title: Tumorigenic factor CRIPTO-1 is immunolocalized in extravillous cytotrophoblast in placenta creta.
abstract: CRIPTO-(CR)1 is a protein associated with tumorigenesis and metastasis. Here we demonstrate that CR-1 expression in normal and creta placentas is associated with various degrees of uterine invasion. Cytokeratin (CK) and CR-1 protein expression was visualized by immunohistochemical staining of formalin-fixed, paraffin-embedded placental specimens (control placentas, n = 9; accreta, n = 6; increta, n = 10; percreta, n = 15). The pattern of extravillous trophoblast (EVT) cell morphology was distinctive in creta placentas: densely-compacted cell columns and large star-shaped cells with a typically migratory phenotype, not common among third trimester control placentas. Quantification revealed higher CR-1 immunoreactivities in accreta (P = 0.001), increta (P = 0.0002), and percreta placentas (P = 0.001) than in controls. In contrast to controls, there was a significant positive relationship between CR-1 and CK reactivity in all creta placentas (accreta, P = 0.02; increta, P = 0.0001, and percreta, P = 0.025). This study demonstrated CR-1 expression in the placental bed, its increased expression in creta placentas, and EVT cells as the main CR-1-producing cell type. Morphological examination revealed an immature and invasive trophoblast profile in creta placentas, suggesting impairment of the trophoblast differentiation pathway. These findings provide important new insights into the pathophysiology of abnormal creta placentation and its gestational consequences.
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, No. 1524, Cidade Universitária, 05508-900 São Paulo, SP, Brazil.
authors.forename: Carla Letícia
authors.initials: CL
authors.lastname: Bandeira
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, No. 1524, Cidade Universitária, 05508-900 São Paulo, SP, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Urban Borbely
authors.affiliation: Department of Obstetrics, Clinics Hospital, School of Medicine, University of São Paulo, Avenida Dr. Enéas de Carvalho Aguiar, No. 255, Cerqueira César, 05403-000 São Paulo, SP, Brazil.
authors.forename: Rossana
authors.initials: R
authors.lastname: Pulcineli Vieira Francisco
authors.affiliation: Division of Pathology, Clinics Hospital, School of Medicine, University of São Paulo, Avenida Dr. Enéas de Carvalho Aguiar, No. 255, Cerqueira César, 05403-000 São Paulo, SP, Brazil.
authors.forename: Regina
authors.initials: R
authors.lastname: Schultz
authors.affiliation: Department of Obstetrics, Clinics Hospital, School of Medicine, University of São Paulo, Avenida Dr. Enéas de Carvalho Aguiar, No. 255, Cerqueira César, 05403-000 São Paulo, SP, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Zugaib
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, No. 1524, Cidade Universitária, 05508-900 São Paulo, SP, Brazil.
authors.forename: Estela
authors.initials: E
authors.lastname: Bevilacqua
mesh_terms: D000328:Adult; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011247:Pregnancy / Q000378:metabolism*; D011263:Pregnancy Trimester, Third / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*
chemical_list: D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human