Assessment of cell proliferation in hydatidiform mole using monoclonal antibody MIB1 to Ki-67 antigen.

AIMS--To assess the role of Ki67 immunoreactivity in predicting the clinical progress of hydatidiform mole. METHODS--Tissue from 87 hydatidiform moles, 11 normal first trimester placentas, 11 normal term placentas and 17 spontaneous abortions were examined for expression of Ki67 antigen, using the monoclonal antibody MIB1. RESULTS--Ki67 immunoreactivity was significantly higher in the tissue from normal first trimester placentas than in that from normal term placentas and spontaneous abortions. Among the 87 patients with hydatidiform moles studied, 20 developed persistent gestational trophoblastic disease and required subsequent treatment. There was no statistically significant difference in the Ki67 index between the 20 patients who developed persistent disease and those who did not. CONCLUSION--Hydatidiform moles which give rise to persistent trophoblastic disease do not have a higher proliferative rate than those which do not. The Ki67 index is not useful for predicting the prognosis of molar pregnancies.     

Use of proliferation cell nuclear antigen immunoreactivity for distinguishing hydropic abortions from partial hydatidiform moles.

AIMS: To determine whether the expression of proliferating cell nuclear antigen (PCNA) in villous cytotrophoblast could distinguish between placental tissue from a hydropic abortion and that from a partial hydatidiform mole. METHODS: Tissue from 18 partial hydatidiform moles, 15 hydropic abortions, five normal first trimester placentas and five normal full term placentas were immunostained for expression of PCNA, using the monoclonal antibody PC10. RESULTS: PCNA immunoreactivity was very much higher in the cytotrophoblast of normal first trimester placentas than in normal term placentas. Villous tissue from partial hydatidiform moles showed, on average, less immunoreactivity for PCNA than did villous tissue from hydropic abortions. CONCLUSIONS: Immunostaining for PCNA is of no value for differentiating between partial hydatidiform moles and hydropic abortions. The findings indicate that trophoblastic proliferation or hyperplasia is not a feature of partial hydatidiform moles.     

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.     

A clinical, histopathological and flow cytometric study of 149 complete moles, 146 partial moles and 107 non-molar hydropic abortions

We have compared the clinical and histological features of 149 complete moles with 146 triploid partial moles and 107 diploid non-molar hydropic abortions initially registered as moles for human chorionic gonadotrophin (hCG) follow-up. Forty-one patients with complete moles, five with partial moles and one with hydropic abortion received chemotherapy for hCG elevations interpreted as persistent trophoblastic disease. Complete moles were aborted or were evacuated significantly earlier than partial moles (means of 12.1 and 15.4 weeks; P  <0.001) and hydropic abortions significantly earlier than complete moles (mean 10.7 weeks; P <0.005). The means of the highest recorded hCG were higher in complete moles (184 056 i.v.) than in partial moles (66 259 i.v.) and hydropic abortion (7942 i.v.). When hCG became normal without chemotherapy, this occurred earlier in patients with hydropic abortion than in those with partial moles (means of 46.7 days and 62.8 days; P <0.001) and earlier in partial moles than in complete moles (mean 78.3 days; P <0.005). The incidence of partial moles was comparable throughout fertile years but rose to 1.9 times the average after 40 years. Complete moles were commoner between 14 and 25 years and after 35 years, reaching 4.8 times the average after 40 years. Hydropic abortions were rare before 25 years and increased with age to 12 times the average after 40 years. Stromal karyorrhexis and shape of villi, before they become hydropic, discriminate well between complete and partial mole. Hydrops increased and vascularity decreased with molar age and the presence of non-hydropic villi or vessels did not discriminate between partial mole and the younger complete moles evacuated nowadays.     

Apoptosis in gestational trophoblastic disease is correlated with clinical outcome and Bcl-2 expression but not Bax expression.

Apoptosis has been found to play a crucial role in the pathogenesis and prognosis of many human diseases. The pathogenesis of gestational trophoblastic disease (GTD), which encompasses hydatidiform moles (HMs) and choriocarcinomas (CCAs), is not fully understood. Prognostic indicators of HM have also been scanty. In this study, we investigated apoptotic activity and the expression of two apoptosis regulatory genes, Bcl-2 and Bax, in an attempt to determine the role of apoptosis in GTD. Formalin-fixed paraffin-embedded tissue of 33 normal placentas, 14 spontaneous abortions, 14 partial moles, 34 complete moles, and eight CCAs were examined. Apoptotic activity was assessed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. Quantitative assessment of apoptotic index (AI) was calculated as a percentage of TUNEL-positive nuclei. Expression of Bcl-2 and Bax were assessed immunohistochemically. Extensive apoptosis was located in syncytiotrophoblasts, cytotrophoblasts, and villous stromal cells in all HM cases. Apoptosis was detected at a much lower level in spontaneous abortions and normal placentas. Moreover, in normal placentas, TUNEL positive nuclei were exclusively found in syncytiotrophoblasts. AIs were significantly different among various categories of trophoblastic lesions (P < .001) in an ascending order: normal placentas less than spontaneous abortions less than CCAs less than HMs. Furthermore, AIs of those cases that spontaneously regressed was statistically higher than those that developed persistent trophoblastic disease requiring chemotherapy. AIs of trophoblastic lesions in general inversely correlated with Bcl-2 expression (P < .001), but no significant correlation was found between AI and Bax expression (P > .5). We conclude that AI may be a useful prognostic marker for clinical progress of HMs. Bcl-2 expression is probably regulating apoptosis in normal placentas and GTD, whereas Bax expression is not. The difference in AI and Bcl-2 expression between non-molar placentas and HMs offers a potential adjunctive diagnostic tool to distinguish the two entities.     

Melanosis of the appendix: common in the paediatric age group

AIMS: The objective of this study was to assess apoptotic activity in gestational trophoblastic disease (GTD) and its prognostic value in hydatidiform mole (HM). METHODS AND RESULTS: Expression of the specific caspase cleavage site within cytokeratin 18 was assessed immunohistochemically using the monoclonal antibody M30 CytoDeath in 12 spontaneous abortions, 22 partial and 57 complete HM, eight choriocarcinoma (CCA) and 28 normal placentas. The M30 immunoreactivity occurred predominantly in the syncytiotrophoblasts. A significantly higher M30 index in HM and CCA was found when compared with normal placentas and spontaneous abortions (P < 0.001). The M30 index of those HM which spontaneously regressed was significantly higher than those HM which developed persistent disease requiring chemotherapy (P < 0.001). The M30 index correlated with another apoptotic index previously detected by TdT-mediated dUTP nick-end labelling (TUNEL) (P = 0.007) and the proliferation index assessed by the Ki67 antigen (P = 0.034). CONCLUSIONS: We conclude that apoptosis is important in the pathogenesis of GTD. Assessment of apoptotic activity in HM by the M30 index may be considered as an alternative prognostic indicator for predicting the clinical behaviour.     

Diagnosis of molar pregnancy and persistent trophoblastic disease by flow cytometry.

Histopathological assessment and flow cytometric analyses were carried out on 32 placentas (representative of each trimester) and 88 molar pregnancies. Three first trimester placentas were triploid, and the remaining 29 placentas were diploid. Of the 88 cases originally diagnosed as molar pregnancies, 26 were triploid (two complete moles, 20 partial moles, and four hydropic abortions); 59 were diploid (46 complete moles, 10 partial moles, three hydropic abortions); one was tetraploid (partial mole); and two were DNA aneuploid (one partial mole, one complete mole). A significantly increased hyperdiploid fraction (a measure of cell proliferation) was detected in diploid complete moles (p less than 0.0001) and cases of persistent trophoblastic disease (p less than 0.001) when compared with diploid placentas and diploid partial moles. All seven cases of established persistent trophoblastic disease, for which follow up was available, were diploid and showed high hyperdiploid fractions within the range for diploid complete moles. These findings suggest that flow cytometric DNA measurements may be an important aid in the diagnosis of molar pregnancy. The high degree of cell proliferation found in this study may explain the premalignant potential of complete hydatidiform moles.     

Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, Cyclin E, p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease.

The role of cell cycle protein expression in gestational trophoblastic disease is poorly understood. In this study we investigated the immunostaining patterns of G(1) restriction point and G(1)-S regulatory proteins E2F-1, Cdk2, cyclin E, p27(kip1), and the proliferation marker Ki-67 on routinely processed sections of 29 hydatidiform moles (10 partial moles and 19 complete moles, including 9 persistent moles), 7 choriocarcinomas, and 7 normal placentas. Ki-67 trophoblast staining decreased with increasing gestational age of the placenta, and showed maximal expression in gestational trophoblastic disease. Cyclin-dependent kinase activity, as reflected by Cdk2 expression patterns, also decreased with placental maturation. E2F-1 was uniquely expressed by trophoblasts of moles and choriocarcinoma. Cyclin E was maximally expressed by complete moles and choriocarcinomas, and showed an inverse relationship with the cyclin-dependent kinase inhibitor p27(kip1). Abnormal trophoblastic proliferations may be mediated through interactions of Cdk-2, E2F-1, cyclin E, and p27(kip1). Overexpression of cyclin E was associated with more aggressive forms of gestational trophoblastic disease. However, we did not find distinguishing features between complete moles that spontaneously resolved after evacuation and persistent moles that required chemotherapy. The different expression patterns of cyclin E and E2F-1 in partial and complete moles may be useful in distinguishing these two entities. Furthermore, loss of p27(kip1) in malignant trophoblast may represent a necessary step in the development of choriocarcinoma.     

p21WAF1/CIP1 expression in gestational trophoblastic disease: correlation with clinicopathological parameters, and Ki67 and p53 gene expression.

BACKGROUND: The p21WAF1/CIP1 gene mediates growth arrest by inhibiting G1 cyclin dependent kinases and has been considered as a downstream effector of the tumour suppressor gene p53. AIM: To analyse the role of p21WAF1/CIP1 in gestational trophoblastic disease. METHODS: The immunohistochemical expression of p21WAF1/CIP1 gene was measured in 33 placentas, 28 partial hydatidiform moles, 54 complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1) immunoreactivity as well as clinical progress. RESULTS: p21WAF1/CIP1 immunoreactivity was found predominantly in the nuclei of the syncytiotrophoblasts. p21WAF1/CIP1 protein expression correlated with gestational age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89). Complete hydatidiform moles and choriocarcinomas had a significantly higher p21WAF1/CIP1 expression compared with normal placentas and partial hydatidiform moles (p < 0.001); there was no difference between placentas and partial hydatidiform moles. No correlation between p21WAF1/CIP1 expression and either the proliferation (Ki67) index (p = 0.34) or p53 protein accumulation (p = 0.68) was demonstrated. There was no significant difference (p > 0.05) in p21WAF1/CIP1 expression between the 17 patients who developed persistent gestational trophoblastic disease and those who did not. CONCLUSIONS: This study suggests that p21WAF1/CIP1 expression in trophoblastic disease may be induced by a p53 independent pathway. The proliferative activity of gestational trophoblastic diseases might not be determined solely by the control of the cell cycle operated by p21WAF1/CIP1. p21WAF1/CIP1 expression is not an accurate prognostic indicator of gestational trophoblastic disease.     

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.     

Do AgNOR counts reflect cellular ploidy or cellular proliferation? A study of trophoblastic tissue

There is considerable debate as to whether AgNOR counts reflect cellular ploidy or cellular proliferation. Trophoblastic tissue from hydropic abortions and from hydatidiform moles offers an excellent model for analysing this problem. Thus, complete moles show considerable cell proliferation but are diploid, whilst partial moles show markedly less cell proliferation but are triploid: hydropic abortuses are diploid and show no cellular proliferation. AgNOR counts in villous cytotrophoblastic cells from hydropic abortions and from complete hydatidiform moles are similar, but those in partial hydatidiform moles are 50 per cent higher than in either hydropic abortions or complete moles. Thus, in non-neoplastic trophoblastic tissue AgNOR counts are clearly a reflection of ploidy rather than of cell proliferation.     

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.     

Hydatidiform moles. Application of flow cytometry in diagnosis

Hydropic chorionic villi are found in hydropic abortuses, partial hydatidiform moles (PM), and complete hydatidiform moles. Partial and complete moles have the potential for persistent trophoblastic disease. The vast majority of partial moles are triploid and generally follow a benign clinical course. Complete moles are diploid and distant metastasis and choriocarcinoma may develop. The authors determined the nuclear ploidy by flow cytometry of 31 placentas, 19 of which appeared hydropic either on obstetric ultrasonography or gross examination. Of ten complete moles classified by histologic criteria, ten were diploid, whereas five of seven histologically classified PM were triploid. The remaining two cases classified as PM were diploid; one most likely represented a regressing complete mole; the other a hydropic abortus. All 14 control placentas were diploid. In all cases in which karyotypic analysis was performed, the flow cytometric determination of ploidy was confirmed. It was concluded that DNA flow cytometric analysis is a rapid, accurate, and cost-effective means for assaying nuclear ploidy in these tissues, and as such, offers an informative supplement to the histological interpretation of hydropic placentas.     

Telomerase activity in gestational trophoblastic disease

AIMS: To investigate the pattern of telomerase activity in hydatidiform mole as compared with normal placenta and choriocarcinoma, and to determine the prognostic significance of telomerase activity in hydatidiform mole. METHODS: Telomerase activity in 35 cases of hydatidiform mole, 35 normal placentas, one choriocarcinoma sample, and two choriocarcinoma cell lines (JAR, JEG3) was determined using the sensitive polymerase chain reaction based telomeric repeat amplification protocol (TRAP) assay. Two cases of breast carcinoma and two cases of ovarian carcinoma were also included as positive controls in the telomerase assay. RESULTS: Telomerase activity was detected in 11 of 30 early placentas (36.7%), one of five term placentas (20%), five of 27 hydatidiform moles which regressed spontaneously (18.5%), and six of eight hydatidiform moles which developed persistent trophoblastic disease (75%) (including three which developed metastases). Hydatidiform moles which subsequently developed persistent disease, especially those which metastasised, were more likely to express telomerase activity (p < 0.01). However, there was no significant difference in the frequency of telomerase activity between early placentas and hydatidiform mole. Strong telomerase activity was observed in choriocarcinoma tissue, choriocarcinoma cell lines, and ovarian and breast carcinomas. CONCLUSIONS: Telomerase activation occurs in hydatidiform mole with a similar incidence to early normal placentas. This supports the concept that hydatidiform mole is essentially an abnormal conceptus. There is an association between telomerase activation and the development of persistent trophoblastic disease. Further study is warrant to confirm the prognostic significance of telomerase activity in hydatidiform mole.     

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.     

Choriocarcinoma following a partial hydatidiform mole: a case report.

Hydatidiform moles are classified as partial or complete by histologic criteria (Am J Obstet Gynecol 131:665-671, 1978 and Am J Obstet Gynecol 132:20-27, 1978). While persistent gestational trophoblastic tumors follow both types, there remains controversy as to whether the malignant extreme of gestational trophoblastic tumors, choriocarcinoma, can follow a partial hydatidiform mole (Am J Obstet Gynecol 127:167-170, 1977 and Arch Gynecol 234:161-166, 1984). In this instance, a 37-year-old woman presented with a partial hydatidiform mole that persisted and was treated with one course of chemotherapy. She attained a remission for 10 months, when a routine follow-up examination revealed an asymptomatic rise in serum beta-human chorionic gonadotropin from baseline to 14,600 mIU/mL. Dilatation and curettage revealed abundant avillous cytotrophoblast and syncytiotrophoblast with marked atypia, diagnostic of choriocarcinoma. Flow cytometry of paraffin blocks of both specimens showed the partial hydatidiform mole to be triploid and the choriocarcinoma diploid. The patient had no evidence of metastatic disease and was successfully treated with multiple-agent chemotherapy.     

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。     

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.     

Sister chromatid exchange and chromosome breakage in complete hydatidiform moles.

Women with complete hydatidiform moles (CHM) are at a 10% risk for developing persistent trophoblastic disease or choriocarcinoma. We studied sister chromatid exchange (SCE) as a prognostic indicator for malignancy in peripheral blood lymphocytes (PBL) from women with CHM and their husbands, but found no differences from normal control couples. SCE levels in cultured tissue derived from 11 CHM (avg. 7.9) and 2 choriocarcinomas (avg. 6.8) were not significantly different from those of 8 normal skin fibroblast cultures (avg. 7.8). These same tissues were then examined for chromosome breakage which was significantly higher for CHM (0.48/cell) and choriocarcinoma (0.87/cell) than normal fibroblasts (0.33/cell). Chromosome breaks occurred at 50-60% known fragile sites and at 50-55% of cancer breakpoints. Whereas SCE was only associated with 13% of breaks in the three tissues, half of these were at known fragile sites. Our results suggest that SCE is not an indicator of malignancy in PBL or cultured cells from CHM or choriocarcinoma and that the level of SCE is not elevated in CHM or choriocarcinoma. However, our results confirm the increased breakage seen in the latter two tissues which may represent general DNA instability predisposing to choriocarcinoma and its accompanying chromosomal rearrangements.     

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.