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.

Significance of new membrane formation in peritoneal biopsies of peritoneal dialysis patients: a case–control study

“…Braun et al first reported that the presence podoplaninpositive fibroblast-like cells was a good marker of EPS [11,12]. Podoplanin was first described as a molecule expressed on glomerular podocytes [27] and was later was found to be a useful marker of lymphatic endothelial [28] and mesothelial cells [29].…”

“…Macroscopic findings of abdominal organs suggested a newly formed encapsulating membrane, mainly in the visceral peritoneum, was unique to EPS [10]. Histologically, the structure of encapsulating membrane was described as organized fibrosing tissue formed on the peritoneal membrane proper with swollen fibroblast-like cells immunohistochemically positive for podoplanin [11,12]. These observations suggested that a definite pathological diagnosis of EPS requires macroscopic and/or histological confirmation of an encapsulating membrane.…”

Platelet-Derived Growth Factor Receptor-β Expression in Human Peritoneum

“…We have previously described a population of podoplanin-positive cells in peritoneal biopsies from patients with EPS [3,4]. These cells coexpress smooth-muscle actin (SMA; a marker of myofibroblasts) and podoplanin.…”

“…We demonstrated that 15 of 18 biopsies from patients with EPS demonstrated a diffuse accumulation of podoplanin-positive cells [3], whereas these cells were focally present in 3 of 16 specimens from PD patients without signs of EPS, and in none of the 35 controls [3]. Podoplanin-positive cells appear in four morphological patterns [4]. An organized pattern was found in 8 of 24 biopsies, with longitudinal layers of podoplanin-positive cells, a diffuse pattern (in 7 of 24 biopsies) with a random and at times dense podoplanin-positive cell accumulation, and a combination of those two patterns (‘mixed' in 5 of 24 biopsies) [4].…”

“…Podoplanin-positive cells appear in four morphological patterns [4]. An organized pattern was found in 8 of 24 biopsies, with longitudinal layers of podoplanin-positive cells, a diffuse pattern (in 7 of 24 biopsies) with a random and at times dense podoplanin-positive cell accumulation, and a combination of those two patterns (‘mixed' in 5 of 24 biopsies) [4]. As in the previous study, in biopsies of some patients, an accumulation of podoplanin-positive myofibroblasts was not present, but only expression by lymphatic endothelial cells (4 of 24 biopsies, podoplanin ‘low') [4].…”