中PTEN、Ki67的表达差异有统计学意义(P<0.05)。在Ⅰ型和Ⅱ型子宫内膜癌之间p53、PTEN、p16、HER-2表达差异有统计学意义(P<0.05),Ki67在Ⅰ型和Ⅱ型子宫内膜癌间表达相近(P>0.05)。p53在子宫内膜癌的表达率与肿瘤的分化程度、浸润深度、脉管情况及临床分期密切相关(P<0.05),而PTEN、p16、HER-2和Ki67的表达与这些临床病理特征无关(P>0.05)。结论 p53、PTEN、p16、HER-2和Ki67蛋白的表达与子宫内膜癌的发生发展相关,在实际临床工作中可用于子宫内膜病变的病理诊断。     

p27kip1和ki-67在子宫内膜异位症中的表达与意义

目的 通过观察p27^kip1、ki-67的表达探讨子宫内膜细胞增殖能力对子宫内膜异位症发病的影响。方法 应用免疫组化SP法检测36例子宫内膜异位症患者（EMs组）的异位和在位内膜及23例正常子宫内膜中p27^kip1、ki-67的表达情况。结果①异位内膜p27^kip1腺体胞质表达率较正常子宫内膜明显增强（P〈0．05）；异位内膜p27^kip1腺体胞核表达率较正常子宫内膜明显下降（P〈0．05）。②正常子宫内膜与在位内膜腺体ki-67表达增生期显著高于分泌期（P〈0．05）；异位内膜ki-67表达无周期性变化；异位内膜ki-67分泌期增殖指数显著高于在位内膜（P〈0．01）。③EMs组异位内膜p27^kip1与ki-67表达呈负相关（P〈0、05）。结论ki-67增殖指数反映了子宫内膜细胞的增殖活性，异位内膜细胞增殖活跃，而p27^kip1表达下降，负性调节细胞增殖能力下调，p27^kip1和ki-67可能在子宫内膜异位症发生发展中起重要作用。     

黄体功能不全患者月经期子宫内膜细胞凋亡的研究

目的：探讨黄体功能不全（luteal phase defect LPD)患者月经期子宫内膜细胞的凋亡及意义。方法：应用免疫组织化学S－P方法,测定35例黄体功能不全患者和19例对照组月经期子宫内膜bcl-2和bax蛋白的表达,同时应用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法（TUNEL）测定二组月经期子宫内膜的细胞凋亡。结果：LPD组患者子宫内膜bcl-2表达较对照组高（P＜0．01）,而bax表达较对照组（P＜0．05）,凋亡指数（apoptotic index AI）对照组高于LPD组（P＜0．01）,且随着bcl-2的表达强度增加而减少（Ｐ＜０．０１）,而随着bax的表达强度增加而增加（P＜0．01）,结论：LPD组患者月经期子宫内膜 bcl-2表达增高bax表达降低,从而抑制LPD患者子宫内膜细胞凋亡,对其子宫内膜的异常变改变起一定作用。     

miR-26a-5p通过靶向THAP2促进子宫内膜癌细胞凋亡

目的:研究miR-26a-5p靶向THAP2对子宫内膜癌细胞凋亡的影响。方法:实时荧光定量RT-PCR法检测子宫内膜癌细胞中miR-26a-5p表达水平。构建以慢病毒为载体的miR-26a-5p过表达和干扰质粒,分别转染子宫内膜癌细胞系Ishikawa与KLE,实时荧光定量RT-PCR法检测miR-26a-5p及下游分子THAP2转录水平。流式细胞技术分析miR-26a-5p表达对子宫内膜癌细胞凋亡的影响。结果:子宫内膜癌细胞Ishikawa与KLE均表达miR-26a-5p;miR-26a-5p过表达能增加THAP2的转录水平,促进子宫内膜癌细胞凋亡;miR-26a-5p下调能抑制THAP2的转录水平,抑制子宫内膜癌细胞凋亡。结论:miR-26a-5p可提高THAP2的转录水平,促进子宫内膜癌细胞凋亡,明确这种调控机制可能为子宫内膜癌预防诊断和治疗带来新的契机。     

子宫与卵巢异位内膜细胞凋亡和增殖特性的研究

目的　探讨子宫腺肌病与卵巢异位囊肿异位内膜的细胞凋亡和增殖特性及发病机制。方法　 2 0 0 2年 6月至 2 0 0 3年 6月南方医科大学珠江医院采用免疫组化S P法 ,检测子宫腺肌病 (46例 )和卵巢异位囊肿 (6 0例 )的在位及异位子宫内膜中凋亡调控基因蛋白bcl 2、bax及细胞增殖标记物Ki 6 7蛋白的表达。结果　bcl 2蛋白、bax蛋白及Ki 6 7蛋白在两症的在位内膜以及子宫腺肌病异位内膜中均呈现周期性改变 ,而bcl 2蛋白及Ki 6 7蛋白在卵巢异位囊肿异位内膜中呈持续性增强 ,较在位内膜差异有显著性意义 (P <0 0 5 )。结论　子宫腺肌病异位内膜的细胞凋亡和增殖受卵巢性激素周期性的调节 ,卵巢异位囊肿异位内膜则相反 ,两者细胞凋亡和增殖特性有着明显的不同 ,是两种不同的疾病。     

Effect of menstrual cycle and hormonal treatment on ki-67 and bcl-2 expression and adenomyosis.

OBJECTIVE: To study the expression of proliferation markers (ki-67) and anti-apoptotic protein (bcl-2) in adenomyotic lesions during the menstrual cycle or following the use of steroid hormones. PATIENTS AND METHODS: Ninety patients of reproductive age were included, who were submitted to endometrial resection for treatment of adenomyosis-related menorrhagia. Seven patients were using oral contraceptives and another seven had a levonorgestrel intrauterine device (IUD) (Mirena) in the uterine cavity at the time of the hysteroscopic procedure. Untreated patients were divided into four groups: menstruation/early proliferative phase (n = 24), late proliferative (n = 19), early luteal phase (n = 7) and late luteal phase (n?=?26). Bcl-2 and ki-67 expression was determined in paraffin-embedded tissue blocks using immunohistochemical methods. RESULTS: Proliferation rates in adenomyotic lesions increased during the proliferative phase, reaching a peak during ovulation to decrease to values close to zero in the late luteal phase. Bcl-2 expression showed a similar curve with peak values during the later proliferative phase followed by a significant decrease in the number of cases showing strong positive expression in the late luteal phase. Both Mirena and oral contraceptives decreased ki-67 expression on adenomyosis but only Mirena was affective in diminishing bcl-2 expression. CONCLUSION: During the luteal phase, both ki-67 and bcl-2 expression is reduced in adenomyotic lesions in a similar way to that occurring in patients using Mirena. Oral contraceptives, on the other hand, do not affect bcl-2 expression in adenomyosis.     

妊娠肝内胆汁淤积症患者胎盘细胞凋亡及调控基因的研究

目的　通过观察妊娠肝内胆汁淤积症 (ICP)患者胎盘细胞凋亡调控基因p5 3、bax和bcl 2在胎盘中的表达 ,探讨细胞凋亡基因在胎盘细胞凋亡中的作用。方法　采用原位末端标记法(TUNEL)和免疫组织化学方法对 3 1例ICP患者 (ICP组 )的胎盘组织中p5 3、bax和bcl 2基因表达及调亡指数进行检测 ,并以 3 1例正常妊娠妇女的胎盘组织作对照 (对照组 )。结果　 (1)ICP组胎盘组织中细胞滋养细胞、合体滋养细胞、蜕膜细胞及间质细胞中细胞凋亡指数分别为 (49 1± 9 1) %、(46 6±9 8) %、(3 5 1± 9 5 ) %、(3 8 7± 9 7) % ,明显高于对照组的 (2 2 5± 6 2 ) %、(2 1 6± 5 2 ) %、(17 9±6 2 ) %、(17 0± 4 7) %。两组比较 ,差异有极显著性 (P <0 0 1)。 (2 )而调控基因p5 3的表达 ,ICP组明显高于对照组 ,两组比较 ,差异有极显著性 (P <0 0 1) ;bax的表达在两组滋养细胞中比较 ,差异无显著性 (P >0 0 5 )。但在合体滋养细胞、蜕膜细胞及间质细胞中 ,ICP组明显高于对照组 ,两组比较 ,差异有极显著性 (P <0 0 1) ;bcl 2的表达在ICP组胎盘组织细胞滋养细胞、合体滋养细胞、蜕膜细胞及间质细胞中 ,均明显低于对照组 (P <0 0 1)。 (3 )p5 3、bax和bcl 2在ICP组合体滋养细胞中的表达分别是 (75 9± 8 2 ) %、(65     

Effect of menstrual cycle and hormonal treatment on ki-67 and bcl-2 expression and adenomyosis

Objective.?To study the expression of proliferation markers (ki-67) and anti-apoptotic protein (bcl-2) in adenomyotic lesions during the menstrual cycle or following the use of steroid hormones.

Patients and methods.?Ninety patients of reproductive age were included, who were submitted to endometrial resection for treatment of adenomyosis-related menorrhagia. Seven patients were using oral contraceptives and another seven had a levonorgestrel intrauterine device (IUD) (Mirena^®) in the uterine cavity at the time of the hysteroscopic procedure. Untreated patients were divided into four groups: menstruation/early proliferative phase (n?=?24), late proliferative (n?=?19), early luteal phase (n?=?7) and late luteal phase (n?=?26). Bcl-2 and ki-67 expression was determined in paraffin-embedded tissue blocks using immunohistochemical methods.

Results.?Proliferation rates in adenomyotic lesions increased during the proliferative phase, reaching a peak during ovulation to decrease to values close to zero in the late luteal phase. Bcl-2 expression showed a similar curve with peak values during the later proliferative phase followed by a significant decrease in the number of cases showing strong positive expression in the late luteal phase. Both Mirena and oral contraceptives decreased ki-67 expression on adenomyosis but only Mirena was affective in diminishing bcl-2 expression.

Conclusion.?During the luteal phase, both ki-67 and bcl-2 expression is reduced in adenomyotic lesions in a similar way to that occurring in patients using Mirena. Oral contraceptives, on the other hand, do not affect bcl-2 expression in adenomyosis.     

Bax,Bcl-2, and p53 expression in endometrial cancer

BACKGROUND: It has not been fully clarified whether alteration of Bax and other apoptosis-relating proteins of Bcl-2 and p53 is involved in endometrial carcinogenesis. METHODS: A total of 56 frozen tissues, which included 14 normal endometria, 13 endometrial hyperplasias (10 without atypia and 3 with atypia), and 29 endometrial carcinomas, were examined for the expression of Bax, Bcl-2, and p53 using immunohistochemistry. For Bax-negative cases, PCR-direct sequencing was performed for the bax gene. For cases with p53 overexpression, mutational analysis was performed for the p53 gene using a yeast functional assay and sequencing. RESULTS: Both Bax and Bcl-2 were distinctly expressed in the normal proliferative phase endometrium. A decreased Bcl-2/Bax ratio in the secretory phase endometrial gland cells due to suppressed Bcl-2 expression was observed. Bax expression was positive in all 13 endometrial hyperplasias, while it was absent in 6 of 29 endometrial carcinomas (20.7%). Negative Bax expression in endometrial carcinoma was not related to tumor stage, histologic subtype, or other histopathologic prognostic factors. Bax expression showed no relationship to either p53 overexpression or Bcl-2 expression. In the DNA of 6 Bax-negative cases, we found a frameshift insertion mutation at codon 58 (AAG to CAAG) in the BH3 domain despite the absence of mutation in the (G)8 tract, suggesting that this codon may be another preferred target for bax mutation other than the (G)8 tract. Mutational analysis was available for 7 of 10 cases with p53 overexpression, in which 5 cases were found to have a missense mutation and 2 cases had no mutation of the p53 gene. At least 10 of 29 (34.5%) cases of endometrial carcinoma were associated with sequence-verified mutation in the bax gene and/or p53 gene. CONCLUSIONS: The bax gene frameshift mutation appears to cause a loss of Bax expression in endometrial carcinoma. Codon 58 may be a preferred target of bax gene mutation in endometrial carcinomas. The bax gene mutation seems to occur in the early stage of the genesis of a subset of endometrial carcinomas.     

The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer.

OBJECTIVE: The present study was designed to analyse the relationship between apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53, proliferation markers (PCNA and mitotic index), human papillomavirus (HPV) and angiogenesis in cervical cancer and their impact on clinical outcome. STUDY DESIGN: Tumours from 111 patients were assessed by immunohistochemistry for the expression of bcl-2, bax, p53 and PCNA, by PCR for the presence of HPV-DNA, for the quantification of the mitotic index and the microvessel density (CD 31). The results were correlated with various histopathologic characteristics and survival. RESULTS: The multiple Cox's regression analysis for overall survival of all prognostic variables gave as best model: bcl-2 (P<0.001), lymphovascular permeation (P=0.004), mitotic index (P=0.019), tumour grade (P=0.048) and FIGO stage (P=0.070). Subanalysis was performed for the patients where the lymph node status was known (n=79). Adding the lymph node status gave as best model for overall survival bcl-2 (P=0.001), lymphovascular permeation (P=0.003) and mitotic index (P=0.044). However, they hardly influenced the association. CONCLUSION: In the apoptotic pathway of cervical cancer, bcl-2 is one of most important proteins. It can probably not only mediate cell death but also regulate cell growth. A better understanding of their relations will probably provide the basis for more rational cancer therapies in the future.     

Programmed cell death (apoptosis) as a possible pathway to metalloproteinase activation and fetal membrane degradation in premature rupture of membranes

OBJECTIVE: Increased matrix metalloproteinase 2 expression and activity are associated with premature rupture of fetal membranes. A proapoptotic protein produced in response to deoxyribonucleic acid fragmentation, p53, can bind to the matrix metalloproteinase 2 gene promoter and cause increased gene expression. It promotes apoptosis by inducing the expression of the proapoptotic bax gene and inhibiting the antiapoptotic bcl-2 gene. This study was undertaken to investigate the expression pattern of apoptotic elements in pregnancy complications that may cause increased expression of the gene for matrix metalloproteinase 2. STUDY DESIGN: Amniochorial membranes were collected from the following groups of women: (1) women with premature rupture of fetal membranes, (2) women with preterm labor and intact membranes, and (3) women with term labor after vaginal delivery. Deoxyribonucleic acid fragmentation was tested with ligation-mediated polymerase chain reaction and the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyribonucleoside triphosphate end-labeling assay. Matrix metalloproteinase 2, p53, bcl-2, and bax gene expression patterns were studied with quantitative competitive polymerase chain reaction. Statistical analysis was performed with the Tukey-Kramer multiple comparison test. RESULTS: Quantitative competitive polymerase chain reaction documented a 10-fold increase in the expression of the gene for matrix metalloproteinase 2 in premature rupture of fetal membranes with respect to term and preterm labor. This induction coincided with an increase in the expressions of the proapoptotic genes p53 and bax and a drop in the expression of the antiapoptotic gene bcl-2. Ligation-mediated polymerase chain reaction revealed deoxyribonucleic acid fragmentation in specimens from premature rupture of fetal membranes and not in those from preterm labor or labor at term. Histochemical analysis documented fragmented deoxyribonucleic acid in chorionic and amniotic cells. CONCLUSION: This study suggests that apoptosis is associated with premature rupture of fetal membranes. Deoxyribonucleic acid fragmentation, associated with elevations in the levels of the two proapoptotic gene products evaluated (p53 and bax ) and a drop in the level of the antiapoptotic bcl-2, was seen in premature rupture of the fetal membranes. Induction of matrix metalloproteinase 2 may be a function of p53 gene expression increase in premature rupture of fetal membranes.     

大剂量米非司酮和孕激素联合应用治疗子宫内膜癌的临床研究

目的　研究大剂量米非司酮、大剂量孕激素以及二者联合应用对子宫内膜癌患者的治疗效果 ,并探讨其作用机制。方法　将 3 0例经诊刮确诊的子宫内膜癌患者随机分为 3组 ,每组 10例 ,术前用药 5d。米非司酮组术前用米非司酮 ( 10 0mg d) ,醋酸甲羟孕酮组术前用醋酸甲羟孕酮 ( 50 0mg d) ,联合组术前用米非司酮 ( 10 0mg d)、醋酸甲羟孕酮 ( 50 0mg d)。各组用药前后行自身对照 ,观察癌细胞组织形态学改变及雌激素受体 (ER)、孕激素受体 (PR)、增殖细胞核抗原 (PCNA)、凋亡相关基因 (bcl 2、bax)及CD44 v6基因表达的变化。结果　各组治疗后 ,癌细胞分化均趋向成熟 ,分泌活跃 ,可在癌组织中观察到凋亡的癌细胞 ,联合组治疗后变化最明显。醋酸甲羟孕酮组治疗前后 ,免疫组织化学 (免疫组化 )评分分别为PR( 2 9± 1 1、1 6± 0 8)、ER( 2 8± 0 9、1 4± 0 9)、PCNA( 0 84± 0 11、0 60±0 12 )、bcl 2 ( 0 2 3 6± 0 0 89、0 157± 0 981)和CD44 v6( 4 6± 1 8、2 5± 1 9) ,表达均降低 (所有P <0 0 1) ,bax( 0 2 0± 0 10、0 42± 0 0 7)表达增多 (P <0 0 1)。米非司酮组治疗前后免疫组化评分分别为PR( 3 4± 1 0、1 9± 0 8)、ER( 2 7± 0 9、1 2± 0 7)、PCNA( 0 80± 0 15、0     

The patterns of expression of an apoptosis-related CK18 neoepitope, the bcl-2 proto-oncogene, and the Ki67 proliferation marker in normal, hyperplastic, and malignant endometrium.

Expression of a neoepitope on cytokeratin 18, recognized by the monoclonal antibody M30, is an early indicator of apoptosis in epithelial cells. The aim of this study was to determine the equilibrium between apoptosis (M30), anti-apoptosis (bcl-2), and proliferation (Ki-67) in different endometrial conditions. Paraffin-embedded samples (n = 107), representing proliferative endometrium (18), secretory endometrium (19), postmenopausal endometrium (15), disordered proliferative endometrium (6), simple hyperplasia (12), complex hyperplasia (8), and endometrial adenocarcinoma (29), were evaluated immunohistochemically. The indirect streptavidin-biotin-horseradish peroxidase technique, with 3-amino-9-ethylcarbazole as the chromogen, was used to visualize the reactions. Proliferative endometrium showed high bcl-2 and Ki-67 expression levels with no M30. In the secretory phase, the balance was tipped in favor of M30 with a decrease of bcl-2 and Ki-67. Postmenopausal endometrium revealed high Ki-67 and bcl-2 expression levels and no M30. In complex hyperplasia, M30, bcl-2, and Ki-67 showed increased expression. In endometrial carcinoma, an increasing reactivity for M30 and Ki-67 was seen as the grade progressed. bcl-2 reacted weakly and only in grade 1 cancer. Immunohistochemistry facilitates the study of the expression of proteins related to cyclic endometrial activity. Interruption of these cyclic events is associated with specific disturbances in the expression patterns of these proteins.     

Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium.

OBJECTIVE: The aim of this study was to determine whether immunohistochemical analysis of molecular parameters can provide an alternative method for classification of endometrial cancer cases according to their aggressiveness. METHODS: Sixty-four cases of endometrial carcinoma were assigned to three groups: group I--28 cases of endometrioid well and moderately differentiated (G1-G2) carcinoma; group II--14 cases of endometrioid poorly differentiated (G3) carcinoma; group III--22 cases of serous papillary endometrial cancer. Immunohistochemistry was used to determine the existence of estrogen receptors (ER), progesterone receptors (PR), and the expression of bcl-2, p53, HER-2/neu and Ki-67. RESULTS: There was a significant difference in the immunohistochemical profile of the studied molecular parameters comparing the three study groups. The endometrioid G1-G2 cases (group I) were characterized by increased immunoreactivity for ER and PR (85.7% and 78.6%, respectively), increased immunoreactivity for bcl-2 (42.8%) and low expression of p53 (14.3%) and HER-2/neu (14.3%). In contrast to group I cases, the serous papillary endometrial cancer cases (group III) were characterized by immunonegativity for ER, PR and bcl-2 and high immunoreactivity for p53 (81.8%) and HER-2/neu (45.4%). The endometrioid G3 cases (group II) demonstrated an intermediate immunoprofile, characterized by immunonegativity for ER, PR and HER-2/neu, low immunoreactivity for bcl-2 (7.1%) and high expression of p53 (57.1%). The expression of Ki-67 did not differ significantly comparing the different cases of endometrial cancer. CONCLUSION: This study provides evidence that the immunohistochemical analysis of endometrial carcinoma differentiates between different grades and histological types, thus being useful in the distinction of high risk cases.