Invasive and metastatic hydatidiform moles in Slovakia in 1993‒2022.

OBJECTIVE: A retrospective analysis of invasive and metastatic hydatidiform moles (HM) in the Slovak Republic (SR)‒epidemiology, patient characteristics and treatment outcomes. BACKROUND: Invasive and metastatic mole is a highly curable type of gestational trophoblastic neoplasia. Both invasive and metastatic HM may be cured by hysterectomy without adjuvant chemotherapy. METHODS: Nineteen cases of histopathologically confirmed HM (10 invasive and 9 metastatic) were treated in SR from 1993 to 2022. Patients were divided into two groups according to treatment modality (hysterectomy only ‒ 8; hysterectomy and chemotherapy ‒ 11). The parameters included in the analysis were patient age, antecedent pregnancy, human chorionic gonadotropin level, tumor size and time to remission. RESULTS: The incidence of invasive and metastatic HM in the SR was 1:121,253 pregnancies, or 1:86,589 live births. The overall cure rate was 100%, without recurrence. Hysterectomy was performed as first-line therapy in 14 patients, with a cure rate of 57.1%. 4 out of 8 patients (50%) with metastatic moles, who underwent first-line hysterectomy, were cured without chemotherapy. There was no statistically significant difference between the two groups in all selected parameters. CONCLUSION: First-line hysterectomy may lead to remission without adjuvant chemotherapy or reduce the number of chemotherapies in invasive and metastatic HM (Tab. 4, Fig. 2, Ref. 21).

Combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios for early prediction of postmolar gestational trophoblastic neoplasia.

PURPOSE: To investigate factors predicting postmolar gestational trophoblastic neoplasia (GTN) by combined analysis of clinical features, human chorionic gonadotropin (hCG) value, and hCG ratios. METHODS: This retrospective study enrolled patients with histopathologically proven molar pregnancy. Patients lost to follow-up before remission or developing postmolar GTN were excluded. Demographic and clinical characteristics and hCG data obtained before and after molar evacuation were collected. Area under the receiver operating characteristic curve (AUC) analysis was used to identify the hCG and hCG ratio cutoff values that predict postmolar GTN. Multivariate analysis was employed to identify independent predictors of GTN. RESULTS: There were 113 complete moles, 11 partial moles, and 52 unspecified moles included in the final analysis. Of the 176 cases, 90 achieved remission and 86 developed post-molar GTN. The incidence of postmolar GTN was 48.9%, with a median time to GTN development of 5 weeks. Univariate analysis showed age, molar evacuation performed elsewhere, pre-evacuation hCG, hCG at 2nd week post-evacuation, and ratio of hCG at 2nd week post-evacuation to post-evacuation hCG significantly predict GTN. Multivariate analysis revealed an hCG value ≥ 1400 IU/L at 2nd week post-evacuation (AUC: 0.92, aOR: 6.51, 95% CI 1.28-33.16; p = 0.024) and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 (AUC: 0.88, aOR: 12.27, 95% CI 2.15-70.13; p = 0.005) to independently predict GTN. CONCLUSIONS: An hCG value ≥ 1400 IU/L at 2nd week post-evacuation and a ratio of hCG at 2nd week post-evacuation to post-evacuation hCG of ≥ 0.02 independently and reliably predict postmolar GTN.

An invasive mole with pulmonary metastases in a 55-year-old postmenopausal Syrian woman: a case report and review of the literature.

BACKGROUND: Invasive mole is a subtype of gestational trophoblastic neoplasms (GTNs) that usually develops from the malignant transformation of trophoblastic tissue after molar evacuation. Invasive moles mostly occur in women of reproductive age, while they are extremely rare in postmenopausal women. CASE PRESENTATION: We present the case of a 55-year-old postmenopausal Syrian woman who was admitted to the emergency department at our hospital due to massive vaginal bleeding for 10 days accompanied by constant abdominal pain with diarrhea and vomiting. Following clinical, laboratory and radiological examination, total hysterectomy with bilateral salpingo-oophorectomy was performed. Histologic examination of the resected specimens revealed the diagnosis of an invasive mole with pulmonary metastases that were diagnosed by chest computed tomography (CT). Following surgical resection, the patient was scheduled for combination chemotherapy. However, 2 weeks later the patient was readmitted to the emergency department due to severe hemoptysis and dyspnea, and later that day the patient died in spite of resuscitation efforts. CONCLUSION: Although invasive moles in postmenopausal women have been reported previously, we believe our case is the first reported from Syria. Our case highlights the difficulties in diagnosing invasive moles in the absence of significant history of gestational trophoblastic diseases. The present study further reviews the diagnostic methods, histological characteristics and treatment recommendations.

Heterozygous/dispermic complete mole confers a significantly higher risk for post-molar gestational trophoblastic disease.

Hydatidiform moles are classified at the genetic level as androgenetic complete mole and diandric-monogynic partial mole. Conflicting data exist whether heterozygous complete moles are more aggressive clinically than homozygous complete moles. We investigated clinical outcome in a large cohort of hydatidiform moles in Chinese patients with an emphasis on genotypical correlation with post-molar gestational trophoblastic disease. Consecutive products of conceptions undergoing DNA genotyping and p57 immunohistochemistry to rule out molar gestations were included from a 5-year period at Beijing Obstetrics and Gynecology Hospital. Patient demographics and clinical follow-up information were obtained. Post-molar gestational trophoblastic disease or gestational trophoblastic neoplasia was determined by the 2002 WHO/FIGO criteria. A total of 1245 products of conceptions were classified based on genotyping results into 219 complete moles, 250 partial moles, and 776 non-molar gestations. Among 219 complete moles, 186 were homozygous/monospermic and 33 were heterozygous/dispermic. Among 250 partial moles, 246 were triploid dispermic, 2 were triploid monospermic, and 2 were tetraploid heterozygous partial moles. Among 776 non-molar gestations, 644 were diploid without chromosomal aneuploidies detectable by STR genotyping and 132 had various genetic abnormalities including 122 cases of various trisomies, 2 triploid digynic-monoandric non-molar gestations, 7 cases of possible chromosomal monosomy or uniparental disomy. Successful follow-up was achieved in 165 complete moles: post-molar gestational trophoblastic disease developed in 11.6% (16/138 cases) of homozygous complete moles and 37.0% (10/27 cases) of heterozygous complete moles. The difference between the two groups was highly significant (p = 0.0009, chi-square). None of the 218 partial moles and 367 non-molar gestations developed post-molar gestational trophoblastic disease. In conclusion, heterozygous/dispermic complete moles are clinically more aggressive with a significantly higher risk for development of post-molar gestational trophoblastic disease compared with homozygous/monospermic complete moles. Therefore, precise genotyping classification of complete moles is important for clinical prognosis and patient management.

A case report of pelviscopic resection of invasive hydatidiform mole.

RATIONALE: Invasive moles occur in the fertile period, with about 95% occurring after previous mole removal and the remaining 5% occurring after several other pregnancies. PATIENT CONCERNS: A 27-year-old patient developed a rare invasive mole two months after a missed abortion. DIAGNOSES: A transvaginal ultrasound scan revealed a 3.6 × 2.9 × 2.4 cm sized lesion with cystic vascular areas within it, within the myometrium of the right fundal posterior region of the uterus. There was no metastasis to other organs. INTERVENTIONS: After administration of methotrexate, the level of beta-human chorionic gonadotropin (ß-hCG) was elevated and liver enzymes were also markedly elevated. She wanted to retain fertility for future pregnancies. After laparoscopic removal of the myometrial invasive mole, the incision site was sutured with a 3-0 V-Loc. OUTCOMES: One year later, a natural pregnancy occurred and a cesarean section was performed at 36 weeks. LESSONS: This is the first reported case of its type. Our case demonstrated that pelviscopic removal of an invasive mole is possible if there are no other metastases, and that future pregnancy and childbirth are still feasible in women of reproductive age.

Proteomic identification of predictive biomarkers for malignant transformation in complete hydatidiform moles.

INTRODUCTION: Protein expression in cells are associated with oncogenesis. This study aims to explore proteomic profiles and discover potential biomarkers that can predict malignant transformation of hydatidiform mole. METHODS: Retrospective analysis was done in 14 cases of remission hydatidiform mole and 14 cases of hydatidiform mole who later developed malignancy (GTN group). Molar tissues were retrieved from -70 °C frozen tissue. Subsequently, a large-scale proteomic analysis was performed to identify proteins and compare their abundance levels in the preserved molar tissues from these two groups using a dimethyl-labeling technique coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 2,153 proteins were identified from all samples. 22 and 10 proteins were significantly up-regulated and down-regulated, respectively, in the GTN group compared with the mole group. These altered proteins were found in several biological groups such as cell-cell adhesion, secreted proteins, and ribonucleoproteins. Several hormone-related proteins were among the most up-regulated proteins in the GTN group including choriogonadotropin subunit beta (ß-hCG) and alpha (α-hCG), growth/differentiation factor 15, as well as both pregnancy-specific beta-1-glycoproteins 2 and 3. In contrast, protein S100-A11 and l-lactate dehydrogenase A chain, were down-regulated in molar tissue from most patients in the GTN group. DISCUSSION: This study identified a set of differentially expressed proteins in molar tissues that could potentially be further examined as predictive biomarkers for the malignant transformation of CHMs. A molar proteome database was constructed and can be accessible online at http://sysbio.chula.ac.th/Database/GTD_DB/Supplementary_Data.xlsx.

Histopathological and clinical features of molar pregnancy.

OBJECTIVE: To analyse own set of molar pregnancies and to develop clinically relevant procedures. TYPE OF STUDY: Review article with analysis of own data. SETTINGS: Department of Pathology 3rd Faculty of Medicine, Charles University, Faculty Hospital Královské Vinohrady, Prague; Department of Obstetrics and Gynecology 3rd Faculty of Medicine, Charles University, Faculty Hospital Královské Vinohrady, Prague. INTRODUCTION: The study monitors the decrease of laboratory values of beta-subunit of hCG gonadotropin (beta-hCG) after evacuation of partial and complete hydatidiform moles in a set of 45 partial and 46 complete moles. Two case reports of invasive moles. RESULTS: In cases of partial hydatidiform moles there was complete regression of beta-hCG in all cases, 89% regressed in six weeks, none of the women showed no subsequent elevation after reaching negativity. In cases of complete hydatidiform moles the decrease was less gradual, the negativity after six weeks was confirmed in 78%, three complete moles became malignant. CONCLUSION: The decrease of beta-hCG after molar pregnancy termination is variable. Even if in cases of complete hydatidiform moles the risk of malignization after reaching negativity is low, beta-hCG checks are recommended at monthly intervals for 6 months. Correct diagnosis of complete mole and its differentiation from partial mole can be achieved using immunohistochemistry - p57 antibody.

Sudden death due to an invasive mole in a young primigravida: Precipitous presentation masquerading the natural manner.

Pulmonary metastasis is a well-known complication of an invasive mole. However, sudden death due to haemoptysis resulting from a metastatic invasive mole is extremely rare. We report the sudden unexpected death of an 18-year-old primigravida following a molar pregnancy. The death event was complicated within a few days of presentation by a clinically unsuspected mole invading the lung vasculature with associated widespread metastatic calcifications in the liver and brain. Death was due to haemorrhagic shock as a result of massive haemoptysis resulting from the invasive mole metastasising to the pulmonary vasculature. This was substantiated with a post-mortem computed tomography and gross and histopathological findings at autopsy. This case highlights the need for a high index of suspicion about potentially life-threatening pulmonary metastasis in women with trophoblastic diseases.

Molar pregnancy with normal viable fetus presenting with severe pre-eclampsia: a case report.

BACKGROUND: While gestational trophoblastic disease is not rare, hydatidiform mole with a coexistent live fetus is a very rare condition occurring in 0.005 to 0.01% of all pregnancies. As a result of the rarity of this condition, diagnosis, management, and monitoring will remain challenging especially in places with limited resources and expertise. The case we report is an interesting rare case which presented with well-described complications; only a few similar cases have been described to date. CASE PRESENTATION: We report a case of a 21-year-old local Sarawakian woman with partial molar pregnancy who presented with severe pre-eclampsia in which the baby was morphologically normal, delivered prematurely, and there was a single large placenta showing molar changes. CONCLUSION: Even though the incidence of this condition is very rare, recognizing and diagnosing it is very important for patient care and it should be considered and looked for in patients presenting with pre-eclampsia.

[Effects of prophylactic chemotherapy on outcomes and prognosis of patients older than 40 years with invasive mole].

Objective: To discuss the effects of prophylactic chemotherapy on the outcomes and prognosis of invasive mole patients. Methods: One hundred and fifteen invasive mole (IM) patients older than 40 years were registered in Peking Union Medical Collage Hospital.Eleven of them were treated with prophylactic chemotherapy before diagnosed as IM prophylactic chemotherapy group, while the other 104 cases received therapeutic chemotherapy after diagnosed as IM (non-prophylactic chemotherapy group). The general clinical data (including age, clinical stage, risk factor score), treatment, outcomes and relapse of patients were retrospectively compared between two groups. Results: (1) The age of prophylactic chemotherapy group and non-prophylactic chemotherapy group were (47±5) versus (46±4) years old. Ratio of clinical stageⅠ-Ⅱ were 3/11 versus 29.8% (31/104), clinical stage Ⅲ-Ⅳ were 8/11 versus 70.2% (73/104). Ratio of risk factor score 0-6 were 11/11 versus 84.6% (88/104), risk factor score >6 were 0 versus 15.4% (16/104). There were no significant statistical differences between two groups in age, clinical stage or risk factor score (all P>0.05). (2) Treatment: the total chemotherapy courses between prophylactic chemotherapy group and non-prophylactic chemotherapy group (median 7 versus 5) were significantly different (Z=3.071,P=0.002). There were no significant statistical differences between two groups in the chemotherapy courses until negative conversion of ß-hCG, consolidation chemotherapy courses, total therapeutic chemotherapy courses or ratio of hysterectomy (all P>0.05). (3) Outcomes and relapse: between the prophylactic chemotherapy group and the non-prophylactic chemotherapy group, the complete remission rate were 11/11 versus 98.1%(102/104), the relapse rate were 0 versus 1.0%(1/102). There were no significant difference between the two groups in outcomes or relapse rate (P>0.05). Conclusions: Prophylactic chemotherapy does not substantially benefit the IM patients older than 40 years. Prophylactic chemotherapy may not significantly improve patients' prognosis, in which increased sample size is required in further study.

N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma.

Gestational trophoblastic neoplasia (GTN) results from the malignant transformation of placental trophoblasts which secrete human chorionic gonadotropin (hCG) as do normal placenta or hydatidiform mole. N-acetylglucosaminyltransferase IV (GnT-IV) is a glycosyltransferase which catalyses the formation of ß1,4GlcNAc branches on the mannose core of N-glycans. Previous studies reported that ß1,4GlcNAc branches on hCG were detected in GTN but not in normal pregnancy or hydatidiform mole. The aim of the present study was to understand the role of GnT-IVa in choriocarcinoma and find the target proteins for GnT-IVa glycosylation which contribute to the malignancy of choriocarcinoma. Immunohistochemistry showed that Griffonia simplicifolia lectin-II staining and GnT-IVa staining were intense in trophoblastic cells of invasive mole and choriocarcinoma. We established a choriocarcinoma cell line with GnT-IVa overexpression (Jar-GnT4a), and examined its malignant potential and target proteins for GnT-IVa glycosylation. GnT-IVa overexpression increased the cell migration and invasion (2.5- and 1.4-fold) as well as the ability to adhere to the extracellular matrix (ECM) components, including fibronectin and collagen type I and IV. The tumour formation potential of Jar-GnT4a in mice was significantly higher than that of control (P=0.0407), and the cumulative survival rate of mice with Jar-GnT4a was relatively lower than those with control. Immunoprecipitation studies showed that ß1,4GlcNAc branches of N-glycans on integrin ß1 in choriocarcinoma cells were increased by GnT-IVa overexpression. Nano-LC/MS/MS analysis suggested that lysosome-associated membrane glycoprotein 2 (LAMP-2) was a target protein for glycosylation by GnT-IVa. The increase in ß1,4GlcNAc branches on LAMP-2 by GnT-IVa overexpression was confirmed by lectin blot analysis using whole cell lysate and conditioned medium. Our results suggest that highly branched N-glycans generated by the action of GnT-IVa are present in trophoblastic cells of GTN in proportion to GnT-IVa expression level, and that GnT-IVa may contribute to the malignancy of choriocarcinoma by promoting cell adhesion, migration and invasion through glycosylation of integrin ß1 and LAMP-2.

[Clinical and radiological features of gestational trophoblastic tumors]. / Tumeurs trophoblastiques gestationnelles: aspects cliniques et radiologiques.

Gestational trophoblastic disease incorporates a group of diseases which differ from each other by their regressive evolution, their evolution to metastasis and to recurrence. It is a severe disease that affects women of childbearing age. Gestational trophoblastic tumors (GTT) are the malignant forms of gestational trophoblastic diseases. They are always a result of pregnancy, more often molar pregnancy (hydatidiform mole). The most common type of gestational trophoblastic tumors (GTT) is the invasive mole because, in most cases, the diagnosis is made when cancer is still confined to the uterus. Choriocarcinoma is a more rare type of tumor, often developing distant metastases. When there is a progression to a trophoblastic tumor, the assessment of locoregional extension and distant metastases is essential to establish an appropriate treatment protocol. We here report three clinical cases of GTT by describing their clinical presentations and the use of imaging techniques in the diagnosis and management of these disorders.

Laparoscopic Management of an Invasive Mole Perforating the Uterus.

STUDY OBJECTIVE: To show the possibility of conservative laparoscopic management in a case of invasive mole perforating the uterus. DESIGN: Video with explanations. SETTING: An invasive mole is a potentially life-threatening complication of gestational trophoblastic disease [1]. This is a case of a 24-year-old female presenting with abdominal pain and vaginal bleeding. There have been several previous reports of cases of uterine perforation by an invasive mole, all of which were managed with abdominal hysterectomy [2-7]. To our knowledge, this is the first report of an invasive mole perforation with active bleeding managed by laparoscopy without hysterectomy. INTERVENTIONS: Sonography revealed a large amount of fluid and a 3 × 3-cm heterogeneous lesion next to the posterior uterine wall. Her hemoglobin level dropped from 10.6 mg/dL to 8.6 mg/dL, and her ß-human chorionic gonadotropin level was 19,004 mIU/mL. On laparoscopy, ∼2500 mL of hemoperitoneum was found, along with an actively bleeding bulging mass in the posterior uterine wall. This mass was dissected, and hemostasis was secured with sutures and electrocoagulation. Pathology confirmed the diagnosis of a complete mole. After surgery, the patient was treated with 5 courses of a methotrexate-folinic acid regimen. Her recovery was uneventful. CONCLUSION: Uterine perforation by an invasive mole can be managed conservatively with laparoscopic surgery and postoperative chemotherapy. The transmural lesion will increase the risk of future uterine rupture during pregnancy in this patient.

Invasive mole in a perimenopausal woman: a case report and systematic review.

OBJECTIVE: Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumors. We present a case of a perimenopausal woman with invasive mole. A systematic review was performed to identify reports on GTD in older women and to determine adequate treatment options. CASE: A 51-year-old perimenopausal woman was admitted to hospital with abdominal feeling of pressure and nausea. Diagnostic curettage revealed hydatidiform mole. She also presented symptomatic hyperthyroidism with hypertensive blood pressure and uneasiness. After treatment with beta blockers and carbimazole, the patient underwent abdominal hysterectomy and bilateral oophorosalpingectomy. Histopathological examination confirmed an invasive hydatidiform mole (IHM). Serum ß-hCG has decreased from initially 300,000-100 unit/L after 4 weeks. DATA SOURCES: A systematic review was performed to identify all prior cases of GTD in women over 50. We searched in Medline, The Cochrane Library and Embase, to identify any articles published in the English language after 1970 and before Oct 31, 2013 pertaining to GTD in older woman (50 years or older). TABULATION, INTEGRATION, AND RESULTS: Ten records were included in the systematic review, involving 203 cases of trophoblastic disease in older women. Although the diagnosis of GTD in older women is rare, it should be considered especially in patients with suspicious intrauterine findings in transvaginal ultrasound examinations. Different treatments were performed. In a limited number of reports, older women with GTD underwent initial hysterectomy. Benefits are avoidance of chemotherapy-induced toxicity and reduced risk of recurrence. Hysterectomy should be performed by an experienced surgeon. CONCLUSION: It is concluded that GTD is very rare in peri- or postmenopausal women. Treatment has to be individualized, and hysterectomy can be considered as an appropriate option.

Differential expression patterns of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) -1, -4, -5, and -14 in human placenta and gestational trophoblastic diseases.

CONTEXT: The ability of intermediate trophoblasts to invade maternal tissue during placentation depends on how well they can degrade the extracellular matrix. Invasion into the extracellular matrix requires many complex proteases. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a novel family of secreted metalloproteinases. The ADAMTS-1, -4, -5, and -14 subtypes are known to be expressed in human placenta, but little is understood about their expression patterns. OBJECTIVE: To examine the expression patterns of ADAMTS-1, -4, -5, and -14 in specific human placenta cell types during gestation and in gestational trophoblastic diseases. DESIGN: Placental tissues were obtained from 25 pregnant women and 21 cases of gestational trophoblastic diseases (10 early complete moles, 3 placental site trophoblastic tumors, 4 invasive moles, and 4 choriocarcinomas). The expression of the 4 ADAMTS was analyzed by immunohistochemistry. RESULTS: ADAMTS-1, -4, -5, and -14 were differentially expressed by the human placenta throughout gestation in a time-specific and cell type-specific manner, as well as in gestational trophoblastic diseases. ADAMTS-1 showed gradually strong staining intensity in gestational trophoblastic diseases according to the invasive potential but showed consistent strong intensity throughout normal placenta. ADAMTS-4 and ADAMTS-5 exhibited higher and restricted expression in first-trimester intermediate trophoblasts. They also exhibited comparably strong expression in gestational trophoblastic diseases. However, ADAMTS-14 expression remained unchanged throughout gestation. CONCLUSIONS: The restricted expression pattern of ADAMTS-4 and ADAMTS-5 and their increased expression in gestational trophoblastic diseases suggest that these 2 ADAMTS subtypes are associated with a biological phenotype of trophoblasts involved in human placentation and the development of gestational trophoblastic diseases.

Rare Presentation of Chorioadenoma Destruens as Acute Haemoperitoneum Mimicking Ruptured Ectopic Pregnancy.

Gestational trophoblastic neoplasms (GTN) are proliferative degenerative disorders of placental elements and include complete or partial mole (90%), invasivemole (5-8%), choriocarcinoma (1-2%) and placental site tumor (1-2%). Chorioadenoma destruens is a trophoblastic tumor, characterized by myometrial invasion through direct extension or via venous channels. We present a case of invasive mole eroding uterus and uterine vasculature, causing sudden rupture of uterus with massive haemoperitoneum mimicking ectopic pregnancy. A 20 year old G1P0 at 6 weeks gestation presented in Casualty of Kasturba Hospital complaining of severe acute onset lower abdominal pain for one hour. Clinical examination revealed shock. Sonography suggested ectopic pregnancy and immediate exploratory laparotomy was decided. On laparotomy, 2000cc of haemoperitoneum was noted. Grape like vesicles protruding through fundal perforation with profuse active bleeding was seen. Bleeding persisted despite evacuation. Step wise uterine devascularisation failed to achieve haemostasis. Total abdominal hysterectomy was performed as a life saving measure.

Decorin and biglycan immunolocalization in non-villous structures of healthy and pathological human placentas.

AIMS: Decorin and biglycan are members of the small leucine-rich proteoglycan family, and constituents of both the extracellular matrix (ECM) and the cell surface. They are recognized as important factors in the control of proliferation, migration and invasion in vivo and in vitro. In this study, the localization patterns of decorin and biglycan were determined in healthy placentas and in highly invasive placental pathologies. METHODS AND RESULTS: The study included immunolocalization of decorin and biglycan in samples of first-trimester and term placentas, placenta accreta, invasive mole, and choriocarcinoma. Extravillous cytotrophoblast (EVT) cells were positive for both proteoglycans in all pathologies and in first-trimester placentas, although not in term placentas. Biglycan was immunolocalized in the ECM of all healthy and pathological placentas, whereas decorin was observed only in term placenta ECM. CONCLUSIONS: The expression of both proteoglycans was cell-specific and gestation time-dependent in healthy placentas, and was associated with invasive EVT cells in pathological placentas. In view of the biological properties of these molecules, it is possible that the biglycan pattern found here is intrinsically implicated in the invasive activity of EVT cells in both healthy and disordered placentas.