title: The spectrum of podoplanin expression in encapsulating peritoneal sclerosis.
abstract: Encapsulating peritoneal sclerosis (EPS) is a life threatening complication of peritoneal dialysis (PD). Podoplanin is a glycoprotein expressed by mesothelial cells, lymphatic endothelial cells, and myofibroblasts in peritoneal biopsies from patients with EPS. To evaluate podoplanin as a marker of EPS we measured podoplanin mRNA and described the morphological patterns of podoplanin-positive cells in EPS. Included were 20 peritoneal biopsies from patients with the diagnosis of EPS (n = 5), patients on PD without signs of EPS (n = 5), and control patients (uremic patients not on PD, n = 5, non-uremic patients n = 5). EPS patient biopsies revealed significantly elevated levels of podoplanin mRNA (p<0.05). In 24 peritoneal biopsies from patients with EPS, podoplanin and smooth muscle actin (SMA) were localized by immunohistochemistry. Four patterns of podoplanin distribution were distinguishable. The most common pattern (8 of 24) consisted of organized, longitudinal layers of podoplanin-positive cells and vessels in the fibrotic zone ("organized" pattern). 7 of 24 biopsies demonstrated a diffuse distribution of podoplanin-positive cells, accompanied by occasional, dense clusters of podoplanin-positive cells. Five biopsies exhibited a mixed pattern, with some diffuse areas and some organized areas ("mixed"). These contained cuboidal podoplanin-positive cells within SMA-negative epithelial structures embedded in extracellular matrix. Less frequently observed was the complete absence of, or only focal accumulations of podoplanin-positive fibroblasts outside of lymphatic vessels (podoplanin "low", 4 of 24 biopsies). Patients in this group exhibited a lower index of systemic inflammation and a longer symptomatic period than in EPS patients with biopsies of the "mixed" type (p<0.05). In summary we confirm the increased expression of podoplanin in EPS, and distinguish EPS biopsies according to different podoplanin expression patterns which are associated with clinical parameters. Podoplanin might serve as a useful adjunct to the morphological workup of peritoneal biopsies.
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine and Nephrology, Robert-Bosch-Hospital, Stuttgart, Germany.
authors.forename: Niko
authors.initials: N
authors.lastname: Braun
authors.forename: M Dominik
authors.initials: MD
authors.lastname: Alscher
authors.forename: Peter
authors.initials: P
authors.lastname: Fritz
authors.forename: Joerg
authors.initials: J
authors.lastname: Latus
authors.forename: Ilka
authors.initials: I
authors.lastname: Edenhofer
authors.forename: Fabian
authors.initials: F
authors.lastname: Reimold
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.forename: Martin
authors.initials: M
authors.lastname: Kimmel
authors.forename: Dagmar
authors.initials: D
authors.lastname: Biegger
authors.forename: Maja
authors.initials: M
authors.lastname: Lindenmeyer
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D056627:Peritoneal Fibrosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D000199:Actins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C117468:PDPN protein, human; D000098853:Podoplanin