Publications of Frédéric GOFFIN
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See detailImproved computer-assisted analysis of the global lymphatic network in human cervical tissues.
BALSAT, Cédric ULiege; Signolle, N; Goffin, Frédéric ULiege et al

in Modern Pathology (2017), 30(2), 313

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See detailREGISTRE BELGE ET CENTRES DE RÉFÉRENCE POUR LES MALADIES TROPHOBLASTIQUES GESTATIONNELLES
DELCOMINETTE, Sarah ULiege; TIMMERMANS, Marie ULiege; DELBECQUE, Katty ULiege et al

in Revue Médicale de Liège (2015), 70(11), 550-556

Gestational trophoblastic diseases include placental pathologies comprising fertilization abnormalities (hydatidiform moles) and malignant lesions (choriocarcinoma, placental site trophoblastic tumor and ... [more ▼]

Gestational trophoblastic diseases include placental pathologies comprising fertilization abnormalities (hydatidiform moles) and malignant lesions (choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor). Due to their low incidence and heterogeneity, their diagnosis, management and treatment are not always optimal. Following the example of other European countries, a national registration system with two reference centers has been set up to guide physicians and patients and to propose individualized management. The centers offer their expertise through a systematic centralised pathology review by a panel of experts. HCG values are plotted in regression curves. In case of gestational trophoblastic neoplasia, an imaging work-up is proposed, from which the FIGO score and stage are derived and will guide the choice of treatment. Belgian centers offer a multidisciplinary approach, in partnership with the referent physician. More information for practitioners and patients is available on a web site: www.mole-chorio-bgog.eu, which also harbours a forum of discussion. [less ▲]

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See detailEvaluation of CellSolutions BestPrep(R) Automated Thin-Layer Liquid-Based Cytology Papanicolaou Slide Preparation and BestCyte(R) Cell Sorter Imaging System.
Delga, Agnes; GOFFIN, Frédéric ULiege; Kridelka, Frédéric ULiege et al

in Acta Cytologica (2014)

Objective: A double-blind study was conducted to compare the performance of the new BestPrep(R) (CellSolutions) liquid-based thin-layer Papanicolaou (Pap) test with ThinPrep(R) (Hologic). Study Design ... [more ▼]

Objective: A double-blind study was conducted to compare the performance of the new BestPrep(R) (CellSolutions) liquid-based thin-layer Papanicolaou (Pap) test with ThinPrep(R) (Hologic). Study Design: Samples from the study patients (n = 105) were collected twice in the same encounter with the ThinPrep sample always taken first and the BestPrep sample collected second. Slides were prepared according to both manufacturers' protocols and evaluated using manual microscopic review and the BestCyte(R) cell sorter imaging system (CellSolutions). Diagnostic truth for each case was determined by independent manual review of both slides by multiple pathologists and histology when available. The presence of atypical squamous cells of undetermined significance was the threshold for positive for sensitivity and specificity calculations. Results: BestPrep and ThinPrep, by manual review, had sensitivities for high-grade squamous intraepithelial lesion (HSIL) cases of 100 and 95.6%, respectively. Using the BestCyte cell sorter, both had 100% sensitivity. For the same HSIL cases, the digene HC2 high-risk human papillomavirus DNA test had sensitivities of 100% (BestPrep) and 95.6% (ThinPrep). Specificities were 71.4% (BestPrep) and 54.8% (ThinPrep). Conclusions: BestPrep was equivalent to ThinPrep for manual review even though BestPrep was always the second sample collected. The BestCyte cell sorter provides a practical alternative to manual review for both BestPrep and ThinPrep slides. (c) 2014 S. Karger AG, Basel. [less ▲]

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See detailElévation faible d’hCG en dehors d’un contexte gravidique : à propos de deux cas et revue de la littérature
DE BACKER, Benjamin ULiege; GOFFIN, Frédéric ULiege; NISOLLE, Michelle ULiege et al

in Annales de Biologie Clinique (2013), 71(4), 496-502

Unexpected finding or persistence of low human chorionic gonadotropin (hCG) levels is not a rare situation. It requires a clinico-biological approach in order to avoid misunderstandings that could lead to ... [more ▼]

Unexpected finding or persistence of low human chorionic gonadotropin (hCG) levels is not a rare situation. It requires a clinico-biological approach in order to avoid misunderstandings that could lead to inappropriate diagnostic or therapeutic attitudes. Beyond pregnancy, persistent low levels of hCG may be associated with various benign and malignant conditions, i.e. quiescent gestational trophoblastic disease (QTD), raised pituitary hCG or false positive elevation caused by circulating heterophile antibodies. We report the cases of two non-pregnant patients with low serum hCG. In the first case, hCG levels raised during several years following a spontaneous abortion. The likelihood of heterophilic antibodies interference was ruled out and extensive clinical investigation excluded the presence of a tumour. The diagnosis was QTD. In the second case, elevated hCG came to light as an incidental finding in a women with chronic renal failure and led the clinicians to question the laboratory. The cause was probably an increase in pituitary hCG consecutive to terminal renal failure. These cases illustrate the importance of understanding the biology of the hCG and the causes of its persistent low elevation, which are reviewed in this article. It is essential to demonstrate clinically the presence of a tumour in order to avoid unnecessary and ineffective chemotherapy and/or hysterectomy. [less ▲]

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See detailPlace de la radiotherapie dans le traitement des carcinomes epidermoides vulvaires. A propos d'un cas et revue de la litterature.
Werenne, X.; Hermesse, J.; Coucke, Philippe ULiege et al

in Revue Médicale de Liège (2013), 68(7-8), 391-5

Locally advanced squamous cell carcinoma of the vulva is treated with concomitant chemoradiotherapy if surgery is too mutilating and/or implies the use of stomy. We report in this paper, the unusual case ... [more ▼]

Locally advanced squamous cell carcinoma of the vulva is treated with concomitant chemoradiotherapy if surgery is too mutilating and/or implies the use of stomy. We report in this paper, the unusual case of a young patient treated successfully with this non-surgical approach. [less ▲]

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See detailAtypical recurrence of a placental site trophoblastic tumor four years after hysterectomy for benign condition: Case report and review of literature.
RAUW, Laetitia ULiege; DELBECQUE, Katty ULiege; GOFFIN, Frédéric ULiege et al

in Gynecologic Oncology Case Reports (2013), 6

*Rare case of PSTT limited to the vagina presenting eight years after last pregnancy and four years after hysterectomy*Differential diagnosis with other vaginal tumors can be challenging but it is ... [more ▼]

*Rare case of PSTT limited to the vagina presenting eight years after last pregnancy and four years after hysterectomy*Differential diagnosis with other vaginal tumors can be challenging but it is critical because behavior and management are different.*Stage-adapted management is proposed and surgery is the mainstay treatment for localized disease. [less ▲]

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See detailDifferential expression of Vegfr-2 and its soluble form in preeclampsia.
Munaut, Carine ULiege; LORQUET, Sophie ULiege; Pequeux, Christel ULiege et al

in PLoS ONE (2012), 7(3), 33475

Background: Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably ... [more ▼]

Background: Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta. METHODOLOGY/PRINCIPAL FINDINGS: By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction. [less ▲]

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See detailBelgian experience of robot assisted laparoscopic para – aortic lymphadenectomy for staging of locally advanced cervical carcinoma. A multicentric study.
Fastrez, M; GOFFIN, Frédéric ULiege; Vergote, I et al

Poster (2012)

Objectives: FIGO clinical staging, imaging techniques sometimes underestimate extension of locally advanced cervical cancer (LACC). The presence of para-aortic lymph node (LN) metastases in LACC ... [more ▼]

Objectives: FIGO clinical staging, imaging techniques sometimes underestimate extension of locally advanced cervical cancer (LACC). The presence of para-aortic lymph node (LN) metastases in LACC identifies patients with poor prognosis. Laparoscopic para-aortic lymphadenectomy is now proposed as a diagnostic tool. Feasibility and safety of robot assisted laparoscopic para-aortic lymphadenectomy has been reported. We collected data from different Belgian centers to assess its oncological safety and complication rate. Study design: Three centers participated in the study. Thirty seven patients with LACC underwent a pre treatment robot assisted laparoscopic para-aortic lymphadenectomy. Data was prospectively collected. Results: The median number of LN collected was 27.5 (1-54) per patient. Five out of 37 patients had para-aortic node metastasis. The false negative rate for PET CT diagnosing para- aortic node metastasis was 10.8% (4/37). We encountered 2 major intra operative complications (5.4%). Post operative morbidity was low (13.5%). Median follow up was 27 months (95% CI 24–30). Median disease free survival (DFS) was 16 months (95% CI 2.4- 29.6). Patients with negative LN had a median DFS of 24 months (NA) although patients with positive LN had a median DFS of 9 months (95% CI 6.9-11.9). Conclusions: In this series we report that robot assisted laparoscopic para-aortic lymphadencetomy provided the surgeon with useful information to avoid understaging in 10.8% of women with LACC, at the expense of low morbidity (13.5%). Presence of microscopic para-aortic LN metastasis is correlated with shorter DFS. The number of patients with positive LN doesn’t allow us to draw any firm conclusion. [less ▲]

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See detailWhole Slide Quantification of Stromal Lymphatic Vessel Distribution and Peritumoral Lymphatic Vessel Density in Early Invasive Cervical Cancer: A Method Description
Balsat, Cédric ULiege; Blacher, Silvia ULiege; Signolle, Nicolas et al

in ISRN Obstetrics and Gynecology (2011), 2011

Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional ... [more ▼]

Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional optical microscopy and the hot spot technique, interobserver variability is significant and yields inconsistent conclusions. In this work, we describe an original method that applies computed image analysis to whole slide scanned tissue sections following immunohistochemical lymphatic vessel staining. This procedure allows to determine an objective LVD quantification as well as the lymphatic vessel distribution and its heterogeneity within the stroma surrounding the invasive tumor bundles. The proposed technique can be useful to better characterize lymphatic vessel interactions with tumor cells and could potentially impact on prognosis and therapeutic decisions. [less ▲]

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See detailAnalysis of 13 Million Individual Patient Records Pertaining To Pap Smears, Colposcopies, Biopsies and Surgery on The Uterine Cervix (Belgium, 1996–2000)
Arbyn, Marc; Simoens, C.; Van Oyen, H. et al

in Preventive Medicine (2009)

Objective Cervical cancer screening by surveys overestimate coverage because of selection and reporting biases. Methods The prepared Inter-Mutualistic Agency dataset has about 13 million records from Pap ... [more ▼]

Objective Cervical cancer screening by surveys overestimate coverage because of selection and reporting biases. Methods The prepared Inter-Mutualistic Agency dataset has about 13 million records from Pap smears, colposcopies, cervical biopsies and surgery, performed in Belgium between 1996 and 2000. Cervical cancer screening coverage was defined as the proportion of the target population (women of 25–64 years) that has had a Pap smear taken within the last 3 years. Proportions and incidence rates were computed using official population data of the corresponding age group, area and calendar year. Results Cervical cancer screening coverage, in the period 1998–2000, was 59% at national level, for the target age group 25–64 years. Differences were small between the 3 regions. Variation ranged from 39% to 71%. Coverage was 64% for 25–29 year old women, 67% for those aged 30–39 years, 56% for those aged 50–54. The modal screening interval was 1 year. In the 3-year period 1998–2000, 3 million smears were taken from the 2.7 million women in the age group 25–64. Only 1.6 million women of the target group got one or more smears in that period and 1.1 million women had no smears, corresponding to an average of 1.88 smears per woman. Conclusion Coverage reached only 59%, but the number of smears used was sufficient to cover more than 100% of the target population. Structural reduction of overuse and extension of coverage is warranted. [less ▲]

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See detailIntérêts et voies d'abord de la stadification paraaortique laparoscopique dans les cancers avances du col utérin
Kridelka, Frédéric ULiege; Goffin, Frédéric ULiege

in Revue Médicale de Liège (2007), 62 Spec No 2

The stage of a cervical neoplasm is defined on clinical criteria as reported by the International Federation of Gynecology and Obstetrics. Treatment planning however is based on this clinical stage, but ... [more ▼]

The stage of a cervical neoplasm is defined on clinical criteria as reported by the International Federation of Gynecology and Obstetrics. Treatment planning however is based on this clinical stage, but moreover on histological variables obtained at surgical staging. Regarding advanced stage cervical cancer, the recommanded treatment consists in a radical radiotherapy together with concomitant chemotherapy. The target volume of the radiation treatment is directly dependent on the paraaortic lymph node status, the radiological evaluation of which remains unsatisfactory due to lack of sensitivity. We report our experience with two laparoscopic approaches (transperitoneal and retroperitoneal) allowing a histological paraaortic nodal status to be obtained prior to initiating the definitive treatment. [less ▲]

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See detailExpression of matrix metalloproteinase-2 and mutant p53 is increased in hydatidiform mole as compared with normal placenta
Petignat, P.; Laurini, R.; Goffin, Frédéric ULiege et al

in International Journal of Gynecological Cancer (2006), 16(4, JUL-AUG), 1679-1684

Matrix metalloproteinases (MMPs) are group of enzymes thought to play an important role in trophoblastic and tumor invasion. The aim of our study was to investigate the trophoblastic expression of MMPs ... [more ▼]

Matrix metalloproteinases (MMPs) are group of enzymes thought to play an important role in trophoblastic and tumor invasion. The aim of our study was to investigate the trophoblastic expression of MMPs and p53 in normal trophoblast and hydatidiform moles (HM). Paraffin sections of 45 specimens, including 14 complete hydatidiform moles (CM), 15 partial hydatidiform moles (PM), 8 atypical partial hydatidiform moles (aPM), and 8 controls were selected. Classification of HM was established on histologic criteria and supported by the DNA ploidy results. Tissue sections from each case were immunostained with monoclonal antibodies, cytokeratin-7, MMP-2, MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1, and p53 wild type (p53wt) and mutant types (mutp53). Staining for cytokeratin-7 revealed a positive reaction in 93% of the samples. MMP-2 was mainly expressed in the syncytiotrophoblast of HM and found in 62% of aPM, 60% PM, and 93% CM. The mutp53 was mainly and focally expressed in syncytiotrophoblastic cells and was found in 63% of aPM, 80% PM, and 93% CM. Expression of MMP-2 and mutp53 was both significantly greater in HM vs control group (P < 0.05) and greater in CM vs PM and aPM (P < 0.05). No significant difference was observed for cytokeratin-7, MMP-9, TIMP-1, and p53wt between the HM subgroups and between HM and control group. MMP-2 and mutp53 are overexpressed in HM as compared with normal trophoblast and might participate in the invasive behavior of the HM. [less ▲]

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See detailShunting the intervillous space: New concepts in human uteroplacentat vascularization
Schaaps, Jean-Pierre ULiege; Tsatsaris, Vassilis; Goffin, Frédéric ULiege et al

in American Journal of Obstetrics and Gynecology (2005), 192(1), 323-332

Objective: It is supposed that the intervillous space. is not perfused by maternal blood during the first trimester, suggesting vascular shunts in the myometrium. We therefore attempted to provide ... [more ▼]

Objective: It is supposed that the intervillous space. is not perfused by maternal blood during the first trimester, suggesting vascular shunts in the myometrium. We therefore attempted to provide arguments for a functional vascular anastomotic network located in the placental bed during human pregnancy. Study design: Three-dimensional (3D) sonogyraphy, laboratory analyses. and anatomic studies (hysterectomy specimens, uteroplacental vascular cast) were performed. Results: Color Doppler showed a vascular network with anastomotic aspect located in the placental bed. A vascular cast of a uterus. obtained after postpartum hemorrhage. demonstrated a vascular anastomotic network in the myometrium. Higher Po-2 levels in the uterine vein compared with the intervillous space confirmed the functional nature of this Shunt. Low resistances in the uterine arteries during the first week after delivery suggested that this vascular network remains functional after placental expulsion. Conclusion: Our studies have yielded functional and anatomic evidence of an arteriovenous Shunt located in the subplacental myometrium. (C) 2005 Elsevier Inc. All rights reserved. [less ▲]

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See detailHuman chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium
PERRIER d'HAUTERIVE, Sophie ULiege; Charlet-Renard, Jeanne de Chantal ULiege; Berndt, Sarah ULiege et al

in Human Reproduction (2004), 19(11), 2633-2643

BACKGROUND: The elucidation of the molecular mechanisms by which the embryo contributes to its implantation is an area of extensive research. The main objective of this study was to investigate the ... [more ▼]

BACKGROUND: The elucidation of the molecular mechanisms by which the embryo contributes to its implantation is an area of extensive research. The main objective of this study was to investigate the pattern of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) secretion by human endometrial epithelium, and their regulation by human chorionic gonadotropin (hCG) and other growth factors present at the embryonic-endometrial interface. METHODS: Endometrial epithelial cells (EEC) were isolated from biopsies collected at both proliferative and secretory phases of fertile women. RESULTS: HCG (1-50 IU/ml) increased LIF secretion by EEC cultures derived from follicular phase (up to 285+/-75%) or from secretory phase (up to 212+/-16%). In contrast, hCG reduced IL-6 secretion by EEC in both phases. The hCG/LH receptor gene was transcribed by EEC as evidenced by RT-PCR. Insulin-like growth factors 1 and 2 increased LIF secretion by EEC. Transforming growth factor beta1 stimulated LIF and reduced IL-6 secretion. CONCLUSIONS: Through hCG, the blastocyst may be involved in the control of its implantation (via an increase of proimplantatory LIF) and tolerance (via an inhibition of proinflammatory IL-6). Other growth factors present at the embryonic-endometrial interface are also involved in the control of LIF and IL-6 endometrial secretion. [less ▲]

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See detailCirculating angiogenic factors and preeclampsia
Tsatsaris, V.; Goffin, Frédéric ULiege; Foidart, Jean-Michel ULiege

in New England Journal of Medicine (2004), 350(19), 2003-2004

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See detailOverexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: Pathophysiological consequences
Tsatsaris, V.; Goffin, Frédéric ULiege; Munaut, Carine ULiege et al

in Journal of Clinical Endocrinology and Metabolism (2003), 88(11), 5555-5563

Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in ... [more ▼]

Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development. [less ▲]

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See detailExpression pattern of metalloproteinases and tissue inhibitors of matrix-metalloproteinases in cycling human endometrium
Goffin, Frédéric ULiege; Munaut, Carine ULiege; Frankenne, Francis et al

in Biology of Reproduction (2003), 69(3), 976-984

The cyclic growth, differentiation, and cell death of endometrium represents the most dynamic example of steroid-driven tissue turnover in human adults. Key effectors in these processes-matrix ... [more ▼]

The cyclic growth, differentiation, and cell death of endometrium represents the most dynamic example of steroid-driven tissue turnover in human adults. Key effectors in these processes-matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs)-are regulated by ovarian steroids and, locally, by cytokines. We used reverse transcription-polymerase chain reaction to evaluate the expression of both transcriptionally regulated molecules such as estrogen receptor-alpha, progesterone receptor, and prolactin and a large array of MMPs and TIMPs (MMP-1, -2, -3, -7, -8, -9, -11, -12, -19, -26, MT1-MMP, MT2-MMP, MT3-MMP, TIMP-1, -2, -3). Altogether, three distinct patterns of MMP and two patterns of TIMP expression were detected in cycling endometrium: 1). MMPs restricted to the menstrual period (MMPs-1, -3, -8, -9, -12); 2). MMPs and TIMPs expressed throughout the cycle (MMP-2, MT1-MMP, MT2-MMP, MMP-19, TIMP-1, and TIMP-2); 3). MMPs predominantly expressed during the proliferative phase (MMP-7, MMP-11, MMP-26, and MT3-MMP); and 4). TIMP-3, which, contrary to the other TIMPs, shows significant modulations, with maximum expression during the late secretory and menstrual phases. These specific patterns of MMP expression associated with each phase of the cycle may point to specific roles in the processes of menstruation, housekeeping activities, angiogenesis, tissue growth, and extracellular matrix remodeling. [less ▲]

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See detailEvidence of a limited contribution of feto-maternal interactions to trophoblast differentiation along the invasive pathway
Goffin, Frédéric ULiege; Munaut, Carine ULiege; Malassine, A. et al

in Tissue Antigens (2003), 62(2), 104-116

Trophoblast differentiation is a key event in human placental development. During extravillous trophoblast (EVT) differentiation, stem cells from the anchoring villi detach from their basement membrane ... [more ▼]

Trophoblast differentiation is a key event in human placental development. During extravillous trophoblast (EVT) differentiation, stem cells from the anchoring villi detach from their basement membrane and proliferate to form aggregates called trophoblast cell columns (TCCs). They subsequently invade the decidua and differentiate into interstitial and endovascular trophoblasts. The influence of the decidua on EVT differentiation is controversial. We therefore compared the pattern of trophoblast differentiation marker expression in viable intrauterine and tubal pregnancies, as decidual cell markers (prolactin [PRL] and insulin-like growth factor binding Protein-1 [IGFBP1]) were only expressed in endometrial implantation sites. Extravillous trophoblast differentiation in anchoring villi from uterine and ectopic pregnancies exhibited a comparable phenotypical switch: alpha6 integrin subunit, E-cadherin, EGF receptor, Ki 67 and connexin 40 were localized in the proximal part of the TCC, while alpha5beta1 and alpha1 integrins, c-erb B2, hPL and HLA-G were expressed by invasive cytotrophoblasts. The cyclin-dependent kinase inhibitors p16 and p57 were mainly detected in invasive cytotrophoblasts some distance from the columns. However, the TCC was markedly longer in tubal pregnancy than in intrauterine pregnancy. These findings suggest that the decidua is not necessary to trigger EVT invasion, but that it is likely to limit the extent of the TCC and to accelerate the onset of EVT migration. [less ▲]

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