p53、bcl-2和bax基因表达与IUGR胎盘细胞凋亡的相关性研究

目的：研究胎儿宫内发育迟缓（ｉｎｔｒａｕｔｅｒｉｎｅ　ｇｒｏｗｔｈ　ｒｅｔａｒｄａｔｉｏｎ,ＩＵＧＲ)患者的胎盘细胞凋亡,以ｐ５３、ｂｃｌ－２和ｂａｘ相关性。方法：收集ＩＵＧＲ ２０份和正常足月分娩１２例的胎盘组织,应用原位末端标记(TUNEL)法检测其胎盘组织中的细胞凋亡,免疫组化法（ＩＨＣＡ）检测胎盘组织中ｐ５３、ｂｃｌ－２和ｂａｘ基因表达。结果：①正常和ＩＵＧＲ胎盘组织中均可见凋亡细胞,但ＩＵＧＲ胎盘中细胞凋亡指数（ａｐｏｐｔｏｓｉｓ　ｉｎｄｅｘ,ＡＩ）为１６．７～６８．３１,明显高于正常胎盘中的９．２～３０．４／高倍视野（平均２０．６７／高倍视野）,差异有显著性（Ｐ＜０．０５）;②ＩＵＧＲ ２０例胎盘组织中均有ｂａｘ过表达（４０％～９０％),高于正常组织（１０％～４０％）,差异有显著性（Ｐ＜０．０５）;③正常及ＩＵＧＲ胎盘组织中均未见ｂｃｌ－２表达;④ｐ５３在ＩＵＧＲ胎盘组织中的表达为５０％～８０％,而在正常组织中为５５％～８０％（Ｐ＞０．０５）;⑤ＩＵＧＲ２０例胎盘组织中细胞ＡＩ与ｂａｘ的表达呈正相关,与ｐ５３表达无关,ｂａｘ与ｐ５３之间无相关性。结论：①正常孕妇和ＩＵＧＲ患者胎盘组织中均有细胞凋亡,但ＩＵＧ     

凋亡相关基因bcl-2和bax在妇科肿瘤中的研究进展

bcl-2和bax基因是研究较多的两种凋亡相关基因.近年发现,各种妇科肿瘤组织中均有bcl-2、bax基因蛋白表达,且两者在肿瘤的发生、发展中起重要作用,并可作为妇科肿瘤的有效的预后指标,但其作用机制尚待进一步深入研究,以期为妇科肿瘤提供一种合理有效的基因治疗手段.     

宫颈癌组织中HPV、EBV、p53、bcl-2基因产物表达及临床病理意义

目的 :探讨人乳头瘤病毒 (HPV)、EB病毒 (EBV)和p5 3、抗细胞凋亡因子 (bcl- 2 )基因产物在宫颈癌中的表达及临床意义。方法 :对 2 0例正常宫颈组织标本及 5 0例宫颈癌标本石蜡包埋制成切片 ,采用免疫组织化学染色方法(LSAB)检测HPV、EBV产物和p5 3、bcl 2、基因产物表达。结果 :在宫颈癌组织中HPV、EBV的阳性表达率为 4 4 %、5 2 % ,明显高于正常宫颈组织的 5 %、10 % (P <0 .0 5 ) ,HPV和EBV的混合感染率为 18% (9/ 5 0 )。p5 3基因产物阳性表达率宫颈癌组 (2 4 % )高于正常宫颈组织 (0 % ) (P <0 .0 5 )。在宫颈癌组织中bcl 2基因产物的阳性表达率 (72 % )明显高于正常宫颈组织的 (2 0 % ) (P <0 .0 5 )。HPV与p5 3有相关性 ,EBV与bcl 2相关。结论 :①HPV、EBV在宫颈癌组织中的感染率明显高于正常人。②HPV可能通过造成p5 3基因产生突变而失活 ,导致宫颈癌的发生 ;EBV可能通过使bcl 2基因蛋白产生上调性表达 ,抑制细胞凋亡 ,导致宫颈细胞癌变     

癌基因bcl—2及抑癌基因p53在子宫内膜癌的表达及临床 …

目的：研究癌基因ｂｃｌ－２及抑癌基因ｐ５３在子宫内膜癌发生，发展中的作用，方法：采用免疫组化ＡＢＣ法检测４９例子宫内膜癌中ｂｃｌ－２ｐ５３基因蛋白的表达，结果：４９例子宫内膜癌中的２６例ｂｃｌ－２表达阳性，占５３％１２例ｐ５３表达阳性，占２５％，子宫内膜组织学分级Ｇ１，Ｇ２，ｂｃｌ－２表达率（６６％）显著高于Ｇ３表达率（２１％，Ｐ〈０．０５），而Ｇ３ｐ５３表达率（４６％）显著高于Ｇ１，Ｇ２表达率（     

分析p16、p53及Ki-67在宫颈癌患者中的表达及联合检测的诊断价值

目的 探讨p16、p53及Ki-67在宫颈癌患者中的表达意义及三项指标联合检测的诊断效能。方法 选取2019年6月至2022年10月在桂林医学院附属医院就医并确诊为宫颈癌的140例患者纳入宫颈癌组,另选取60例经本院确诊的高级别鳞状上皮病变患者纳入宫颈上皮内病变组,均为CIN2。收集本研究纳入患者的病理组织标本并检测p16、p53及Ki-67阳性表达情况,明确p16、p53及Ki-67与宫颈癌患者病理特征的关系,分析p16、p53及Ki-67三项指标联合检测对宫颈癌的诊断价值。结果 宫颈癌组病理组织标本中p16、p53及Ki-67阳性表达率均明显高于宫颈上皮内病变组（均P <0.05）;宫颈癌组中不同年龄患者的p16、p53及Ki-67阳性表达对比差异均无统计学意义（P>0.05）,不同FIGO分期及淋巴结转移患者p16、p53及Ki-67阳性表达明显升高（均P <0.05）;p16、p53、Ki-67三项联合的诊断效能包括灵敏度、特异度、阳性预测值、阴性预测值均明显高于单一指标的检测效能。结论 宫颈癌组织中p16、p53、Ki-67蛋白的阳性表达与宫颈癌患者病情的发...     

凋亡调节基因bcl-2/bax与卵巢早衰的关系

细胞凋亡在生物有机体的正常生理调节和病理过程中都有十分重要作用。近来研究表明,卵巢早衰的发病机制是由于卵母细胞过快耗竭所致,卵母细胞的活化及持续生长发育依赖于其周围的颗粒细胞的营养及旁分泌作用。bcl-2/bax参与卵巢颗粒细胞的凋亡过程,细胞是走向生存还是死亡取决于bc1-2/bax的比值,间接影响卵母细胞的凋亡,bcl-2/bax在卵巢早衰的发生和发展中起重要作用。     

CEA、p16、p53、Ki-67在宫颈腺癌的表达及意义

宫颈癌大部分为鳞状细胞癌,腺癌约占5%～15%,近年资料显示有逐渐增高的趋势并有趋于年轻化的倾向,多数学者认为宫颈腺癌的预后比宫颈鳞癌差[1,2],其原因尚不清楚,但在病理诊断中宫颈腺癌漏、误诊率较高可能是原因之一.     

抗细胞凋零基因bcl-2和bax与卵巢上皮性肿瘤的关系

目的:研究抗凋零基因bcl-2和bax与卵巢上皮性肿瘤发生及预后的关系。方法:通过免疫组化方法,用抗bcl-2及抗bax抗体检测卵巢上皮肿瘤76份(良性27份、交界性24份、恶性25份)中bcl-2和bax的表达产物,并以正常卵巢12份做对照。结果:正常卵巢组织12份中bcl-2和bax阳性检出率为0,在良性、交界性及恶性肿瘤组织中bcl-2和bax的阳性检出率分别为7.4%(2/27)、16.7%(4/24)、36.0%(9/25),22.2%(6/27)、45.8%(11/24)、56.0%(14/25),良性与恶性肿瘤之间差异有显著性(P<0.05),而且bax的表达率比bcl-2高(P<0.05),bax在恶性肿瘤组Ⅰ级与Ⅲ级间差异有显著性(P<0.05)。结论:抗细胞凋零基因bcl-2和bax过度表达可能与卵巢上皮性肿瘤发生有关,推测bax不仅参与细胞凋零的调控,而且可能与肿瘤分化及预后有关。     

Fhit和ki-67在子宫内膜异位症的表达及意义

目的:通过观察脆性组氨酸三联体Fhit和细胞核增殖抗原ki-67在子宫内膜异位症的表达,探讨Fhit和ki-67在子宫内膜异位症发病中的作用。方法:用免疫组化SP法检测58例子宫内膜异位症(EMS)患者的异位内膜和在位内膜及15例子宫肌瘤患者子宫内膜(对照组)Fhit和ki-67的表达。结果:Fhit主要在腺上皮细胞的胞浆和胞膜表达,其表达强弱顺序为:对照组子宫内膜>EMS组在位内膜>EMS组异位内膜,EMS在位和异位内膜Fhit表达在增生期和分泌期无统计学差异(P>0.05);EMS组在位内膜的Fhit表达在临床r-AFS不同分期中无统计学差异(P>0.05),但异位内膜的Fhit表达在临床r-AFS不同分期中差异显著。ki-67主要在腺上皮细胞的胞核和胞膜表达,EMS在位内膜和对照组子宫内膜增生期ki-67表达均显著强于分泌期,EMS异位内膜腺体中ki-67表达在增生期和分泌期无统计学差异(P>0.05);EMS组异位内膜腺体ki-67表达在增生期弱于自身在位内膜(P<0.01),但分泌期强于其自身在位内膜(P<0.01)。EMS异位内膜腺体Ⅰ~Ⅱ期的ki-67表达高于Ⅲ、Ⅳ期,但在位内膜ki-67表达在不同临床分期中无统计学差异(P>0.05)。结论:Fhit和ki-67可能与子宫内膜异位症有关。     

p53及细胞周期素D1在子宫内膜癌中的表达及意义

目的　探讨 p5 3及细胞周期素D1(cyclinD1)在子宫内膜癌中的表达及其临床意义。方法　 1998～2 0 0 2年采用免疫组化LSAB法检测 4 2例子宫内膜癌中 p5 3、cyclinD1的表达。结果　 4 2例子宫内膜癌中 19例p5 3表达阳性 ,占 4 5 2 % ,p5 3与子宫内膜癌的细胞分级、肌层浸润深度有关 ( P<0 0 5 )。 17例子宫内膜癌cyclinD1表达阳性 ,占 4 0 5 % ,cyclinD1与子宫内膜癌的细胞分级、临床分期、淋巴结转移有关 (P <0 0 5 )。p5 3、cyclinD1协同表达 15例 ,均为晚期或低分化癌。结论　p5 3、cyclinD1作为细胞周期调节因子参与子宫内膜癌的发生、发展 ,其协同作用促进子宫内膜癌的发展、且预后不良     

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.     

Bcl-2、Bax在米非司酮治疗前后子宫内膜单纯性增生组织中的表达

目的:探讨米非司酮对子宫内膜单纯性增生的调节机制。方法:正常子宫内膜组织10例(增生期和分泌期各5例),单纯性增生子宫内膜43例,同一患者口服3个月米非司酮(10 mg/d)治疗后的子宫内膜标本43例。采用链酶菌素-生物素(S-P)免疫组化染色方法测定bcl-2、bax的表达量采用SPSS11.5统计学软件包进行数据处理,以P<0.05为有显著性差异。结果:增生期子宫内膜bcl-2阳性信号明显高于分泌期(P<0.05),单纯性增生bcl-2表达明显高于正常增生期子宫内膜(P<0.05)。与单纯性增生相比,米非司酮治疗后,子宫内膜bcl-2明显下降(P<0.05)。分泌期bax表达明显高于增生期(P<0.05),单纯性增生bax表达明显低于正常增生期子宫内膜(P<0.05)。与单纯性增生相比,米非司酮治疗后,子宫内膜bax明显增高(P<0.05)。结论:RU486增加了子宫内膜bax的表达,减少了bcl-2的表达,可能是其促进细胞凋亡,抑制子宫内膜增生的机制之一。     

Apoptosis in epithelial ovarian tumours Prognostic significance of clinical and histopathologic factors and its association with the immunohistochemical expression of apoptotic regulatory proteins (p53, bcl-2 and bax)

OBJECTIVE: The objective was to establish the importance of apoptosis-related genes and the apoptotic index (AI) as prognostic factors in patients with epithelial ovarian tumours. MATERIAL AND METHODS: Tumour specimens from 130 epithelial ovarian tumours were examined for expression of p53, bcl-2 and bax proteins. The apoptotic index was evaluated by modified terminal deoxynucleotide-transferase-mediated digoxigenin triphosphate-biotin nick end-labelling (TUNEL) methods and by haematoxylin-eosin (H-E) staining. Other clinical and histopathological variables were also analysed. Statistical analyses were performed using the SPSS 10.0 package. RESULTS: The apoptotic index detected by H-E and enzymatic assay was high in the majority of carcinomas (serous, endometrioid and clear cell (p=0.001). In the univariate survival analysis, high apoptotic index, high p53 and low bcl-2 expression, significantly correlated with shorter survival and shorter disease-free periods (p<0.01). In multivariate analysis the age (p=0.026; CI: 1.035-1.066 and p=0.011; CI: 1.835-2.077), FIGO stage (p=0.017; CI: 1.385-4.514 and p=0.024; CI: 1.217-1.940), p53 expression (p=0.03; CI: 1.017-1.627 and p=0.02; CI: 1.050-2.350) and apoptotic index (p=0.019; CI: 1.375-1.750 and p=0.019; CI: 1.442-2.085) were revealed to be independent prognostic factors for survival and recurrence, respectively. CONCLUSIONS: Our results indicate that the apoptotic index and p53 nuclear accumulation are independent predictive factors of recurrence and short survival. Our data also suggest different patterns of alterations for the various tumour types.     

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     

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.     

雌激素受体、孕激素受体、C-erbB-2和Ki-67在子宫内膜癌中的表达及其与临床病理相关性

目的 探讨雌激素受体（ER）、孕激素受体（PR）、C-erbB-2和Ki-67在不同子宫内膜组织中的表达及其与临床病理的相关性。方法 采用免疫组化S-P法检测2004年1月至2013年1月郑州人民医院病理科存档30例正常子宫内膜、30例不典型增生、80例子宫内膜癌组织中ER、PR、C-erbB-2、Ki-67的表达。结果　ER、PR在正常子宫内膜、不典型增生和子宫内膜癌中表达逐渐降低(P<0.05),在不同分化子宫内膜癌组织类型中表达有差异(P<0.05);C-erbB-2在正常子宫内膜中不表达,在不典型增生中表达为53.33%和子宫内膜癌中表达为80.00%,两两比较差异有统计学意义(P<0.05);Ki-67在正常子宫内膜仅有少量表达,在不典型增生子宫内膜中表达为33.33%和子宫内膜癌中表达为63.75%,差异均有统计学意义(P<0.05)。C-erbB-2及Ki-67的表达与子宫内膜癌的分化程度、临床分期、肌层浸润深度及淋巴结转移4种病理特征均有关(P<0.05)。结论　ER、PR、C-erbB-2和Ki-67表达与子宫内膜癌的临床病理相关,可作为判断子宫内膜癌预后及指导临床治疗的指标。