Prevalence of oral HPV infection in cervical HPV positive women and their sexual partners.

PURPOSE: Human papillomavirus (HPV) infection represents the primary cause of anogenital premalignant and malignant disease. Regarding the high prevalence of cervical HPV infection and the increasing incidence of HPV associated oropharyngeal cancer in recent years, a significant viral transmission from the cervical to the oral site, possibly depending on the sexual behavior must be considered. The present study aims to determine the prevalence of oral HPV infection in cervical HPV positive and negative women and their sexual partners. METHODS: Cervical HPV positive and negative women and their sexual partners took part in the study. Cervical smears, oral smears and mouthwashes were taken from women attending gynecological outpatient clinics in two different institutions. Further, oral smears as well as mouthwashes of their sexual partners were obtained whenever possible. HPV genotyping was performed using the Cobas® polymerase chain reaction and nucleic acid hybridization assay for the detection of 14 high-risk HPV types. In addition, all participants were invited to complete a personal questionnaire. RESULTS: 144 HPV positive and 77 HPV negative women and altogether 157 sexual partners took part in the study. Age, sexual behaviour, medication, smoking and alcohol consumption were distributed equally in both groups. Cervical HPV positive women had a significantly higher number of sexual partners. One woman with a HPV positive cervical smear and one partner of a woman with a HPV positive cervical smear showed an oral HPV infection. No oral HPV infections were detected in the HPV negative control group. The overall incidence of oral HPV infection was 0.5%, the incidence of oral HPV infection in women with a positive cervical smear was 0.7%. CONCLUSION: The data demonstrate that the overall risk of an oral HPV infection is low. HPV transmission to the oropharynx by autoinoculation or oral-genital contact constitute a rare and unlikely event.

Expression pattern and prognostic potential of histamine receptors in epithelial ovarian cancer.

PURPOSE: Despite recent advances in the treatment of ovarian cancer (OC), long-term remissions remain scarce. For a targeted approach, prognostic markers are indispensable for predicting survival and treatment response. Given their association with multiple hallmarks of cancer, histamine receptors (HR) are emerging as promising candidates. Here, we investigate their expression pattern and prognostic value in OC. METHODS: Specimens of 156 epithelial OC patients were collected during cytoreductive surgery at the Department of Obstetrics and Gynecology, LMU, between 1990 and 2002 and combined in a tissue microarray. Immunohistochemical staining of the HR H1, H2, H3 and H4 was quantified by an immunoreactive score and linked with clinico-pathological data by Spearman's correlation. Via ROC curve analysis, optimal cut-off values for potential prognostic markers were defined. Overall survival (OS) was visualized in Kaplan-Maier curves and significances determined by log-rank testing. A Cox regression model was applied for multivariate analysis. RESULTS: HR H3 and H4 expression was restricted to the cytosol of OC cells, while H1 was also present in the nucleus. A significant association between HR H1, H3 and H4 expression with several clinico-pathological parameters was revealed. In addition, HR H1 and H3 expression correlated positively, HR H4 expression negatively with OS. In addition, HR H3 was identified as independent prognostic marker for OS. HR H2 expression had no prognostic value. CONCLUSIONS: HR H1, H3 and H4 could serve as potential predictors for OS of OC patients. Further research is warranted to elucidate their pathophysiologic role and their predictive and therapeutic potential in OC.

Characterization and prognostic impact of ACTBL2-positive tumor-infiltrating leukocytes in epithelial ovarian cancer.

Actin beta-like 2 (ACTBL2) was recently identified as a new mediator of migration in ovarian cancer cells. Yet, its impact on tumor-infiltrating and thus migrating leukocytes (TILs) remains to date unknown. This study characterizes the subset of ACTBL2-expressing TILs in epithelial ovarian cancer (EOC) and elucidates their prognostic influence on the overall survival of EOC patients with special regard to different histological subtypes. Comprehensive immunohistochemical analyses of Tissue-Microarrays of 156 ovarian cancer patients revealed, that a tumor infiltration by ACTBL2-positive leukocytes was significantly associated with an improved overall survival (OS) (61.2 vs. 34.4 months; p = 0.006) and was identified as an independent prognostic factor (HR = 0.556; p = 0.038). This significant survival benefit was particularly evident in patients with low-grade serous carcinoma (OS: median not reached vs. 15.6 months, p < 0.001; HR = 0.058, p = 0.018). In the present cohort, ACTBL2-positive TILs were mainly composed of CD44-positive cytotoxic T-cells (CD8+) and macrophages (CD68+), as depicted by double-immunofluorescence and various immunohistochemical serial staining. Our results provide significant evidence of the prognostic impact and cellular composition of ACTBL2-expressing TILs in EOC. Complementary studies are required to analyze the underlying molecular mechanisms of ACTBL2 as a marker for activated migrating leukocytes and to further characterize its immunological impact on ovarian carcinogenesis.

Aberrant expression of corticotropin-releasing hormone in pre-eclampsia induces expression of FasL in maternal macrophages and extravillous trophoblast apoptosis.

Corticotropin-releasing hormone (CRH) and its receptors are expressed in human placenta. Recently, the impaired function of this system has been associated with a number of complications of pregnancy, including pre-eclampsia. The aim of the study was to test the hypothesis that CRH participates in the pathophysiology of pre-eclampsia through the induction of macrophage-mediated apoptosis of extravillous trophoblasts (EVTs). We found that the expression of CRH was increased in the EVT of the placental bed biopsy specimens from pre-eclamptic pregnancies (1.8-fold increase; P < 0.05). In addition, significantly larger numbers of apoptotic EVT were detected in pre-eclamptic placentas compared with normal ones (P < 0.05), and only in pre-eclamptic placentas, decidual macrophages were found to be Fas ligand (FasL)-positive. In vitro studies on the effect of CRH on human macrophages suggested that CRH induced the expression of the FasL protein in human macrophages and potentiated their ability to induce the apoptosis of a Fas-expressing EVT-based hybridoma cell line in co-cultures. These findings demonstrate a possible mechanism by which the aberrant expression of CRH in pre-eclampsia may activate the FasL-positive decidual macrophages, impair the physiological turnover of EVT and eventually disturb placentation.

Effects of phytoestrogen extracts isolated from flax on hormone production of trophoblast tumour cells Jeg 3 and BeWo.

UNLABELLED: AIM AND SETTING: To test the effects of crude extracts from flax (Linum usitatissimum) on progesterone and estradiol and ERα and ß/PR production in choriocarcinoma cell lines Jeg 3 and BeWo. Tumor trophoblast cells (Jeg 3 and BeWo) were incubated in the presence of different concentrations of the flax crude extracts. Estradiol and progesterone production was measured. Estrogen receptor α and ß as well as progesterone receptor expressions were also assessed. RESULTS: In Jeg 3 cells, progesterone production was downregulated by flax root and leaves extract, while in BeWo cells only flax root extract did manage to downregulate progesterone production. ERß expression was significantly downregulated by flax root and flax leaves extract in both cell lines; on the contrary, ERα expression was increased by flax leaves extract in BeWo cells. PR expression was downregulated by flax leaves extract in Jeg 3 and by flax root extract in BeWo cells. CONCLUSION: Flax extracts derived from leaves and especially from roots can modify progesterone and possibly estradiol production, while at the same time they seem to alter ERß expression. Further studies on animal models and adequately designed retrospective epidemiological studies are imperative to clarify this role upon progesterone.

Yolk sac macrophage progenitors traffic to the embryo during defined stages of development.

Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal. However, the route and characteristics of YS macrophage trafficking during embryogenesis are incompletely understood. Here we show the early migration dynamics of YS-derived macrophage progenitors in vivo using fate mapping and intravital microscopy. From embryonic day 8.5 (E8.5) CX3CR1+ pre-macrophages are present in the mouse YS where they rapidly proliferate and gain access to the bloodstream to migrate towards the embryo. Trafficking of pre-macrophages and their progenitors from the YS to tissues peaks around E10.5, dramatically decreases towards E12.5 and is no longer evident from E14.5 onwards. Thus, YS progenitors use the vascular system during a restricted time window of embryogenesis to invade the growing fetus. These findings close an important gap in our understanding of the development of the innate immune system.

Author Correction: Yolk sac macrophage progenitors traffic to the embryo during defined stages of development.

This article contains errors in Figs. 5 and 6, for which we apologize. In Fig. 5f, the image 'E12.5 tail' was inadvertently replaced with a duplicate of the image 'E12.5 trunk' from the same panel. In Figure 6d, the image 'E9.5/OH-TAM E8.5, embryo' was inadvertently replaced with a duplicate of the image 'E10.5/ OH-TAM E8.5, embryo' from Fig. 6b. The corrected versions of these figures appear in the Author Correction associated with this Article.

Expression of galectin-1, -3 (gal-1, gal-3) and the Thomsen-Friedenreich (TF) antigen in normal, IUGR, preeclamptic and HELLP placentas.

BACKGROUND: Galectin-1 (gal-1) and galectin-3 (gal-3), which are members of the mammalian beta-galactoside-binding proteins, recognise preferentially (Galbeta1-4GlcNAc) sequences of several cell surface oligosaccharides. In addition, gal-1 also binds to the Thomsen-Friedenreich (TF) antigen (Galbeta1-3GalNAc-). MATERIALS AND METHODS: Slides of frozen and paraffin-embedded placental tissue of patients with fetal intrauterine growth retardation (IUGR), preeclampsia, haemolysis, elevated liver enzymes, low platelets (HELLP) and normal term placentas were incubated with monoclonal and polyclonal antibodies against gal-1, gal-3 and TF. Staining reaction was performed with the avidin-biotinylated peroxidase complex (ABC) reagent. The intensity of the immunohistochemical reaction on the slides was analysed using a semi-quantitative score. The identity of galectin-expressing cells was analysed by using a double immunofluorescence method. RESULTS: We demonstrated immunohistochemically that the expression of gal-1 and gal-3 on the extravillous trophoblast (EVT) is significantly up-regulated in preeclamptic and HELLP placentas and unchanged compared with normal controls in IUGR placentas. The expression of the TF antigen is significantly up-regulated in IUGR and preeclamptic extravillous trophoblast cells and unchanged in HELLP placentas compared with normal controls. In addition, the expression of gal-1 is significantly up-regulated in the decidual tissue of preeclamptic placentas and in the villous trophoblast tissue of HELLP placentas. CONCLUSION: Our data showed that gal-1, gal-3 and TF were up-regulated on the membrane of EVT in preeclamptic placentas. In addition, the expression of gal-1 is significantly up-regulated in decidual tissue of preeclamptic placentas and villous trophoblast tissue of HELLP placentas. Taking into consideration the results of this study, we speculate that expression of both galectins and TF on the membrane of preeclamptic EVT and up-regulation of gal-1 in preeclamptic decidual cells may at least in part compensate for the apoptotic effects of maternal immune cells.

Expression of the pantumour Thomsen-Friedenreich antigen in the human placenta with the diagnosis of hydatidiform mole.

BACKGROUND: The Thomsen-Friedenreich (TF) antigen (or, more precisely, epitope, Galbeta1-3GalNAc) has long been known as a pancarcinoma antigen. Specific carrier proteins of the TF-antigen are the mucins, in particular Mucin 1. Here, we present our results of immunohistochemical identification of this carbohydrate antigen in human placenta. MATERIALS AND METHODS: Paraffin-embedded placental and decidual tissues from patients with the diagnosis hydatidiform mole were incubated with different monoclonal antibodies directed against TF-epitope (CD 176, IgM) and against Mucin 1 (CD 227, IgG). RESULTS: No expression of the TF-antigen or of Mucin 1 (Muc 1) was found in the decidual tissues, but the samples of chorionic tissues were TF- and Muc 1-antigen positive. As positive control, placental samples of the first trimester were investigated. CONCLUSION: A disorder of the extravillous trophoblast cells is present in hydatidiform mole.

Maternal serum corticotropin-releasing hormone and ACTH levels as predictive markers of premature labor.

OBJECTIVE: To investigate whether corticotropin-releasing hormone (CRH) and corticotropin (ACTH) plasma concentrations in women diagnosed with preterm labor are of potential clinical value in the assessment of the risk of preterm birth. METHOD: Plasma samples of 79 women diagnosed with preterm labor were used in this study. Samples were divided into three groups based on the week of gestation (24th-28th, 29th-32nd, 33rd-37th). CRH and ACTH values were determined by ELISA. RESULT: Mean maternal peripheral plasma values of CRH and ACTH were significantly higher (p<0.001) in women who were initially diagnosed with preterm labor and finally delivered a preterm birth, compared to women with the same diagnosis but with term birth. CONCLUSION: CRH and ACTH serum levels in women diagnosed with preterm labor could be used as predictors for the timing of parturition.

Expression of inhibin/activin subunits alpha (-alpha), betaA (-betaA), and betaB (-betaB) in placental tissue of normal, preeclamptic, and HELLP pregnancies.

During human pregnancy the placenta produces a variety of proteins for the establishment of the fetoplacental unit, including inhibins and activins. Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB). Aims of the present study were (a) the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and (b) the assessment of a combined expression of inhibin-alpha- and both beta-subunits (betaA-and betaB-subunits) using double immunofluorescence technique. A significant lower expression of the inhibin-alpha subunit in preeclamptic and HELLP placental tissue compared to normal pregnancies was observed, while the inhibin-alpha immunostaining was significantly upregulated in syncytotrophoblast. Additionally, we demonstrated a significant down-regulation of inhibin-betaB subunit in extravillous trophoblast cells between normal and preeclamptic compared to HELLP placental tissue, while inhibin-betaA-subunit was significantly higher in preeclamptic syncytotrophoblast cells. A colocalization of inhibin-alpha and the beta-subunits could be demonstrated, suggesting a production and secretion of intact inhibin A and inhibin B. Therefore, inhibin A and activin A might be useful markers in preeclampsia. Valuable parameters in HELLP syndrome could be inhibin A, rather than inhibin B, and activin B. Furthermore, the lower betaB-subunit production in extravillous trophoblast cells demonstrates that this subunit might have an important role in the pathogenesis of HELLP syndrome. Additionally, the higher production of the betaA-subunit in syncytotrophoblast cells suggest a higher production of activin A rather than inhibin A in preeclampsia that might be utilized as a marker of placental function.

RXRα is upregulated in first trimester endometrial glands of spontaneous abortions unlike LXR and PPARγ.

Nuclear receptors are necessary for uterine invasion of the trophoblast and therefore important for maintaining a viable pregnancy. The aim of this study was to investigate the expression pattern and frequency of LXR, PPARγ and RXRα under physiological circumstances and in spontaneous abortions in endometrial glands and decidual tissue cells. A total of 28 (14 physiologic pregnancies/14 spontaneous abortion) human pregnancies in first trimester were analysed for expression of the nuclear receptors LXR, RXRα and PPARγ. Expression changes were evaluated by immunohistochemistry in decidual tissue and endometrial glands of the decidua. RXRα expression was up-regulated in the endometrial glands of spontaneous abortion (P<0.015). Similar up regulation of RXRα was found in decidual tissue (P<0.05). LXR and PPARγ expression was unchanged in spontaneous abortion. Via Correlation analysis we found a trend to positive correlation of LXR and PPARγ (Spearman correlation coefficient r=0.56 P=0.07) in endometrial glands. In decidual tissue, we found significant negative correlation in the control group, for the combination of RXRα and PPARγ (Spearman correlation coefficient r=0.913, P=0.03). Our data show that RXRα expression is increased in miscarriage in endometrial glands and correlation analysis showed that negative correlation between RXRα and PPARγ disappears in miscarriage. This shift is supposable responsible for the loss of regular function in trophoblast and embryonic tissue.

Disseminated and circulating tumor cells in bone marrow and blood of breast cancer patients: properties, enrichment, and potential targets.

INTRODUCTION: From the early days of pathology back in the nineteenth century until now, there has been an ongoing search for the missing link between solid tumors such as breast cancer and distant metastases, which sometimes occur many years after removal of the primary tumor. The "seed and soil" theory hypothesizes the early dissemination of occult tumor cells into blood or bone marrow, which can persist in a dormant state for a long time and then become precursors of metastases in distant organs which offer appropriate conditions. METHOD: Advances in immunocytochemical methods have enabled the enrichment and visualization of those disseminated tumor cells in bone marrow (DTC-BM) or circulating tumor cells (CTC) in blood. Many studies could demonstrate prognostic significance of the detection of DTC-BM or CTC in different stages of breast cancer. CONCLUSION: Further characterization of those cells by immunocytochemical stainings, fluorescence in situ hybridizations, or PCR-based molecular methods will help to understand the biology of tumor cell dissemination and metastasis formation, as well as to define potential drug targets.

Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors.

PURPOSE: We studied the prognostic and predictive value of immunohistochemically detected occult tumor cells (OTCs) in lymph nodes and bone marrow aspirates obtained from node-negative breast cancer patients. All were classified as distant metastases-free using conventional staging methods. PATIENTS AND METHODS: A total of 484 patients with pT1-2N0M0 breast cancer and 70 with pT1-2N1M0 breast cancer and a single affected lymph node participated in our trial. Ipsilateral axillary lymph nodes and intraoperatively aspirated bone marrow were examined. All samples were examined for OTCs using monoclonal antibodies to cytokeratins 8, 18, 19. Immunohistological findings were correlated with other prognostic factors. The mean follow-up was 54 +/- 24 months. RESULTS: OTCs were detected in 180 (37.2%) of 484 pT1-2N0M0 patients: in the bone marrow of 126 patients (26.0%), in the lymph nodes of 31 patients (6.4%), and in bone marrow and lymph nodes of 23 (4.8%) patients. Of the 70 patients with pT1-2N1MO breast cancer and a single involved lymph node, OTCs were identified in the bone marrow of 26 (37.1%). The ability to detect tumor cells increased with the following tumor features: larger size, poor differentiation, and higher proliferation. Tumors of patients with OTCs more frequently demonstrated lymph node invasion, blood vessel invasion, higher urokinase-type plasminogen activator levels, and increased PAI-1 concentrations. Patients with detected OTCs showed reduced disease-free survival (DFS) and overall survival (OAS) rates that were comparable to those observed in patients who had one positive lymph node. Multivariate analysis of prognostic factors revealed that OTCs, histological grading, and tumor size are significant predictors of DFS; OTCs and grading of OAS. CONCLUSION: OTCs detected by simultaneous immunohistochemical analysis of axillary lymph nodes and bone marrow demonstrate independent metastatic pathways. Although OTCs were significantly more frequent in patients with other unfavorable prognostic factors, they were confirmed as an independent prognostic factor for pT1-2N0M0, R0 breast cancer patients.

Expression of glycodelin A in decidual tissue of preeclamptic, HELLP and intrauterine growth-restricted pregnancies.

During pregnancy, the placenta produces a variety of proteins that are responsible for the establishment of the foeto-maternal tolerance and circulation. The aim of this study was to investigate the expression of glycodelin A (formerly named PP14) in decidual tissue of placentas with intrauterine growth restriction (IUGR), preeclamptic patients, hemolysis, elevated liver, low-platelet (HELLP) patients and normal decidual tissue. Slides of paraffin-embedded decidual tissue of patients with IUGR, preeclamptic patients, HELLP patients and normal-term placentas were incubated with either polyclonal or monoclonal antibodies against glycodelin A. Staining reaction was performed with the ABC reagent. Intensity of immunohistochemical reaction on the slides was analysed using a semi-quantitative score. In addition, expression of glycodelin mRNA was analysed by in situ hybridisation. Expression of glycodelin A was significantly reduced in decidual cells of placentas with IUGR and HELLP, as investigated with both monoclonal and polyclonal antibodies and in situ hybridisation. However, preeclamptic decidual tissue showed no significantly different expression of intensity of glycodelin mRNA compared with normal placental tissue controls. A reduced expression of glycodelin A by decidual cells seems to be related to IUGR and HELLP. Therefore, glycodelin A might play an important role in the pathogeneses of these diseases.

Expression of the Thomsen-Friedenreich (TF) tumor antigen in human abort placentas.

The Thomsen-Friedenreich antigen (TF), or more precisely epitope, has been known as a pancarcinoma antigen. It consists of galactose-beta1-3-N-acetylgalactose. We have already described the expression of TF in the normal placenta. TF is expressed by the syncytium and by extravillous trophoblast cells. In this study, we investigated the expression of TF in the abort placenta. Frozen samples of human abort placentas (12 placentas), obtained from the first and second trimesters of pregnancy and, for comparison, samples of normal placentas (17 placentas) from the first, second and third trimesters of pregnancy, were used. Expression of TF was investigated by immunohistochemical methods. For identification of TF-positive cells in abort placentas, immunofluorescence methods were used. Evaluation of simple and double immunofluorescence was performed on a laser scanning microscope. Furthermore, we isolated trophoblast cells from first and third trimester placentas and evaluated cytokeratin 7 and Muc1 expression by immunofluorescence methods. We observed expression of TF antigen in the syncytiotrophoblasts layer of the placenta in all three trimesters of pregnancy in normal and abort placentas evaluated by immunohistochemical methods. There was no expression of TF antigen in the decidua of abort placentas. Immunofluorescence double staining of TF antigen and cytokeratin 7 showed reduced expression of both antigens in the abort decidua and co-expression of both antigens in the syncytiotrophoblast layer of normal and abort placentas. TF expression in the syncytiotrophoblast was reduced in abort placentas. In the isolated trophoblast cells, no TF expression was found, however, Muc1 expression was visualized. Expression of TF antigen was reduced in the first and second trimester abort decidua compared to the normal decidua during the same time of pregnancy. TF antigen was restricted to the syncytiotrophoblast and extravillous trophoblast cells in the decidua. Abort placentas expressed TF antigen on the syncytiotrophoblast layer, but with lower intensity compared to normal placentas. We found a significantly reduced co-expression of TF antigen and cytokeratin 7 in the decidua of abort placentas. These data suggested a reduction of extravillous trophoblast cells in the decidua of abort placentas. In addition, we found higher numbers of CD45-positive cells in the abort decidua compared to normal placentas.

Normal and malignant human endometrium express immunohistochemically estrogen receptor alpha (ER-alpha), estrogen receptor beta (ER-beta) and progesterone receptor (PR).

Human endometrium expresses estrogen (ER) and progesterone (PR) receptors, which are related to autocrine and paracrine processes that respond to estrogen and progesterone. The ER and PR expression and distribution pattern may play an important role in endometrial function and pathogenesis. The aim of this study was to evaluate the distribution pattern of ER-alpha, ER-beta and PR in normal (n=15) and malignant (n=11) human endometrial tissue. Commercially available monoclonal antibodies against ER-alpha, ER-beta and PR were used. The distribution of the steroid receptors was evaluated using the IRS-score and the Mann-Whitney rank-sum test was used to compare the means. Correlation was assessed with the Spearman factor and linear regression analysis. ER-alpha, ER-beta and PR declined significantly (p <0.05) in normal glandular epithelium from proliferative to late secretory phase, although the staining intensity of ER-beta was lower than that of ER-alpha. ER-alpha, ER-beta and PR were also expressed in malignant endometrial tissue. A significant correlation by regression analysis of ER-alpha and ER-beta was demonstrated, showing a dependence in the expression of these steroid receptors. The ER-alpha/ER-beta ratio decreased significantly from normal to malignant endometrial tissue (p<0.05), while the ER-beta/ER-alpha ratio showed statistical differences within normal endometrial tissue. These results showed the presence of steroid receptors in normal and malignant human endometrium, indicating a significant role in endometrial physiology and malignant transformation.

Expression of inhibin/activin subunits, sialyl-lewis A (CA 19-9, sLea) and sialyl-Lewis X (sLex) carbohydrate antigens in a hydatidiform mole with persistent polymorphic trophoblastic hyperplasia.

UNLABELLED: The persistence of polymorphic trophoblastic hyperplasia in a hydatidiform mole is an extremely rare condition. Its early diagnosis is essential since such cases can transform into invasive tumours. MATERIALS AND METHODS: The paraffin-embedded biopsies were routinely stained with HE. Immunohistochemical staining reactions were performed with monoclonal antibodies against inhibin-alpha, inhibin-betaA and inhibin-betaB subunits. Additional immunohistochemical reaction was performed with, Sialyl-Lewis A and Sialyl-Lewis X and glycodelin. RESULTS: Large villi and hydatidiform villi with ranging syncyctio- and cytotrophoblasts were seen. Intervillous proliferating trophoblasts showed cell- and nuclear polymorphy with invasion of the myometrium wall. The immunohistochemistry exhibited strong positivity for inhibin-alpha, inhibin-betaA and inhibin-betaB subunits in trophoblastic tissue, while the decidua was negative. Sialyl-Lewis A and Sialyl-Lewis X showed no or minimal focal immunohistochemical reaction. CONCLUSION: A complete hydatidiform mole with hyperplasia and proliferation presents a high risk of developing a persistent (eventually metastatic) trophoblastic disorder and, in up to 15% of the cases, an invasive mole. In 2.5% of the cases it can transform into a choriocarcinoma. Since the inhibin/activin subunits reacted positively with trophoblastic tissue, they might be a useful diagnostic marker for hydatidiform mole with persistence of polymorphic trophoblastic hyperplasia.

Flax-seed extracts with phytoestrogenic effects on a hormone receptor-positive tumour cell line.

UNLABELLED: The higher soy intake in the Asian population compared to Europeans is believed to be an essential factor for the lower incidence of hormone-dependent tumours in Asia. It has already been shown that soya beans, with their ingredients genistein and daidzein from the isoflavonoid group, have protective effects on hormone-caused diseases. Lignans are another, less investigated, group of phytoestrogens. The aim of this study was to investigate the effects of flax-seed, which is typically found in Northern European diets, on the proliferation and hormone production of an estrogen receptor (ER)-positive trophoblast tumour cell line. MATERIALS AND METHODS: Trophoblast tumour cells of the cell line Jeg3 were incubated with 2 different concentrations of the isolated crude extract of flax-seed and 7 chemically partitioned extract fractions. Untreated cells were used as controls. After 48 h of stimulation, cell proliferation was measured using the BrdU method. The concentrations of hCG and progesterone produced by the trophoblast tumour cells were measured 48 h after stimulation. Extract fractions with antiproliferative effects in the BrdU- test were analysed by HPLC-MS. RESULTS: Our study showed an inhibitory influence of some of the isolated flax-seed fractions on the Jeg3 tumour cells. Proliferation of the Jeg3 cells was decreased by flax-seed fractions I, V, VI and VII in a dose-dependent manner. Inhibition of hCG production by flax-seed extracts III, V, VI and VII was also dose-dependent. Extract fractions V and VI decreased the production of progesterone by 58% to 86%. Some extract fractions showed a stimulating effect on hormone production and cell proliferation. HPLC-MS analysis showed the presence of matairesinol and biochanin A in flax-seed fraction VI. DISCUSSION: Flax-seed seems to have similar inhibitory effects to soya on hormone production and proliferation of hormone-sensitive tumour cells. Our results showed a dose-dependent inhibition by isolated flax-seed extracts on the Jeg3 cell line. Matairesinol and biochanin A seem to be useful candidates for extended tests on other tumour cell lines and normal tissues to evaluate the potential benefit of a lignan-containing therapy in hormone-dependent diseases.

Galectin-13/PP-13 expression in term placentas of gestational diabetes mellitus pregnancies.

INTRODUCTION: Gestational diabetes mellitus (GDM) is an increasing harm in pregnancy. Inflammatory processes in the placenta seem to have an influence on pathogenesis besides known factors like maternal BMI. Galectin-13 (gal-13) is an immunoregulatory protein, which is suspected to play a role in development of GDM in the placenta. METHODS: A total of 40 placentas were obtained from women treated for gestational diabetes mellitus. Placental tissue for control group was obtained from 40 women with normal pregnancy. We investigated the protein expression of gal-13 in term placentas with immunohistochemistry and immunofluorescence. Immunohistochemical staining was analyzed with the semi-quantified IRS score. Gal-13 serum levels were performed with ELISA on a total of 20 probes from women with GDM and healthy control pregnancies in the third trimester. RESULTS: Gal-13 was found in syncytiotrophoblast, in nuclei of syncytiotrophoblast and trophoblast cells as well in extravillous trophoblast cells of normal placentas. In GDM placentas, gal-13 expression was significantly decreased in all of these examined cell types (syncytiotrophoblast p = 0.003, nuclei of syncytiotrophoblast p = 0.007; extravillous trophoblast cells p = 0.001). The ELISA showed a significant lower gal-13 serum level in blood from pregnant women with GDM in comparison to healthy controls. DISCUSSION: As gal-13 with its anti-inflammatory functions plays a role in regulation of maternal immune system, a lack of gal-13 may contribute to an imbalance in inflammation processes in the placenta during pregnancy and therefore influences development of GDM.