title: Combining Cadherin Expression with Molecular Markers Discriminates Invasiveness in Growth Hormone and Prolactin Pituitary Adenomas.
abstract: Although growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, whereas N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, β-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion.
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: N
authors.initials: N
authors.lastname: Chauvet
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: N
authors.initials: N
authors.lastname: Romanò
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: A-C
authors.initials: AC
authors.lastname: Meunier
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: E
authors.initials: E
authors.lastname: Galibert
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Fontanaud
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: M-N
authors.initials: MN
authors.lastname: Mathieu
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Osterstock
authors.affiliation: Service de Médecine Légale, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Osterstock
authors.affiliation: Service de Médecine Légale, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France.
authors.forename: E
authors.initials: E
authors.lastname: Baccino
authors.affiliation: Laboratoire d'Anatomie et Cytologie Pathologiques, Hôpital Gui de Chauliac, CHU Montpellier, Montpellier, France.
authors.forename: V
authors.initials: V
authors.lastname: Rigau
authors.affiliation: Service de Neurochirurgie, CHU Bordeaux, Site Pellegrin, Université de Bordeaux, Bordeaux, France.
authors.forename: H
authors.initials: H
authors.lastname: Loiseau
authors.affiliation: Service de Pathologie, CHU Bordeaux, Site Pellegrin, Université de Bordeaux, Bordeaux, France.
authors.forename: S
authors.initials: S
authors.lastname: Bouillot-Eimer
authors.affiliation: Faculté de Médecine, CRN2M-UMR 7286, CNRS, Université Aix-Marseille, Marseille, France.|Laboratoire de Biologie Moléculaire, AP-HM, Hôpital de la Conception, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Barlier
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Mollard
authors.affiliation: UMR-5203, CNRS, Institut de Génomique Fonctionnelle, Montpellier, France.|U1191, INSERM, Montpellier, France.|UMR-5203, Université de Montpellier, Montpellier, France.
authors.forename: N
authors.initials: N
authors.lastname: Coutry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D037502:Galectin 3 / Q000096:biosynthesis*; D037161:Galectins; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D015175:Prolactinoma / Q000378:metabolism / Q000473:pathology*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D064249:Securin / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D015820:Cadherins; C539364:ESRP1 protein, human; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; D016601:RNA-Binding Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human
keywords: ESRP1; binary tree analysis; cadherins; epithelial mesenchymal transition; human pituitary tumours