P57 kip2在葡萄胎中表达及临床意义

目的探讨P57 kip2在完全性葡萄胎(CM)、部分性葡萄胎(PM)及水肿流产绒毛(HA)诊断中的作用。方法应用免疫组化的方法检测P57蛋白在完全性葡萄胎28例,部分性葡萄胎30例,水肿绒毛30例组织中的表达,并应用胶体金免疫电镜技术观察P57 kip2在以上组织中的超微结构定位。结果 P57 kip2在30例HA 27例(90%)呈阳性表达,30例PM 25例(83.33%)呈阳性表达,28例CM 3例(10.71%)呈阳性表达,并且在CM中的阳性强度均较弱。3种病变P57 kip2染色阳性率统计分析显示CM与PM及HA之间均存在显著性差异(P<0.01),而PM与HA之间无显著性差异(P>0.05)。完全性葡萄胎细胞内质网和核膜上有黑色圆形集中的胶体金颗粒分布,部分性葡萄胎病变组织中无发现胶体金颗粒分布。结论 P57 kip2免疫组化是诊断CM的一种高敏感性、高特异性方法,同时用胶体金免疫电镜技术检测P-57kip2蛋白在CM的超微结构定位,对早期CM的发现有重大作用。     

葡萄胎基因印迹的研究进展

妊娠滋养细胞疾病（gestational trophoblastic disease,GTD）是一组来源于胚胎滋养细胞的疾病,一般包括葡萄胎（（hydatidiform mole,HM）,侵蚀性葡萄胎（invasive mole）,     

p57和p53蛋白在水肿性流产及葡萄胎鉴别诊断中的作用

目的探讨p57和p53蛋白在水肿性流产、完全性和部分性葡萄胎鉴别诊断中的作用。方法分别收集正常绒毛、水肿性流产、部分性葡萄胎和完全性葡萄胎石蜡标本10、12、23和20例,应用免疫组织化学EnVision法检测p57和p53蛋白在这些组织中的分布及表达水平。结果p57蛋白在正常绒毛、水肿性流产及部分性葡萄胎组织中主要分布于绒毛的细胞滋养细胞及间质细胞,阳性表达比例分别为10/10、12/12和100％( 23/23),各组间相比差异无统计学意义(P＞0.05)。在完全性葡萄胎中细胞滋养细胞及间质细胞p57表达缺失,与部分性葡萄胎相比,差异有统计学意义(P＜0.05)。p53蛋白主要表达于完全性和部分性葡萄胎的细胞滋养细胞及中间滋养细胞。在正常绒毛中p53蛋白呈阴性表达,水肿性流产中仅1例p53蛋白呈阳性表达(1/12),部分性葡萄胎和完全性葡萄胎中p53蛋白的阳性率分别为60.9％( 14/23)和85.0％ (17/20);p53蛋白的阳性率,部分性葡萄胎较水肿性流产明显增加,完全性葡萄胎较部分性葡萄胎也明显增加,差异均有统计学意义(均P ＜0.05)。结论p57蛋白免疫组织化学检测可辅助鉴别完全性和部分性葡萄胎,而p53蛋白的检测则有助于鉴别水肿性流产和部分性葡萄胎。     

PCNA和Caspase-3在妊娠滋养细胞疾病中的表达及意义

目的研究PCNA和Caspase-3在妊娠滋养细胞疾病中的表达变化及意义,为妊娠滋养细胞疾病早期诊断、预后判断提供理论依据。方法收集滋养细胞疾病标本50例,其中葡萄胎10例(均为完全性葡萄胎),侵蚀性葡萄胎20例,绒毛膜癌20例。正常早孕绒毛标本10例为对照组。应用免疫组织化学技术检测PCNA和Caspase-3在早孕绒毛、葡萄胎、侵蚀性葡萄胎、绒毛膜癌组织中的表达情况。结果 PCNA在正常早孕绒毛、葡萄胎、侵蚀性葡萄胎和绒癌中的表达分别为10.24%、20.70%、50.92%、53.65%,各组差异有统计学意义(P0.05)。Caspase-3在正常早孕绒毛、葡萄胎、侵蚀性葡萄胎和绒癌中的表达先升高又降低,分别为1.25%、2.60%、6.40%、1.90%,各组差异有统计学意义(P0.05)。结论 PCNA及Caspase-3表达异常,增殖/凋亡失衡是引起GTT的重要因素。     

印迹基因p57~(kip2)蛋白在水泡状胎块诊断和分型中作用

目的 探讨p57kip2蛋白表达在水泡状胎块诊断和分型中的作用和意义.方法 应用免疫组化SP法检测p57kip2蛋白30例在完全性水泡状胎块(complete hydatidiform moles,CHMs)、25例部分性水泡状胎块(partial hydatidiform mole,PHMs)和20例水泡状流产(hydropic abortions,HAs)三组病变中的表达情况,正常成熟胎盘(normal mature placentas,NMPs)为正常对照.结果 p57kip2蛋白在10例NMPs、20例HAs组织中的细胞滋养层细胞、绒毛间质细胞和绒毛外滋养细胞团核表达阳性,合体滋养层细胞不表达;CHMs的绒毛间质细胞和细胞滋养层细胞p57kip2蛋白不表达,阳性表达仅见于绒毛外散在滋养细胞团中;25例CHMs的绒毛间质细胞和细胞滋养层细胞p57kip2均表达阳性.结论 p57kip2蛋白在CHMs和PHMs的表达和分布有明显差异,可作为胎块分型诊断的客观辅助指标,值得在国内妇产科病理诊断常规工作中推广应用.     

脑星形细胞瘤中P27kip1、P57kip2、CyclinE表达与恶性程度及预后关系

目的探讨P27^kip1、P57^kip2、CyclinE在脑星形细胞瘤的表达情况，并结合多种临床因素探讨其与肿瘤恶性程度及预后的关系。方法采用S-P免疫组化技术，检测50例脑星形细胞瘤及10例正常脑组织中P27^kip1、P57^kip2、CycLinE的表达．结果P27^kip1、P57^kip2及CyclinE在脑星形细胞瘤阳性表达随恶性程度不同有显著差异（P〈0．01）。通过Spearman等级相关分析P27^kip1与P57^kip2，CyclinE与P57^kip^2表达联系之间具有相关性（P〈0．05）。通过单因素及多因素条件Logistic回归模型表明肿瘤的病理级别、星形细胞瘤中P27^kip1、CyclinE表达是影响脑星形细胞瘤预后的主要因素。结论脑星形细胞瘤中P27~ipl，P57“”及CyclinE表达与肿瘤恶性程度相关；P27^kip1、P57^kip2及CyclinE表达两两之间具有相关性；肿瘤的病理级别、星形细胞瘤中P27^kip1、CyclinE表达可作为评价脑星形细胞瘤预后的独立指标。     

MM P-2/TI MP-2及VEG F在滋养细胞疾病中的表达及意义

目的 检测不同滋养细胞疾病组织中MMP-2/TIMP-2及VEGF的表达情况,观察比较它们的表达特点,分析与滋养细胞疾病发生、发展的相关性.方法 收集30例正常绒毛;40例葡萄胎组织,30例手术切除的恶性葡萄胎组织,采用单克隆抗体免疫组化SP法对其染色,光镜下分别观察以上不同组织中MMP-2、TIMP-2、VEGF的阳性表达情况.结果 (1)从正常绒毛→良性葡萄胎→恶性葡萄胎,MMP-2的阳性率有升高趋势,差异有统计学意义(P＜0.05).VEGF的表达与MMP-2正相关.(2)TIMP-2的阳性表达在滋养细胞疾病内部不同分组间两两比较,差异均无统计学意义(P＞0.05).(3)MMP-2/TIMP-2组合同时阴性表达在良性葡萄胎中占65%(26/40),在恶性葡萄胎中占16.67%(5/30),两者比较有显著性差异(P＜0.01).MMP-2阳性表达伴TIMP-2阴性表达在良性葡萄胎中占2.5%(1/40),在恶性葡萄胎中占56.67%(17/30),两者比较有显著性差异(P＜0.01).结论 (1)MMP-2和VEGF共同参与了滋养细胞疾病的发生和发展.(2)MMP-2/TIMP-2两者联合检测对鉴别良、恶性滋养细胞疾病有重要价值.     

PCNA与Ki-67在葡萄胎患者宫内不同部位组织中的表达及临床意义

目的探讨PCNA和Ki-67在葡萄胎患者宫内不同部位组织中的表达对葡萄胎治疗及预后判断的意义.方法采用免疫组化S-P法检测38例葡萄胎患者宫腔中央水泡样胎块及靠宫壁蜕膜样组织中PCNA和Ki-67的表达.结果 1.PCNA及Ki-67在宫中央组织阳性表达均大于靠宫壁组织.P＜0.05,有明显差异.2.完全性葡萄胎PCNA及Ki-67阳性表达>部分性葡萄胎.浸润性葡萄胎PCNA及Ki-67阳性表达>完全性葡萄胎,且均为强阳性表达.3.PCNA和Ki-67在两组织中均有阳性表达,PCNA的表达更为明显,P＜0.05(宫内)P＜0.05(宫壁),有显著差异.结论葡萄胎宫内水泡样组织的增殖活性明显大于靠宫壁的组织,必须彻底刮净宫内组织方能预防恶变的发生.靠宫壁组织因其增殖活性较弱,可不必常规二次刮宫,以避免过度搔刮带来的过度损伤.葡萄胎的细胞增殖程度可能随疾病进展而逐渐增强,对于宫内、宫壁组织均有强阳性表达的患者要警惕其恶变的可能.PCNA与Ki-67能代表葡萄胎滋养细胞异常增生的客观指标,其检测简便、快捷、价廉,有临床价值,值得推广.     

妊娠滋养细胞肿瘤组织中cyclin D1、Rb蛋白产物的表达

目的：探讨增殖相关基因cyclin D1、Rb在妊娠滋养细胞肿瘤中的表达变化。方法：采用免疫组化S－P法,检测20例葡萄胎、15例侵蚀性葡萄胎、15例绒毛膜癌组织中两种基因蛋白产物的表达。结果：在恶性滋养细胞肿瘤组织中,cyclinD1的阳性表达率随临床期别的增高呈递增趋势,而Rb呈递减趋势,二者在Ⅲ期的阳性表达率与Ⅰ期及Ⅱ期相比差异均具有显著性（P＜0．05）;化疗可降低cyclinD1在恶性滋养细胞肿瘤中的阳性表达,而对Rb无影响。结论：cyclin D1的过表达,Rb的缺失在妊娠滋养细胞肿瘤的发展中可能有重要的生物学意义。     

水泡状胎块中p57、survivin、Ki-67的表达及意义

目的研究p57、survivin、Ki-67在完全性水泡状胎块(complete hydatidiform mole,CHM)和部分性水泡状胎块(partial hydatidiform mole,PHM)中的表达情况,探讨其在水泡状胎块(hydatidiform mole,HM)诊断中的意义。方法应用免疫组化法检测p57、survivin、Ki-67在32例CHM、21例PHM和20例正常早孕绒毛中的表达。结果 CHM组p57的表达明显低于PHM、正常组;CHM组survivin的表达明显高于正常组;CHM组、PHM组Ki-67的表达均明显高于正常组。结论 p57可作为CHM与PHM、正常早孕绒毛鉴别的有用指标,对于p57都表达的PHM、早孕流产绒毛的鉴别,检测survivin、Ki-67的表达水平可有一定帮助。     

P57kip2蛋白表达与水泡状胎块分型的关系

目的探讨P57kip2蛋白在水泡状胎块分型诊断中的作用。方法完全性和部分性水泡状胎块分别为78和42例,应用免疫组织化学SP法检测其P57kip2蛋白表达情况。结果P57kip2蛋白在完全性水泡状胎块中表达主要呈弱阳性,在部分性水泡状胎块中以强阳性为主,在部分性水泡状胎块中的阳性率为(92.86%),显著高于完全性水泡状胎块(P<0.01)。结论检测水泡状胎块中P57kip2蛋白表达,有助于水泡状胎块的分型和判断预后。     

p57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles

AIMS: To determine the utility of p57kip2 in the diagnosis of hydatidiform mole. p57kip2 protein is a cyclin-dependent kinase inhibitor (CDKI) and is strongly paternally imprinted, being expressed from the maternal allele. It has been hypothesized that complete mole (CHM) with only the paternal genome would display reduced or nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes. METHODS AND RESULTS: The immunohistochemical expression of p57kip2 protein was investigated using paraffin-embedded tissue sections in histologically unequivocal cases of CHM (n = 51), PHM (n = 7), invasive mole (n = 1), and hydropic miscarriage (n = 2), as well as in histologically undetermined cases (n = 9). In the histologically unequivocal complete and invasive moles, expression of p57kip2 was absent except for one case in which villous cytotrophoblast covering the villous stroma was positive (51/52) as well as villous stromal cells (51/52). In contrast, it was strongly and continuously expressed in both villous cytotrophoblast and stromal cells in all cases of PHM and hydropic miscarriage. Among the nine histologically undetermined cases, five cases showing p57kip2 immunopositivity and hyperploid DNA were classified as PHMs, two cases showing p57kip2 immunonegativity and hyperploidy as CHMs, and two cases with p57kip2 immunopositivity and diploid DNA as hydropic miscarriage and diploid PHM, respectively, upon review of the histopathological findings. Intermediate trophoblast forming trophoblastic columns or anchoring villi and extravillous trophoblast at the implantation site showed variable expression of p57kip2 in all gestational conditions. Maternal decidua showed diffuse and strong p57kip2 expression, whereas syncytiotrophoblast was completely negative in all cases regardless of the diagnosis. CONCLUSIONS: In summary, p57kip2 immunostaining results correlated well with morphological features of molar pregnancies and were helpful in determining histologically equivocal cases.     

Minichromosome maintenance protein 7 expression in gestational trophoblastic disease: correlation with Ki67, PCNA and clinicopathological parameters

AIMS: To assess the proliferative activity of gestational trophoblastic disease (GTD) using one of the novel proliferation markers (MCM7) and to determine its prognostic value in hydatidiform mole (HM). METHODS AND RESULTS: Immunohistochemical staining for MCM7 was performed on 122 samples of paraffin-embedded trophoblastic tissues including 22 normal first-trimester placentas, 12 term placentas, 12 spontaneous miscarriages (SM), 21 partial moles (PM), 44 complete hydatidiform moles (CM), and 11 choriocarcinomas (CCA). The correlations between the proliferative indices assessed by MCM7, proliferating cell nuclear antigen (PCNA) and Ki67 (MIB1) immunoreactivity as well as clinical progress were assessed. MCM7 immunoreactivity was found predominantly in the nuclei of cytotrophoblast and intermediate trophoblast and decreased with placental maturation. MCM7 expression was highest in CCA, followed by CM, PM, normal first-trimester placenta, SM and term placenta. MCM7 index was significantly higher in PM and CM than in SM (P = 0.007, P < 0.001) but not between PM and CM themselves (P = 0.560). Eighteen of the 65 patients with HM developed persistent trophoblastic disease (PTD) requiring chemotherapy. There was no significant difference in MCM7 indices between the patients who developed PTD and those who did not (P = 0.312). MCM7 indices correlated well with Ki67 (P = 0.002) but not with PCNA (P = 0.054) indices. MCM7 indices demonstrated less variability than PCNA and Ki67 and may be a better proliferation marker than the latter two. CONCLUSIONS: We conclude that MCM7 is useful in differentiating molar and non-molar gestations but is not helpful in discriminating PM from CM or in predicting PTD.     

p57(KIP2) immunohistochemical staining of gestational trophoblastic tumours does not identify the type of the causative pregnancy

AIM: To determine whether immunohistochemical staining for p57(KIP2), the product of the maternally expressed gene CDKN1C, can be used to differentiate between gestational trophoblastic tumours arising from a complete hydatidiform mole and those originating from non-molar pregnancies. METHODS: The immunohistochemical expression of p57(KIP2) was investigated in 23 cases of choriocarcinoma and 17 placental site trophoblastic tumours. Fourteen of the tumours examined were shown by DNA analysis to have arisen from complete hydatidiform moles and 26 from non-molar pregnancies. RESULTS: Five of 11 (45%) post-complete hydatidiform mole choriocarcinomas and two of three (67%) post-complete hydatidiform mole placental site trophoblastic tumours were found to be p57(KIP2)+ and showed similar immunostaining characteristics to tumours that developed from non-molar pregnancies. Although there was a statistically significant reduction in the proportion of cases showing positive p57(KIP2) staining in post-complete hydatidiform mole tumours compared with those originating in non-molar pregnancies [proportion difference 0.35 [95% confidence interval (CI) 0.05, 0.61], P = 0.02], immunostaining did not provide diagnostically useful information to differentiate between these tumours in clinical practice. There was no significant difference between the extent of staining in choriocarcinoma versus placental site trophoblastic tumours [proportion difference 0.17 (95% CI - 12, 42), P = 0.19]. The majority of both types of gestational trophoblastic tumour were positive for the presence of the p57(KIP2) protein irrespective of their genetic origin. CONCLUSION: Immunostaining for p57(KIP2) fails to discriminate between gestational trophoblastic tumours that have arisen from complete hydatidiform moles and those that have originated from other types of pregnancy.     

p27kip1、p16蛋白和增殖细胞核抗原在鼻咽癌中的表达及其意义

目的 研究p27^kip1、p16蛋白及增殖细胞核抗原(PCNA)在鼻咽癌(NPC)组织中的表达,探讨它们之间的关系及其与．NPC生物学行为及预后的相关性。方法应用免疫组织化学EnVision两步法检测66例鼻咽非角化性癌(NKC)组织和25例鼻咽黏膜慢性炎症(NP)组织中p27^kip1、p16蛋白及PCNA表达水平。结果(1)．NKC组织中p27^kip1、p16阳性表达率分别为65％、68％;与NP组比较,差异有统计学意义(P＜0．05)。(2)＜、p16蛋白在NKC中的表达与NKC颅神经侵犯及治疗后5年生存率有关(P＜0．05),与临床分期、淋巴结转移无关(P＞0．05);PCNA表达与．NKC临床分期及治疗后5年生存率有关(P＜0．05),与淋巴结转移、颅神经侵犯无关(P＞0．05)。(3)p27^kip1、p16及PCNA阳性表达之间有相关性(P＜0．05)。结论检测p27^kip1、p16蛋白及PCNA有助于综合评估NKC的预后。     

妊娠滋养细胞肿瘤中E-cadherin和增殖细胞核抗原的表达

目的：研究妊娠滋养细胞肿瘤(GTT)中E-cadherin与PCNA的表达意义。方法：采用免疫组化SP法检测了妊娠滋养细胞肿瘤中E-cadherin与PCNA的表达。结果：E-cadherin在正常早期绒毛(NP)及其肿瘤(CM、IM、OCA)中表达率分别为56．29％、42．07％、19．30％、7．14％，各组间差异非常显著。PCNA在NP、CM、IM和OCA中表达率分别为10．40％、20．76％、53．60％、51．95％，各组间差异非常显著。E-cadherin与PCNA阳性率呈负相关。结论：E-cadherin和PCNA的检测有助于良恶性GTT的鉴别；E-cadherin表达减弱或消失促进了GTT的增殖活性。     

P57kip2 immunohistochemical expression and ultrastructural findings of gestational trophoblastic disease and related disorders

Gestational trophoblastic disease (GTD) is a unique spectrum of diseases ranging from complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and invasive mole (IM) to choriocarcinoma (CC). Placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) have been classified as related disorders. Mesenchymal dysplasia (MD) may be misdiagnosed as PHM; however, it is said to have a quite different histogenesis from PHM. P57kip2 is the protein product of a paternally imprinted or maternal gene that inhibits cyclin-dependent kinases (CDK), thus serving to inhibit cell proliferation and to suppress tumor growth. Its lack of expression in trophoblastic disease plays a role in its abnormal proliferation and differentiation. In this study, P57kip2 immunostaining was absent in the trophoblastic layers of CHM and was positive in the trophoblast layer of nonmolar villi and MD. Ultrastructure of complete molar cystic villi showed tree-like branching of microvillous processes and intracytoplasmic lacunae without capillaries in the stroma, whereas MD contained many newly formed blood vessels and collagen. Also, large lacunae with microvilli and polymorphic nuclei of syncytiotrophoblast cells with well-developed organelles were observed in IM. Lung ETT following CHM and normal deliveries showed two types of large mononuclear cells and binuclear cells with abundant organelles and bundles of intermediate-type filaments in the stroma.     

The usefulness of p57 immunohistochemical staining and genotyping test in the diagnosis of the hydatidiform mole

Classification of molar gestations into complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) and their differentiation from nonmolar hydropic abortions (HA) are traditionally accomplished by morphology alone. Sometimes, the process may be inaccurate or inconclusive especially in early diagnosed cases. With the availability of p57^KIP2 immunostaining (the product of a strongly paternally imprinted and maternally expressed gene), it may be possible to classify these lesions objectively. P57^KIP2 immunostaining is absent in CHM because it lacks a maternal genome, whereas PHM and HA show positive staining. The aims of this study were to evaluate the results of routine histopathological examination and p57^KIP2 immunoreactivity in a large series of molar and nonmolar HA in Tunisia, and to compare the accuracy of p57^KIP2 immunohistochemistry with that of nuclear DNA microsatellite polymorphism in identifying CHM. The immunohistochemical expression of p57^KIP2 protein was investigated in 220 specimens of first trimester hydropic abortuses, and it was compared with the original diagnosis based on morphology, including 132 CHM, 49 PHM, and 39 HA. Concordant results were obtained in 210 cases. In 9 of 10 cases with a discordant diagnosis (negative immunostaining in 8 cases morphologically diagnosed as PHM and one case diagnosed as HA), microsatellite DNA genotyping analysis agreed with the results of p57^KIP2 staining, confirming the diagnosis of CHM in these cases. Twenty cases of CHM with negative p57^KIP2 immunostaining were also analyzed by genotyping and indicated the absence of maternal contribution and the homozygosity for a single paternal allele in concordance with the androgenetic and monospermic origin of CHM in these cases. We confirm that for distinguishing CHM from its mimics, p57^KIP2 immunohistochemistry can be used as successfully as DNA microsatellite genotyping. However, molecular techniques are still required for the evaluation of some difficult cases with discordant positive p57^KIP2 staining.