Trophoblastic Components Research Articles

Malignant tumours of the uterus and ovaries with Mullerian and germ cell or trophoblastic components have a somatic origin and are characterised by genomic instability.

Tumours of the female genital tract with a combination of malignant Mullerian and germ cell or trophoblastic tumour (MMGC/T) components are usually diagnosed in postmenopausal women, and pursue an aggressive clinical course characterised by poor response to therapy and early relapses. These clinical features suggest that MMGC/T are somatic in origin, but objective molecular data to support this interpretation are lacking. This study evaluates the molecular features of nine MMGC/T, including seven tumours containing yolk sac tumour (YST), one tumour containing choriocarcinoma and one tumour containing epithelioid trophoblastic tumour. The objectives were to: (i) investigate whether MMGC/T show a distinct genetic profile and (ii) explore the relationship between the different histological components. Next-generation sequencing of paired samples demonstrated that the mutational profile of the Mullerian and non-Mullerian components of the tumour were almost identical in all cases. Moreover, the driver mutations identified were those expected in the specific subtype of Mullerian component present in each case. In contrast, variants expected in postpubertal germ cell tumours and gestational trophoblastic tumours were not identified, and FISH for i(12p) was negative in all cases tested. In this study, mismatch repair-proficient MMGC/T (eight of nine) were characterised by a complex copy-number variant profile, including numerous focal, regional, arm-level and chromosome-level events. Comparison of paired samples supports that the YST and trophoblastic tumour components of MMGC/T have a somatic origin and often show numerous copy-number variants, suggestive of underlying genomic instability.

Urothelial Carcinomas With Trophoblastic Differentiation, Including Choriocarcinoma: Clinicopathologic Series of 16 Cases.

Trophoblastic differentiation (including choriocarcinoma) arising in urothelial carcinoma has been described in numerous case reports, but never in a single series. We present a series of these tumors, describing the morphologic spectrum, applying traditional and novel immunohistochemical stains, and characterizing clinical follow-up. We identified 16 cases, arising predominantly in the bladder (N=14), but also the ureter (N=1) and prostatic urethra (N=1). Six of our cases (38%) contained invasive urothelial carcinoma with admixed syncytiotrophoblasts, 8 cases (50%) consisted of invasive urothelial carcinoma with choriocarcinoma, 1 case (6%) showed urothelial carcinoma in situ with associated choriocarcinoma, and 1 case (6%) consisted of pure choriocarcinoma. Other subtypes of variant morphology were seen in 5 of our cases (31%) and included squamous, glandular, lipoid, chordoid/myxoid, and sarcomatoid features. Given the limited specificity of human chorionic gonadotropin immunohistochemistry, we also studied the expression of a novel specific trophoblastic marker, hydroxyl-δ-5-steroid dehydrogenase, as well as Sal-like protein 4. Human chorionic gonadotropin expression was seen in nearly all cases (93%) but was often not limited to the trophoblastic component, staining the urothelial component also in 85% of the cases. Expression of hydroxyl-δ-5-steroid dehydrogenase was more sensitive and more specific, staining 100% of the cases and limited to trophoblasts in all but 1 case. Sal-like protein 4 expression was variable, staining trophoblast in only 50% of cases and staining the urothelial carcinoma component in 43% of those positive cases. Most of our tumors presented at a high stage and were associated with poor clinical outcomes, with at least muscle-invasive disease (pT2) in 10 of the 14 bladder tumors (71%), periureteric fat invasion in the ureter tumor (pT3), distant metastases in 7 of 16 cases (44%) and death of disease in 3 of the 15 patients with follow-up (20%). Our study describes a series of urothelial carcinomas with trophoblastic differentiation, demonstrating the morphologic spectrum of this entity, its frequent association with other subtypes of variant morphology, its characteristic immunoprofile, and its aggressive clinical behavior.

THE STUDY OF SERUM LIPID PROFILE IN PREGNANCY INDUCED HYPERTENSION IN JMC, JHALAWAR.

Only one group was investigated for serum lipid profile in third trimester of pregnancy in which included all PIH patients admitted in labor room in Department of Obstetrics in Jhalawar Medical College and was substantially compared with the normal values of Lipids in women. In this study we investigate the role of lipid profile in PIH. LDL value increase, HDL value decrease, TG value increase and VLDL value increase in PIH patients and also TG : HDL ration increased significantly in PIH patients. Dyslipidemia mediated activation of endothelial cells to placentally derived endothelial disturbing factors like lipid peroxides and trophoblastic components as possible contributors for pathogenesis of PIH. Thus assessment of blood lipids may be helpful in preventions of complications in PIH.
 Key Words: Bloodlipids, PIH, Dyslipidemia, Triglycerides, Low Density Lipoprotiens, High Density Lipoprotiens.

Endometrial Carcinoma With Trophoblastic Components: Clinicopathologic Analysis of a Rare Entity.

Somatic endometrial carcinomas with trophoblastic components have only rarely been described. To better characterize this distinctive combination of histotypes, we report herein 4 new cases, representing the largest cohort reported thus far, and review previously reported cases. The 4 new patients ranged in age from 61 to 77 yr (mean, 68 yr). The first patient had a grade 2 endometrioid carcinoma, surgical International Federation of Gynecology and Obstetrics stage IA, that recurred 5 months later at the vaginal apex with purely choriocarcinoma elements, suggestive of unsampled trophoblastic areas in the uterus. The 3 other patients were all International Federation of Gynecology and Obstetrics stage III, and included 2 cases of dedifferentiated endometrial carcinoma with 40% and 20% choriocarcinoma components, and 1 case of grade 1 endometrioid carcinoma with a 40% choriocarcinoma component. Postoperative serum β-human chorionic gonadotropin was elevated in all patients. All received adjuvant combination chemotherapy, but all were dead of disease with distant metastases at an average of 11.75 mo (range, 7-16 mo) after primary staging. Data from our cases were combined with those from 24 cases that had previously been reported in the literature between 1972 and 2016. Analysis of this combined data indicates that endometrial carcinoma with trophoblastic component is a rare neoplasm that occurs primarily in postmenopausal patients. The trophoblastic component is most commonly a choriocarcinoma and the somatic component is most commonly an endometrioid carcinoma or an adenocarcinoma/carcinoma reported without further specification; the somatic component may be a diverse array of histotypes or histotype admixtures. Serum and/or urine β-human chorionic gonadotropin is elevated in almost all patients, and fluctuations of β-human chorionic gonadotropin generally correlated with tumor relapses or recurrences. The stage distribution and patient outcomes in the current and previously reported patients suggests that trophoblastic differentiation usually, but not invariably denotes clinical aggressiveness.

Un cas de carcinome urothélial avec différenciation trophoblastique et revue de la littérature

We report the case of a 43-year-old woman, who was admitted for intense pelvic pains. Biological investigations showed an increase of β-HCG level. The abdomino-pelvic computed tomography revealed a voluminous mass infiltrating the bladder. A transurethral resection was performed. The histopathological examination evidenced an invasion of the bladder by a massive carcinomatous proliferation composed of clear epithelial cells with in some places syncytiotrophoblastic cells and rarely cytotrophoblastic cells. Immunohistochemical analyses revealed a staining of GATA-3 by the two components, an expression of p63 by the clear cell urothelial component and the immunoreactivity of β-HCG by the trophoblastic component. Ki-67 labeling index was very high. The diagnosis of mixt urothelial carcinoma with clear cells and trophoblastic differentiation was proposed. This is a rare difficult histopathological diagnosis which should be known by pathologists. It is correlated to a poor clinical outcome with a high tendency to lymph node or visceral metastases.

Comprehensive Immunohistochemical Study of Programmed Cell Death Ligand 1 (PD-L1): Analysis in 5536 Cases Revealed Consistent Expression in Trophoblastic Tumors.

Programmed cell death 1/programmed cell death ligand (PD-1/PD-Ls) axis is crucial for the modulation of immune responses and self-tolerance. Also, aberrant PD-L1 expression on the tumor cells or tumor-associated inflammatory cells accelerates immune evasion of tumor cells. In the past decade, PD-1/PD-L immune checkpoint inhibitors were introduced to cancer treatment trials and, in some cases, showed significant anticancer effects. PD-L1 immunohistochemical staining is considered a potential predictor of clinical response to PD-1/PD-L immune checkpoint inhibitor treatment. However, immunohistochemical data on PD-L1 expression in different types of cancer especially rare entities remain incomplete. In this study, PD-L1 expression was immunohistochemically analyzed in 5536 tumors including germ cell, epithelial, mesenchymal, melanocytic/neuroectodermal, and lymphohematopoietic tumors, as well as in a set of human normal tissues including a fetus. Immunohistochemical analysis was performed with E1L3N rabbit monoclonal antibody and Leica Bond Max automation using multitumor blocks containing up to 70 tumor samples. PD-L1 was constitutively and strongly expressed in placental trophoblasts as well as choriocarcinomas and trophoblastic components of germ cell tumors. Also, the neoplastic cells of classical Hodgkin lymphoma, anaplastic large cell lymphoma, schwannoma, thymoma, and squamous cell carcinoma of various sites frequently expressed PD-L1. In gastrointestinal adenocarcinomas, PD-L1-expression was associated with EBER positivity and mismatch-repair deficiency. In addition, PD-L1 was variably expressed in non-neoplastic macrophages and dendritic cells. PD-L1 immunohistochemistry may have some role in the immunophenotypic differential diagnosis of tumors and pinpointing potential candidates for anti-PD-1/PD-L immune checkpoint therapy.

Nonchoriocarcinomatous Trophoblastic Tumors of the Testis: The Widening Spectrum of Trophoblastic Neoplasia.

Tumors of trophoblastic derivation other than choriocarcinoma are very rare in the testis but have been reported on occasion in association with other germ cell tumors. Their morphologic spectrum is analogous to the trophoblastic tumors of the female genital tract including epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT). Herein we report our experience with 8 cases of trophoblastic tumors of testicular origin that lacked the features of choriocarcinoma; these included 4 ETTs, 1 PSTT, 1 unclassified trophoblastic tumor (UTT), 1 partially regressed choriocarcinoma with a monophasic morphology, and 1 hybrid tumor showing a mixture of adenocarcinoma and a UTT. All tumors occurred in young men 19 to 43 years old. Five arose de novo within the testis (2 ETTs, 1 UTT, 1 regressing choriocarcinoma, and the hybrid tumor) as a component of mixed germ cell tumors, and 3 (2 ETTs and 1 PSTT) were found in metastatic sites after chemotherapy. The trophoblastic component was minor (5% to 10%) in 6 tumors but was 95% of 1 metastatic tumor (ETT) and 50% of the hybrid tumor. Other germ cell tumor elements were identified in all cases, most commonly teratoma. The ETTs consisted of nodules and nests of squamoid trophoblast cells showing abundant eosinophilic cytoplasm, frequent apoptotic cells, extracellular fibrinoid material, and positivity for p63 and negativity for human placental lactogen (HPL). The PSTT showed sheets of discohesive, pleomorphic, mononucleated trophoblast cells that invaded blood vessels with fibrinoid change and were p63 negative and HPL positive. The UTT showed a spectrum of small and large trophoblast cells, some multinucleated but lacking distinct syncytiotrophoblasts, and was patchily positive for both p63 and HPL. The hybrid tumor had ETT-like and adenocarcinomatous areas that coexpressed inhibin and GATA3 but were negative for p63 and HPL, leading to classification of the trophoblastic component as UTT. Seven of the patients were alive and well on follow-up (8 to 96 mo; median, 39 mo), whereas the patient with the hybrid tumor died of liver metastases at 2 years. Our study verifies that trophoblastic neoplasms often having the features of nonchoriocarcinomatous gestational trophoblastic tumors may arise from the testis, occur either in the untreated primary tumor or in metastases after chemotherapy, and should be distinguished from choriocarcinoma given what appears to be a less aggressive clinical course.

Surgical Options for Pineal Region Tumors

Surgical Options for Pineal Region Tumors

Effect of the method of conception and embryo transfer procedure on mid-gestation placenta and fetal development in an IVF mouse model

Abnormal placentation is a potential mechanism to explain the increased incidence of low birthweight observed after IVF. This study evaluates, in a mouse model, whether the method of conception and embryo transfer affect placentation and fetal development. IVF blastocysts (CF1 x B6D2F1/J) were cultured in Whitten's medium (IVF(WM), n = 55) or K modified simplex optimized medium with amino acids (IVF(KAA), n = 56). Embryos were transferred to the uteri of pseudo-pregnant recipients. Two control groups were created: unmanipulated embryos produced by natural mating (in vivo group, n = 64) and embryos produced by natural mating that were flushed from uterus and immediately transferred to pseudo-pregnant recipients (flushed blastocysts, FB group, n = 57). At gestation age 12.5 days, implantation sites were collected and fixed; fetuses and placentas were weighed and their developmental stage (DS) evaluated. Placental areas and vascular volume fractions were calculated; parametric statistics were applied as appropriate. IVF fetuses showed a modest but significant delay in development compared with FB mice (P < 0.05). In addition, IVF conceptuses were consistently smaller than FB (P < 0.05). Importantly, these differences persisted when analyzing fetuses of similar DS. The placenta/fetus ratio was larger in the IVF group (IVF(WM) 0.95; IVF(KAA) = 0.90) than the FB group (0.72) (P < 0.05 for all comparisons). Gross morphology of the placenta and ratio labyrinth/fetal area were equivalent in the IVF and FB groups, as were percentage of fetal blood vessels, maternal blood spaces and trophoblastic components. In vitro embryo culture affects fetal and placental development; this could explain the lower birthweight in IVF offspring.

Chorangiocarcinoma: A Case Report and Review of the Literature

Chorangiocarcinoma is the name designated to a chorangioma with trophoblastic proliferation manifesting increased proliferative activity. Only 3 such cases have been published so far. Other studies challenged this entity by demonstrating that proliferation of the trophoblast around chorangioma is a common phenomenon. We present a case of a unique vascular lesion in a term placenta with a malignant trophoblastic component. Microscopic examination of a well-demarcated placental mass revealed a chorangioma with multiple nodules composed of pleomorphic cells displaying focal multinucleation, large areas of necrosis, and high mitotic activity. Immunohistochemical stains of these cells were strongly positive for pancytokeratin and the beta subunit of human chorionic gonadotropin and focally positive for HSD3B1. There was no invasion of the basement membrane, and no free-floating tumor cells in the intervillous space. No evidence of metastasis was found on follow-up of the mother and newborn. It is concluded that the tumor presented herein, displaying a histologically unequivocal malignant trophoblastic component in a benign chorangioma, is a true chorangiocarcinoma, and should be included within the category of gestational neoplasia as a tumor closely related to choriocarcinoma.

Brain metastasis from non-seminomatous germ cell tumors of the testis

Brain metastases from non-seminomatous germ cell tumors (NSGCTs) are rare and mainly occur in young men whose clinical condition is unimpaired. The records of 15 patients with brain metastasis from non-seminomatous germ cell tumors of the testis, who had been surgically treated between 1984 and 1998, were retrospectively reviewed. All of the patients had undergone surgery plus whole-brain radiotherapy (WBRT), and chemotherapy based on cisplatin. On admission they had a median age of 33 years and their mean Karnofsky performance scale (KPS) score was >70. Mean survival was 37.7 months. Eight patients had a survival period longer than 5 years. Five patients belonged to radiation therapy oncology group (RTOG) class I; all of them survived. There was a significant difference in survival time between patients in whom the brain metastasis was present at diagnosis (six survivors at 5 years; mean survival 53 months) and patients in whom the brain metastasis occurred during or after chemotherapy (two survivors at 5 years; mean survival 24 months) (P = 0.04). The presence of a trophoblastic component at histopathological analysis of the metastasis negatively influenced survival at univariate analysis. Multiple brain metastasis proved to be a significant risk factor at both univariate and multivariate analysis, while a metastatic residue with a diameter less than 2 cm after surgery did not negatively affect survival in our series. Prognosis is worst in patients with multiple brain metastases, in whom brain involvement occurred during or after cisplatin-based chemotherapy. Considering that these metastases are often both radiosensitive and chemosensitive, and mainly affect young men that are in very good clinical condition, we advocate aggressive treatment with surgery plus adjuvant radiotherapy and chemotherapy. This is mandatory in patients with large metastases (diameter >3 cm).

Confocal laser scanning microscope study of cytokeratin immunofluorescence differences between villous and extravillous trophoblast: cytokeratin downregulation in pre-eclampsia.

Pre-eclampsia is a disease characterized by failures in interstitial implantation. One product of the implantation process is the basal plate; a structure whose complexity makes it hard to fully appreciate the pathological changes in significant diseases of pregnancy. This article describes our use of CLSM immunofluorescence to examine the cytokeratin composition of the cells of trophoblastic origin in the term placental basal plate. Large differences in the content of the structural polymeric protein were compared using analysis of digital images. We show that greater pancytokeratin immunofluorescence is observed in extravillous cytotrophoblast cells as compared with villous trophoblast. There is a >30-fold difference in the mean area percent of the most intensely immunofluorescent pixels in the tissue containing these cells. This is a very high, statistically significant difference as defined by the Wilcoxon Signed Ranks Test Asym. Sig. (two-tailed): P < 0.001. The most invasive population of cells of the trophoblast lineage (the extravillous trophoblast) exhibits a significant reduction in cytokeratin immunofluorescence when comparisons of healthy and pre-eclamptic pregnancies are made. This ratio was 2.4:1. It was tested using the Mann-Whitney U-test. From healthy to pre-eclamptic the reduction was from mean rank 83.42((healthy)) to 51.13((pre-eclamptic)). The difference was very highly statistically significant (n = 53 + 75 = 128; U = 984.500; Z = -4.852; P < 0.001). There was also less cytokeratin-related immunofluorescence in villous trophoblast when healthy villi were compared with pre-eclamptic villi. The observed alterations in trophoblastic cytoskeletal components are expected to damage the anchorage and motility of cells. The extravillous trophoblast is known to be necessary for implantation. This leads to a cellular hypothesis of the failure of implantation resulting in reduced depth of uterine invasion and failure to adapt the spiral arterioles for low-pressure perfusion of the intervillus space, two well-known features of pre-eclampsia. The reduction in cytokeratin-related immunofluorescence in the villus trophoblast seen on comparing healthy term placentae with those from pre-eclamptics implies that the trophoblast is a weaker epithelial layer in the hypertensive pregnancy. This could account for the rise in deported trophoblast associated with pre-eclampsia. Deported trophoblast has been invoked as the systemic messenger that leads to generalized maternal hypertension seen in this condition.

Structure of the Definitive Placenta of the Tenrec, Echinops telfairi

Until recently, tenrecs were classified with insectivores in the order Lipotyphla, but nucleotide sequence data suggest they have closer affinities with a group of African mammals called Afrotheria. The placenta of Echinops has not been described and no studies involving electron microscopy of the placenta of any species of tenrec have been published. We used light and transmission electron microscopy to examine fixed placentae of embryos ranging from 25–66 mm in length. The placental disk is situated in the antimesometrial portion of the bicornuate uterus. The greater part of the disk consists of a labyrinth underlain by a spongy zone. The interhaemal barrier is unusual in that the trophoblastic component is a single layer of cytotrophoblast. These trophoblast cells have thick areas especially near the nuclei and extensive thin flanges but only occasionally have membrane-closed pore regions. The luminal surface has isolated patches of microvilli, and pinocytotic vesicles are numerous both apically and basally. In the centre of the placental disk is an elaborately folded haemophagous region. The primary folds have allantoic endoderm at one surface and columnar cytotrophoblast at the other. These trophoblast cells have numerous lipid droplets and vesicles, and often contain large yellow pigment crystalloids. The labyrinthine zone ends abruptly at the margins of the placental disk. However, the endoderm and connective tissue of the allantois and a layer of cytotrophoblast extend beyond the placental disk as a paraplacental region. Some of these distinctive features of Echinops placenta are shared with individual afrotherians, but no significant characteristic of definitive placentation is shared by all the Afrotheria.

Plasma lipids and vascular dysfunction in preeclampsia.

The dominating hypothesis of the preeclampsia syndrome (PES) is that placentally derived factors are released to the maternal circulation. These factors are believed to alter endothelial properties resulting in disturbed vasomotor function, increased endothelial permeability, and activation of thrombogenic factors. However, the impact of placentally derived factors on the endothelial cells is influenced by another major variable: the "sensitivity" of the maternal endothelium to the placental factors. Several maternal factors may play a role in determining this sensitivity. They include chronic hypertension, diabetes, and hyperlipidemia. In this article we discuss the possible role of hyperlipidemia (especially high free fatty acids and hypertriglyceridemia) in the pathogenesis of preeclampsia, viewed from this perspective. Pregnancy in general, preeclamptic pregnancy in particular, is associated with a marked hyperlipidemia. We suggest a parallel to atherosclerotic diseases, wherein hyperlipidemia induces endothelial dysfunction, probably by promoting oxidative stress in the arterial wall. The hyperlipidemia of pregnancy may have a similar effect on the endothelial cells. When placentally derived endothelial disturbing factors, like lipid peroxides and trophoblastic components, are released into the maternal circulation, their effects on the endothelium may be enhanced because of hyperlipidemia-mediated activation or "sensitization" of the endothelial cells. Alternatively, placentally derived factors like peroxides may combine with lipoproteins, forming complexes that are more disturbing to cells than the placental factors or lipoproteins are individually. We also discuss the possible role of maternal hyperlipidemia in aggravating placental insufficiency caused by poorly transformed spiral arteries. The hemodynamic flow pattern may be markedly different in completely and incompletely transformed spiral arteries. By analogy to the fundamental role of hemodynamic factors in development of atherosclerosis, we pose the hypothesis that abnormally transformed spiral arteries have an "atherogenic" blood flow pattern that promotes lipid deposition and "acute atherosis".

Diffuse Embryoma of the Testis:An Immunohistochemical Study of Two Cases

The authors report the histologic and immunohistochemical findings of two cases of diffuse embryoma of the testis, a distinct form of mixed-germ-cell tumor characterized by diffuse, orderly arrangement of embryonal carcinoma (EC) and yolk sac tumor (YST) with scattered trophoblastic components. The patients were 37 and 38 years old when they presented with a right testicular tumor, which was confined to the testis (stage I) in both cases. Histologically, the tumor was composed predominantly of intimately intermingled EC and YST components in almost equal proportion. The tumor cells were arranged in necklacelike fashion; the EC cells formed glandular structures rimmed by a single cell layer of YST cells. The YST component was highlighted by positive staining for alpha-fetoprotein and strong staining for cytokeratin, whereas the EC component was positive for Ki-1 (BerH2, CD30) antigen, was negative for alpha-fetoprotein, and stained more weakly for cytokeratin. The randomly distributed few trophoblastic elements stained for human chorionic gonadotropin. The patients are alive with no evidence of disease, 11 years and 9 months after surgery, respectively. This newly described but distinct variant of mixed-germ-cell tumor should be differentiated from polyembryoma, which is composed of multiple discrete embryoid bodies.

Epithelial localization of insulin-like growth factor binding protein 1 in the uterus of the rat during pregnancy, deciduoma-bearing pseudopregnancy and hormone treatment.

A monospecific antibody was used to determine the immunocytochemical localization of insulin-like growth factor binding protein 1 (IGFBP-1) in the rat uterus. Immunoreactive IGFBP-1 was first detected from day 5 of pregnancy in the luminal and glandular epithelium. However, immunoreactivity was most intense from day 6 in the glandular epithelium, where it was associated with apically located granules. Immunoreactive glands were located only in non-decidualized endometrium, which was limited at the implant site to a thin basal layer by growth of the antimesometrial decidua from day 7. However, glands and associated immunoreactive IGFBP-1 were prominent in the inter-implant sites until day 9, although they were detected throughout pregnancy. Similar reactivity was detected in the glands of the basal endometrium in deciduomata-bearing animals, but these decreased in number from day 7 of pseudopregnancy. No immunoreactivity was detected during the oestrous cycle but could be induced in ovariectomized animals by sequential oestradiol and oestradiol plus progesterone treatment. The observations were consistent with IGFBP-1 representing a secretory product of the glandular epithelium and could either play a role in development of the trophoblastic component of the conceptus during the pre-placental period of anti-mesometrial implantation or in the endometrium acting as an inhibitor of local IGF-I action and in either case by transporting IGF-I from the stromal to the glandular luminal environment.

Placental Site Trophoblastic Tumors (Trophoblastic Pseudotumors)

Placental site trophoblastic tumor (PSTT), which can be regarded as a subtype of gestational trophoblastic neoplasia is discussed. The histopathological features include trophoblastic proliferation without the typical organization of the bilamelar cyto and syncytiotrophoblastic villus. Ultrastructural investigation has demonstrated a clone structural relationship between the infiltrating cells and those of the trophoblastic components of the normal human placenta. Clinical management should be based on the complete surgical resection of the mass and a follow-up by measuring the serum levels of beta-human chorionic gonadotropin fractions.

Cytoskeleton of human embryonal carcinoma cells

Monoclonal antibodies to cytoskeletal proteins were used to study the intermediate filament proteins of human embryonal carcinoma (EC) cell lines, tumors produced in nude mice from these cell lines, and surgically removed testicular germ cell tumors. It was found that all cells of tumor lines 2102Ep, 1156 and Tera 1 react with antibodies to low molecular weight keratin proteins. By immunoblotting of SDS gels it was found that these lines expressed three keratin polypeptides (40K, 45K and 52K). Clonal line NTera-2 derived from Tera-2 differed from the above listed cell lines in that only 10% of the cells expressed the 40K keratin polypeptide. Upon treatment with retinoic acid 70% of NTera-2 cells became reactive with the antibody to the 40K keratin polypeptide. All cell lines contained a small population of vimentin-positive cells. The number of vimentin-positive cells could be increased by retinoic acid treatment of NTera-2 cells or by seeding the 2102Ep cells at low cell density. Neurofilament-positive cells could be induced in the cell line NTera-2 by retinoic acid treatment. Tumors produced from NTera-2 cells injected into nude mice contained cells reacting with antibodies to keratin, vimentin, neurofilament proteins and desmin. Keratin polypeptides were immuno-histochemically demonstrated in embryonal carcinoma, yolk sac carcinoma and trophoblastic components of solid human germ cell tumors. A typical intratubular cells (‘carcinoma in situ’) also reacted with antibodies to keratin.

In vitro susceptibility of mouse placental trophoblast to cytotoxic effector cells

The susceptibility of mouse placental cells to hyperimmune cell killing directed against paternal combined H-2 and non-H-2 antigens was investigated using [ 3H]uridine as a terminal label in an in vitro cell-mediated microcytotoxicity test. The stage of development of the conceptus from which the short-term placental cell monolayers were prepared determined their susceptibility to immune cell lysis. Cultures from whole placentae taken at 9 days post-coitum (p.c.) were not significantly affected whereas similar monolayers prepared at 10.5 days p.c. or later underwent extensive destruction. Embryonic fibroblasts were susceptible at all stages examined from 9–16 days p.c. The onset of susceptibility correlates with the reported appearance of H-2 antigens on the placenta during ontogeny. All cultures of dissected populations of 13-day p.c. placental spongiotrophoblast were susceptible but only 70% of those of labyrinthine trophoblast. It is suggested that of the two major trophoblastic components of the mouse placenta the spongiotrophoblast expresses antigens that render it vulnerable to maternal immune attack whilst the labyrinthine trophoblast is only weakly or non-antigenic, with the observed killing being due largely to contamination of these cultures by antigenic foetal mesenchymal elements. Since failure to express appropriate target antigens cannot be the reason for the in vivo survival of the spongiotrophoblast it must be presumed that some form of immunoregulatory mechanism(s) is responsible for the maintenance of the foeto-placental allograft.

Trophoblastic pseudotumor of the uterus:Case report and ultrastructure

A trophoblastic pseudotumor occurring in a young woman 6 months after a normal pregnancy is reported. Ultrastructural investigation demonstrated a close structural relationship between the infiltrating cells and those of the trophoblastic components of the normal human placenta, especially those seen in the primary villi of the developing placenta.