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。     

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。     

KCNQ1、p57~(KIP2)蛋白在水泡状胎块中的表达及意义

目的 观察母系印迹基因KCNQ1和p57KIP2在正常绒毛及水泡状胎块组织中蛋白的表达情况,探讨检测KCNQ1、p57KIP2蛋白对鉴别不同类型水泡状胎块组织的意义.方法 用免疫组化方法检测KCNQ1、p57KIP2蛋白在30例正常早孕绒毛组织、56例完全性水泡状胎块和26例部分性水泡状胎块中的表达情况,然后用多组秩和检验计算其与临床分型的关系.结果 KCNQ1、p57KIP2蛋白在完全性水泡状胎块中的表达明显低于正常早孕绒毛和部分性水泡状胎块.而在部分性水泡状胎块和正常早孕绒毛间,两者的表达呈正相关(P<0.01).结论 KCNQ1、p57KIP2蛋白在水泡状胎块组织中的表达与其临床分型显著相关,联合检测p57KIP2、KCNQ1对鉴别不同类型的水泡状胎块有临床意义.     

水泡状胎块的分子病理诊断与研究进展

水泡状胎块(hydatidiform moles)是一组与妊娠相关的滋养细胞疾病,根据组织学形态和免疫组化等辅助手段诊断可重复性不高。该文就水泡状胎块的常规辅助诊断方法、分子病理诊断及研究进展进行综述,重点介绍STR基因分型检测在水泡状胎块诊断和分型中的应用及水泡状胎块发生、恶性进展相关机制的研究进展。     

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。     

间质细胞凋亡联合滋养叶细胞增殖基因检测对水泡状胎块诊断的意义

目的分析联合间质细胞凋亡及滋养叶细胞增殖有关基因检测在水泡状胎块(Hydatidiform Mole,HM)中的诊断价值。方法采用整群抽样法抽选2019.01-2020.04本院收治的HM患者共98例进行研究,将其中60例完全性HM设为完全性HM组,余下38例部分性HM设为部分性HM组,另选取同时间段被本院收治的50例绒毛水肿患者设为绒毛水肿组,统计并比较三组胎块Ki67、Bcl-2以及Livin表达、间质细胞凋亡情况与Ki67、Bcl-2以及Livin和凋亡指数(AI)间的相关性。结果三组胎块在Bcl-2以及Livin表达方面差异不显著(P0.05);部分性HM组、完全性HM的Ki67表达较绒毛水肿组明显升高(P0.05),且完全性HM组Ki67表达比部分性HM组更高(P0.05);绒毛水肿组的绒毛间质中基本未观察到凋亡细胞,而部分性及完全性HM组可观察到凋亡细胞,呈现散在分布。部分性及完全性HM组的AI较绒毛水肿组有明显升高(P0.05),但部分性及完全性HM组AI对比差异不显著(P0.05);Ki67、Bcl-2以及Livin和AI之间均为正相关关系(r=0.530、0.328、0.280,P0.05)。结论联合间质细胞凋亡及滋养叶细胞增殖有关基因检测不仅能应用到HM诊断和分型中,也能应用到HM和绒毛水肿的鉴别诊断中,在临床上有着重要的诊断价值。     

PCNA和P57^kip2在葡萄胎中表达的研究

目的探讨PCNA（增殖细胞核抗原,proliferation cell nuclear antigen）和P57^kip2在CM（完全性葡萄胎,com-plete hydatidiform mole）及PM（部分性葡萄胎,partial hydatidiform mole）中的表达及意义。方法应用免疫组化的方法检测PCNA及P57^kip2蛋白在CM、PM及HA（水肿绒毛,hydrops trophonema）组织中的表达。结果 PCNA在所有组织切片中均见到。PCNA主要在细胞滋养层细胞及中间型滋养细胞表达。PI在HA中最低,于PM中增高,CM中达到最高。其中CM与PM及与HA之间,差异均有统计学意义（P〈0.05）。而PM与HA之间无显著性差异（P〉0.05）。P57^kip2在30例HA27例呈阳性表达（90%）,30例PM 25例呈阳性表达（83.33%）,28例CM 3例呈阳性表达（10.71%）,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）。结论 PCNA与P57^kip2能代表葡萄胎滋养细胞异常增生的客观指标,P57^kip2蛋白的低表达和PCNA的高表达可能在葡萄胎的的发生发展中起重要作用,两者的共同检测对早期CM的发现有重大作用。     

P57和Ki-67在葡萄胎鉴别诊断中的作用

目的:探讨P57和Ki-67蛋白在完全性和部分性葡萄胎鉴别诊断中的作用.方法:分别收集正常胎盘绒毛、部分性葡萄胎和完全性葡萄胎石蜡标本各12例,应用免疫组织化学方法检测P57和Ki-67蛋白在这些病变中的分布及表达水平.结果:P57蛋白在正常绒毛及部分性葡萄胎组织中主要分布于绒毛的细胞滋养叶细胞及间质细胞,两组间阳性率...     

人子宫内膜癌中p57 kip2、Cyclin D1的表达及意义

目的：探讨p57 kip2、Cyclin D1在人子宫内膜癌发生、发展中的作用。方法选取子宫内膜样腺癌( endometrioid adenocar-cinoma, EA)100例、子宫内膜上皮内瘤变(endometrial intraepithelial neoplasia, EIN)20例、子宫内膜增生性病变20例、增生期子宫内膜组织20例;选取不同子宫内膜细胞[高分化子宫内膜癌细胞( Ishikawa)、中分化子宫内膜癌细胞( JEC)、低分化子宫内膜癌细胞(KLE)及正常子宫内膜细胞(ESC)]进行细胞培养。应用免疫组化EliVision法检测不同子宫内膜组织中p57kip2、Cyclin D1蛋白的表达;Western blot法检测不同子宫内膜细胞中p57 kip2、Cyclin D1蛋白的表达。结果 p57 kip2蛋白在EIN组织中表达最高,在增生期子宫内膜、EA、子宫内膜增生性病变组织中表达逐渐降低,子宫内膜增生性病变与EIN组织中p57 kip2蛋白表达差异有统计学意义(P<0.05)。 Cyclin D1蛋白在EA组织中表达最高,在增生期子宫内膜组织中表达最低,在子宫内膜增生性病变组织、EIN组织中表达依次增高,差异均有显著性( P<0.01)。 p57 kip2、Cyclin D1蛋白在EA组织中的表达随着组织学分级的增高呈依次递减趋势,但仅p57 kip2蛋白表达和组织学分级有关( P<0.05)。 p57 kip2蛋白在KLE中表达最高,在ESC中表达最低,两组相比差异有显著性( P<0.05);Cyclin D1在JEC、Ishikawa中的表达高于ESC,差异均有显著性( P<0.05)。结论 p57kip2、Cyclin D1均参与子宫内膜癌的发生、发展。 Cyclin D1表达是子宫内膜癌发生的早期事件,可能还存在异常合成的p57 kip2蛋白,其协同Cyclin D1促进子宫内膜的恶性转化。联合检测p57 kip2、Cyclin D1在子宫内膜癌中的表达,对预测子宫内膜癌患者预后有一定的临床意义。     

滋养组织中转录因子GATA3的表达及意义

目的探讨转录因子GATA3在滋养组织中的表达及其鉴别诊断价值。方法运用免疫组化EnVision法检测GATA3在91例滋养组织中的表达,包括30例正常胎盘组织、30例水泡状胎块、18例绒毛膜癌、3例胎盘部位滋养细胞肿瘤、5例胎盘部位结节及5例超常胎盘部位;同时检测30例子宫颈癌及30例子宫内膜癌中GATA3的表达。结果 GATA3在早期胎盘组织中呈弥漫强阳性,成熟绒毛中表达明显减弱,但在胎盘部位呈持续强阳性。61例滋养细胞疾病中,仅1例绒毛膜癌阴性,其余病例均为阳性;阳性细胞主要定位于细胞滋养细胞和中间型滋养细胞,合体滋养细胞基本不着色。子宫内膜癌中无GATA3阳性病例;3例子宫颈鳞状细胞癌呈弱至中等的局灶着色,子宫颈腺癌中GATA3均呈阴性。GATA3在滋养细胞病变中敏感性及特异性分别为98.36%及95.00%。结论 GATA3是滋养细胞较为敏感及特异的标志物,不能区分不同类型的滋养细胞疾病,但可鉴别滋养细胞疾病及苗勒管起源的恶性肿瘤。     

Hydatidiform moles: differential diagnosis,diagnostic reproducibility,genetics and ancillary techniques to refine diagnosis

Distinction of hydatidiform moles from non-molar specimens and sub-classification of hydatidiform moles as complete hydatidiform mole (CHM) versus partial hydatidiform mole (PHM) are important. Risk of persistent gestational trophoblastic disease and clinical management differ for these entities. Diagnosis based on morphology is subject to interobserver variability. The unique genetics of CHMs, PHMs, and non-molar specimens allow for certain techniques, including immunohistochemical analysis of p57 expression and PCR-based DNA genotyping, to refine diagnosis. p57 immunostaining identifies CHMs, which lack p57 expression due to lack of maternal DNA, but does not distinguish PHMs from non-molar specimens since both express p57 due to the presence of maternal DNA. Genotyping distinguishes purely androgenetic CHMs from diandric triploid PHMs and both of these from biparental non-molar specimens by comparing villous and decidual DNA patterns to determine the parental source and ratios of polymorphic alleles. An algorithmic approach using these ancillary techniques is advocated.     

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.     

Differential diagnosis between complete and partial mole by TSSC3 antibody completely correlates to DNA diagnosis.

Complete hydatidiform moles (CHMs) are a type of androgenetic fertilization without an ovum. Cases of CHM exhibit a generalized swelling of the villi and are known to be highly associated with persistent disease or carcinoma. In contrast, partial hydatidiform moles (PHMs) also show characteristic hydropic changes among the villi, but the incidence of secondary disease is relatively low. Because PHMs are fertilized by one ovum and two sperm and CHMs are fertilized by one or two sperm alone, we considered whether or not maternally imprinted genes might be useful for achieving a differential diagnosis. The validity of the imprinted genes in CHMs was assessed by implementation of a microarray technique. Among the genes examined, TSSC3, SLC22A1L, KCNQ1, and Decorin were shown to be down-regulated, and TSSC3 was the most markedly suppressed of these genes. In this study, 20 cases of CHM, the diagnosis of which was confirmed by DNA polymorphism, were investigated. In all of these cases, the expression of TSSC3 was completely absent, as determined by Western blot analysis. Conversely, 12 cases of PHM, also diagnosed by DNA polymorphism, were examined here; in all of these 12 cases, TSSC3 was found to be expressed normally. Immunohistochemical (IHC) analysis also produced the same results. The complete silencing of TSSC3 in cases of CHM will provide a novel, convenient strategy for the diagnosis of molar lesions in the placenta.     

P57KIP2 immunostaining and molecular cytogenetics: combined approach aids in diagnosis of morphologically challenging cases with molar phenotype and in detecting androgenetic cell lines in mosaic/chimeric conceptions

Although molar pregnancies are typically defined by morphological, histologic, and genetic criteria, most cases are diagnosed solely on histologic findings. Recently, several studies have demonstrated the usefulness of p57KIP2 immunostaining as an ancillary diagnostic tool for molar pregnancies. The p57KIP2 gene is paternally imprinted and maternally expressed; therefore, the positive staining of its protein indicates the presence of a functional maternal allele. Because complete hydatidiform moles (CHMs) lack a maternal genome, p57KIP2 immunostaining is absent. Previous studies have validated this staining technique by demonstrating differential nuclear expression in CHMs versus non-CHMs; however, these studies have not included cytogenetic analysis. We report on 58 cases of hydropic placentas, correlating cytogenetic and p57KIP2 immunostaining results. In addition, cases with unusual p57KIP2 staining patterns are discussed. Also included are 2 mosaic conceptions (1 diploid/triploid and 1 diploid/tetraploid), 6 chimeric/mosaic conceptions with androgenetic/biparental cell lines, and 2 cases of placental mesenchymal dysplasia.     

Complete hydatidiform mole retaining a chromosome 11 of maternal origin: molecular genetic analysis of a case.

Hydatidiform moles are pregnancies characterized by abnormal development of both embryonic and extraembryonic tissues and are associated with the misexpression of imprinted genes. The vast majority of complete hydatidiform moles are diploid and androgenetic, whereas partial hydatidiform moles are triploid, with an extra set of chromosomes of paternal origin. Here, we present an unusual complete mole that showed strong expression of two imprinted, maternally transcribed genes, CDKN1C (encoding p57(KIP2)) and PHLDA2 (TSSC3/IPL), both part of a large imprinted gene domain on chromosome 11. Using microsatellite genotyping and fluorescent in situ hybridization, we show that this paradoxical gene expression was due to retention of a maternal copy of chromosome 11 in addition to the two paternal copies normally present in complete moles. These findings demonstrate that, despite being predominantly androgenetic, some complete moles contain small amounts of DNA of maternal origin. Furthermore, these results provide an explanation for rare false negatives that can arise when p57(KIP2) is used as a diagnostic marker for complete moles.     

Genetic study of hydatidiform moles by restriction fragment length polymorphisms (RFLPs) analysis.

Twenty three hydatidiform moles (HMs) were studied using the techniques of "RFLPs" employing a minisatellite deoxyribonucleic acid probe. Among the 23 HMs, 17 were homozygous types resulting from a duplicated haploid sperm, and two were heterozygous types resulting from fertilization two independent sperms (dispermy). It was revealed that the four histopathologically diagnosed complete HMs (CHMs) were partial HMs (PHMs) with one maternal and 2 paternal chromosome contribution (diandry) or two maternal and 1 paternal alleles (digyny). The locus specific minisatellite probes were useful in classifying CHM into heterozygous and homozygous types as well as in diagnosing PHM. One heterozygous (50%) and 5 homozygous (29.4%) CHMs, and one PHM (25%) progressed to persistent gestational trophoblastic disease (p > 0.5).     

Gestational trophoblastic diseases: update on new immunohistochemical findings

Recent advances in the immunohistochemical analysis of gestational trophoblastic diseases allow pathologists to classify more accurately specific types of gestational trophoblastic lesions. The morphologic features of some forms of gestational trophoblastic tumours are dependent on the parental origin of the genetic contributions. Genomic imprinting results in the production of certain protein products based on the parental genetic origin. By analysing the protein product of an imprinted gene, such as p57^kip2, a hydatidiform mole may be classified as complete or partial. In addition, we review CD 34, p53, bcl-2, Bax, p21^waf1/cip1 and PCNA immunohistochemical expression in complete hydatidiform moles. A similar immunohistochemical review is performed for partial hydatidiform moles. We discuss the implications of various immunohistochemical findings in the nonvillous trophoblastic tumours: placental site trophoblastic tumour, epithelioid trophoblastic tumour and choriocarcinoma. Specific antibodies reviewed in detail for these lesions include inhibin-alpha, CK 18, MIB-1 (Ki-67), Mel-CAM, cyclins A, B, D1 and E, cdk 2 and 4, and p53. In summary, advances in immunohistochemistry aid the histopathologist in correctly classifying gestational trophoblastic tumours.     

p57KIP2表达结合流式细胞术分析对葡萄胎的辅助诊断价值

目的 研究父源性印迹基因p57KIP2蛋白表达结合DNA倍体分析对葡萄胎的辅助诊断意义.方法 收集32例具有DNA多态性遗传学分析资料的胎盘绒毛水肿病例,以遗传学分析结果作为葡萄胎的诊断依据.全部病例进行常规组织学检查、p57KIP2免疫组织化学染色(EnVision法)及流式细胞术DNA倍体分析,采用双盲法与遗传学分析结果对照.结果 32例绒毛水肿病例的遗传学分析证明,21例为完全性葡萄胎(CHM),7例为部分性葡萄胎(PHM),4例为水肿性流产.CHM p57KIP2免疫组织化学表达的阴性率为95.2%(20/21).非CHM的p57KIP2免疫组织化学全部阳性(11/11).p57KIP2免疫组织化学与DNA多态性分析结果的吻合率为96.9%(31/32).流式细胞术分析发现,7例PHM均为三倍体核型;21例CHM中有14例为二倍体,7例为四倍体;4例水肿性流产均为二倍体或近二倍体.结论 p57KIP2免疫组织化学阴性是CHM的可靠标志物.p57KIP2免疫组织化学结合流式细胞倍体分析可明确区分三种胎盘绒毛水肿性病变.p57KIP2免疫组织化学阴性支持CHM,p57KIP2免疫组织化学阳性且为三倍体为PHM,p57KIP2阳性且为二倍体支持水肿性流产.     

p57KIP2表达结合流式细胞术分析对葡萄胎的辅助诊断价值

目的 研究父源性印迹基因p57KIP2蛋白表达结合DNA倍体分析对葡萄胎的辅助诊断意义.方法 收集32例具有DNA多态性遗传学分析资料的胎盘绒毛水肿病例,以遗传学分析结果作为葡萄胎的诊断依据.全部病例进行常规组织学检查、p57KIP2免疫组织化学染色(EnVision法)及流式细胞术DNA倍体分析,采用双盲法与遗传学分析结果对照.结果 32例绒毛水肿病例的遗传学分析证明,21例为完全性葡萄胎(CHM),7例为部分性葡萄胎(PHM),4例为水肿性流产.CHM p57KIP2免疫组织化学表达的阴性率为95.2%(20/21).非CHM的p57KIP2免疫组织化学全部阳性(11/11).p57KIP2免疫组织化学与DNA多态性分析结果的吻合率为96.9%(31/32).流式细胞术分析发现,7例PHM均为三倍体核型;21例CHM中有14例为二倍体,7例为四倍体;4例水肿性流产均为二倍体或近二倍体.结论 p57KIP2免疫组织化学阴性是CHM的可靠标志物.p57KIP2免疫组织化学结合流式细胞倍体分析可明确区分三种胎盘绒毛水肿性病变.p57KIP2免疫组织化学阴性支持CHM,p57KIP2免疫组织化学阳性且为三倍体为PHM,p57KIP2阳性且为二倍体支持水肿性流产.