Flow cytometric diagnosis of partial mole.

To differentiate histologically partial hydatidiform moles (PM) and complete hydatidiform moles (CM) may be difficult. Cytogenetic studies have shown that PMs often had a triploid karyotype while CMs were always diploid. We assessed the DNA content of 31 paraffin-embedded cases of trophoblastic disease with flow cytometry. Twenty-four cases were histologically diagnosed as PM, 3 cases as CM; the others as hydropic abortion (2 cases), choriocarcinoma (1 case), and persistent trophoblastic disease (1 case). Four normal term placentas were used as diploidy controls. In 9 cases the results of the cytogenetic analysis were available. All placental specimens included also maternal tissue as an internal control. Eight of the 24 histologically diagnosed PMs were triploid; there was agreement in 8 cases out of 9 (90%) between the flow cytometric analysis and the karyotypic determination of ploidy. All normal controls as well as the hydropic abortion, the CM and the persistent trophoblastic disease were diploid. Abnormal content of DNA (DI = 1.3) was observed in the choriocarcinoma. Our results show that flow cytometric analysis of DNA content is a reliable and fast method of diagnosing PM on paraffin-embedded material.     

Hydatidiform mole: parental chromosome aberrations in partial and complete moles.

The relationship between parental constitutional chromosome abnormalities and the development of hydatidiform mole was evaluated in series from four institutions. Karyotype analysis was performed on blood samples from 237 patients with a pathological diagnosis of complete mole and 217 of their spouses. One patient was found to have a constitutional balanced translocation, t(11;18), while one spouse was found to have a balanced translocation, t(4;20). Among 125 patients with partial mole and 106 of their spouses, one male was found to be a translocation carrier, t(13;14). No significant increase in the frequency of translocations in the parents of complete moles was found in any of the series considered separately or together. Data from the combined series show no evidence of constitutional parental chromosome aberrations as an aetiological factor in the development of molar pregnancies.     

Subsequent pregnancy outcome in patients with spontaneous resolution of HCG after evacuation of hydatidiform mole: comparison between complete and partial mole

This study compared subsequent pregnancy outcome in patients with complete and partial hydatidiform moles. Among 1052 patients with molar pregnancy (complete mole, 801; partial mole, 251) monitored at Chiba University Hospital between 1981 and 1999, 891 patients (84.7%) had spontaneous resolution of human chorionic gonadotrophin (HCG) after mole evacuation, and 161 patients (15.3%) required chemotherapy. Of the 891 patients, 438 (49.2%) had 650 subsequent pregnancies. The pregnancy outcome was not significantly different in patients with complete and partial moles, and was comparable with that in the general Japanese population. The incidence of repeat molar pregnancy in patients with complete and partial mole (1.3 and 1.5% respectively) was 5-fold higher than that of the general population, while no increased risk of persistent gestational trophoblastic tumour (GTT) associated with later molar pregnancy was observed. During HCG follow-up, 10 patients (1.1%) developed secondary high-risk GTT between 14 and 54 months after mole evacuation. The incidence of high-risk GTT in patients with and without subsequent pregnancies was 0.46% (2/438) and 1.8% (8/453) respectively (P = 0.1243). In conclusion, patients with complete and partial mole can anticipate a normal future reproductive outcome, and pregnancies after experiencing hydatidiform mole may not affect the development of high-risk GTT.     

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。     

Vasculogenesis in complete and partial hydatidiform mole pregnancies studied with CD34 immunohistochemistry

BACKGROUND: Defective chorionic villous vascularization is present in pregnancies complicated by absent or abnormal embryonic development. The aim of this study was to investigate the embryonic and/or maternal genomic influence on vasculogenesis in diploid complete hydatidiform mole (CHM) and in triploid partial hydatidiform mole (PHM) in comparison with normal development. METHODS: Mean villous stromal area and functional vascular area, vessels with a lumen and haemangiogenetic cords, peripherally or centrally located were measured and counted in chorionic villi of 12 CHM, 12 normal pregnancies (termination of pregnancy, TOP) and 15 PHM of which nine were without an embryo (PHM-E) and six were with an embryo (PHM + E), using quantitative CD34 immunohistochemistry. RESULTS: TOP showed significantly more vessels per chorionic villus, centrally and peripherally located (median, range), than CHM, PHM-E and PHM + E (4.0, 0-9 versus 0.0, 0-11, 0.0, 0-18 and 1.0, 0-21). CHM showed significantly more centrally located cords than PHM-E, PHM + E and TOP (1.5, 0-22 versus 1.0, 0-15, 0.5, 0-8 and 1.0, 0-2). CONCLUSIONS: Initiation of chorionic villous vasculogenesis is independent of the maternal genome (CHM). The development of an embryo, however, is obligatory for the modulation of normal vascularization resulting in a well developed vasculosyncytial membrane.     

Differential diagnosis of chorionepithelioma of the uterus and hydatidiform mole by an immunologic test

Polysaccharide complexes obtained by Westphal's method in the modification of L. A. Zil'ber et al. from tissues of the primary tumor node and distant metastases (lungs) of a chorionepithelioma of the uterus were used for the differential diagnosis between chorionepithelioma and hydatidiform mole. The reaction to intradermal injection of polysaccharide complexes obtained from distant metastases (lungs) of the uterine chorionepithelioma possess high specificity and sensitivity: a positive reaction developed only in patients with chorionepithelioma of the uterus and it was negative in patients with hydatidiform mole. During a marked decrease in size of the metastases in the lungs in the course of chemotherapy, when the immunologic reaction for chorionic gonadotropin fell to 300–100 i.u./liter urine, the reaction to intradermal injection of the polysaccharide complexes from the metastases of the uterine chorionepithelioma still remained positive.Laboratory of Experimental Endocrinology, Department of Gynecology, Institute of Experimental and Clinical Oncology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 79, No. 1, pp. 60–63, January, 1975.     

Epidemiological study of complete and partial hydatidiform mole in Abu Dhabi: influence age and ethnic group.

An unmatched case control study of molar pregnancy was carried out at this hospital between 1978 and 1987 to investigate the influence of maternal age and ethnic group on the incidence of complete and partial hydatidiform mole. The age specific incidence of complete mole was minimal between the ages of 30 and 34 years (relative risk 1), showed a minor peak in teenagers (relative risk 3.1, 95% confidence interval 6.5-1.4), and a major peak in those of 35 years and over. Between 35 and 39 years the relative risk was 2.5 (95% CI 6.2-1.0) and at 40 years or more the relative risk was 9.8 (95% CI 28.9-3.3). No age group showed a significantly increased risk of partial mole. The women of Abu Dhabi had increased risks of both forms of molar pregnancy relative to women in Nottingham, England (relative risk 1): the risk of complete mole was increased threefold (95% CI 4.2-2.2) and that of partial mole twofold (95% CI 4.0-1.2). The increased risk of complete mole was greatest in Gulf Arabs (mainly Omanis and Yemenis) who had a sixfold increase in crude relative risk (95% CI 10.7-3.5). The increased risks of complete mole associated with maternal ethnic group remained after adjustment for maternal age distribution.     

Differential neutralizing antibody responses to varicella-zoster virus glycoproteins B and E following naked DNA immunization.

The only available vaccine against varicella-zoster virus (VZV) consists of the VZV-Oka attenuated but persistent virus strain. Development of a safer, subunit vaccine is therefore desirable. In this prospect, nucleic acid vaccines, expressing truncated forms of VZV glycoproteins B (recgB) and E (recgE) from which the anchor and the cytoplasmic domains were deleted, were used to immunize mice. Vaccination with recgB encoding plasmid elicited a strong and specific humoral immune response. Total IgG and neutralizing titres were comparable to those previously obtained by vaccination with purified and adjuvanted native recgB. In contrast, mice immunization with recgE encoding plasmid only induced a very weak immune response whereas we previously showed that vaccination with adjuvanted native or denatured recgE protein led to high neutralizing titres. The weakness of the immune response induced by recgE-encoding plasmid depended neither on the deletion of the anchor domain in the gE gene nor on the animal model. Analysis of antibody isotypes produced by plasmid immunizations revealed a response slightly dominated by IgG2a. Taken together, the data indicate that a VZV subunit vaccine based on adjuvanted recombinant glycoprotein E is more promising than a nucleic acid-based vaccine strategy. As regards recgB, both vaccination approaches might be appropriate.     

Early partial hydatidiform mole: prevalence, histopathology, DNA ploidy, and persistence rate

The widespread use of ultrasound in the diagnosis and management of intrauterine fetal death has resulted in moles being evacuated earlier than before. In order to clarify clinicopathologic features of early partial mole (PM), morphology and DNA ploidy of early (≤12 gestational weeks) and late (>12 gestational weeks) partial PM were studied. A total of 80 early and 20 late PMs (37 from 1981–90; 63 from 1991–98) were analyzed. Mean gestational ages were 9.6 weeks for early PMs and 14.8 weeks for late PMs. Early PM was more common in 1991–1998 (57/63, 90%) than in 1981–1990 (23/37, 62%). Pre-evacuation diagnosis of hydatidiform mole was achieved in only 4 early and 1 late PMs. There were no significant differences in histology between early and late PMs, except that villi were smaller in early PMs and there was extensive stromal fibrosis in late PMs. Ploidy was as follows: 70 of 80 early PMs and 19 of 20 late PMs were triploid, 5 early PMs were aneuploid, and 5 early and 1 late PM were diploid. None of 45 patients with early PM and 1 of 11 with late triploid PM developed persistent gestational trophoblastic disease. Early PM is now more prevalent than it was previously. This may be a result of greater awareness of the entity of PM, its increased recognition by pathologists and the widespread use of ultrasound in the diagnosis and management of intrauterine fetal death. The diagnosis of PM should be based on pathological examination, since most PMs still elude clinical detection. DNA ploidy analysis is useful in the evaluation of problem cases. The risk of persistent disease seems to be very low in the case of early PMs. Received: 6 December 1999 / Accepted: 1 March 2000     

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...     

Triploidy, partial mole and dispermy. An investigation of 12 cases

Twelve triploid abortuses were investigated to determine the origin of the additional haploid set and were retrospectively examined for the development of partial hydatidiform mole. Eight out of ten suitable triploids were diagnosed as partial mole. Dispermy was indicated as the cause of triploidy in 6 informative cases of which 3 were also partial moles. However, one diandric triploid had no features of partial mole. The problem of maternal cell contamination in triploids and the difficulty of diagnosing partial moles on pathological grounds alone are discussed.     

Anti-ovalbumin antibody binds to 3T3 cells and induces DNA synthesis

Rabbit anti-ovalbumin antibodies were found to bind to Swiss NIH 3T3 fibroblasts by indirect immunofluorescence, and to induce DNA synthesis when these cells were arrested in G0 phase of their replicating cycle (G0-S activity). The proof that these effects were related to the ovalbumin paratopes is based on the following arguments. Antibodies prepared by affinity chromatography from rabbits immunized in the presence or absence of complete Freund adjuvant, possessed the same specific activity. Immunoglobulins from ovalbumin-immunized rabbits were isolated on a protein A Sepharose column and then fractionated on insoluble ovalbumin; the retained fraction displayed G0-S activity and showed indirect immunofluorescence, whilst the non-retained fraction was inactive. Fluorescence was specifically quenched by ovalbumin and the G0-S activity recovered in the ovalbumin immune precipitate. (Fab')2 fragments had the same effects as the native immunoglobulins, but presented a moderate decrease in specific activity.     

检测FGFR3基因鉴别诊断先天性软骨发育不全

目的 建立一种基因水平上鉴别诊断先天性软骨发育不全的方法。方法 采用PCR—RFLP技术对1例临床确诊的ACH患者，1例临床怀疑为ACH患者的FGFR3基因第10外显子1138位核苷酸作突变型分析。结果 确诊的ACH患者1138核苷酸存在C→A的转换，而临床怀疑为ACH患者的1138核苷酸无任何改变。结论 检测FCFR3基因突变可从分子水平上鉴别诊断先天性软管发育不全，准确率达95％。     

Multiplex short tandem repeat DNA analysis confirms the accuracy of p57(KIP2) immunostaining in the diagnosis of complete hydatidiform mole

Detailed histopathologic examination remains to be the basis for the diagnosis of hydatidiform mole (HM). However, poor sampling, necrosis, and earlier uterine evacuation can lead to uncertainty in the diagnosis. Also, the criteria are subjective, resulting in considerable interobserver variability. The p57(KIP2) gene is paternally imprinted and maternally expressed, and the presence of its protein product serves as a surrogate marker for the nuclear maternal genome. Because a complete HM (CHM) is the only type of conceptus lacking a maternal contribution, p57(KIP2) immunostaining is correspondingly absent, whereas it is present in CHM mimics. Although analysis of DNA microsatellite polymorphisms is a reliable method for the diagnosis and classification of HM, it is not universally available. To assess the relative accuracy of p57(KIP2) immunostaining and molecular diagnosis by nuclear DNA microsatellite polymorphisms in discriminating CHM from its mimics, we analyzed archival tissue from 33 case patients (7 with a definitive diagnosis of CHM, 16 with a possible diagnosis of HM, and 10 with normal placentas) by both methods. Concordant results were obtained in all cases, and p57(KIP2) immunostaining accurately identified all cases of CHM from the groups with a definitive or possible diagnosis of HM. p57(KIP2) immunohistochemistry is a time- and cost-effective means of distinguishing CHM from its mimics in challenging cases.     

Differential diagnosis between thyroid follicular adenoma and carcinoma. Analytic morphometric approach

In this study some nuclear dimensional and analytical parameters were evaluated in order to distinguish follicular atypical adenoma from follicular carcinoma of the thyroid. Eighty nuclei from carcinomas, 80 from adenomas and 80 from normal thyroid were studied. Analytical parameters obtained by the nuclear shape study (by S.A.M. system) as well as dimensional parameters were submitted to univariate statistical analysis. On the ground of our results atypical adenoma could be considered as an intermediate aspect of a progressive change from benign to malignant even if they are closer to normal thyroid than to carcinoma.     

Accelerated expansion of antibody heterogeneity by complete Freund's adjuvant during the response to bacterial alpha-amylase.

Changes in the isoelectric focusing (IEF) spectra of specific antibodies were followed during the response of individual mice to bacterial alpha-amylase (B alpha A) in either incomplete or complete Freund's adjuvant (IFA or CFA). The response to a suboptimal dose of B alpha A was maximally enhanced by employing CFA at an optimal dose of Mycobacterium tuberculosis. Regardless of the strain difference in responsiveness to B alpha A between C3H/He (C3) and C57B1/6 (B6) mice, the enhancing effect of CFA was characterized by an accelerated expansion of IEF spectra and by the intensified stain of focused antibody, compared with the response of mice immunized with the same antigen dose in IFA. The manner and the rate of heterogeneity expansion during the enhanced antibody response to a low dose in CFA were quite similar to the strictly restricted expansion of spectra during a response of a high dose of B alpha A in IFA, although each mouse showed an individual banding pattern with a different degree of heterogeneity, depending on the antibody titre. Thus, CFA accelerated the expansion of IEF spectra during the response to B alpha A without affecting the general manner of sequential expansion of anti-B alpha A antibody heterogeneity.     

Hydatidiform mole and HLA. II. Compatibility between patient and conceptus

In 52 conceptuses with known genomic origin, the HLA types expressed on whole villi and/or stromal cell cultures were compared with the HLA types of the patients. No preference for either HLA compatibility or incompatibility was found for androgenetic and paternally derived triploid conceptuses as a whole. Heterozygous, androgenetic, conceptuses, however, showed a trend towards preferential incompatibility, which may be of importance for their apparent greater risk for trophoblastic tumour. HLA antibodies were found in 19.2% of the women, i.e. in the range reported for molar as well as non-molar pregnancies. Non-HLA antibodies reacting with lymphocytes of the spouse and/or cells from the conceptus were observed.     

Differential diagnosis between undifferentiated tumor and thymoma by electron microscopy and immunohistochemical labelling

This study of a particular case of tumor posed and resolved problems of differential diagnosis between an undifferentiated tumor and a thymoma by using electron microscopy in association with immunocytochemical methods. The first step was the distinction between an epithelial and a mesenchymal tumor, which was done by electron microscopy and immunofluorescence observation with anti-keratin antibody. The second step, a new approach to this problem, was the distinction between an epithelial tumor of thymic origin and another tumor located in the mediastinal lodge. A clear distinction was made by observation in immunofluorescence using anti-thymulin monoclonal antibody. This double approach permits differential diagnosis, excludes neoplasms of germ-cell origin, malignant lymphomas and leukemias, as well as mesenchymal tumors, and affirms the thymic origin of the tumor observed. A second type of cell observed in this tumor with a peculiar aspect, different from all types of epithelial cells observed in normal thymus, is discussed.     

Chloramphenicol-specific antibody: III. Differential antibody decay rates to separate determinants of one antigen

In rabbits, peak titres to repeated immunization with chloramphenicol bound to bovine γ-globulin (CAP—BGG) appear on the 4th to 7th day for the BGG part of the antigen, but not until the 9th to 12th day for CAP. Similarly the antibody to CAP declines in titre much more rapidly than the antibody to the BGG and 4–6 weeks later anti-CAP antibody is no longer detectable while the anti-BGG antibody is still found in high titre.