title: Podoplanin Expression in Cancer-associated Fibroblasts Predicts Poor Prognosis in Patients with Squamous Cell Carcinoma of the Lung.
abstract: Podoplanin is a candidate cancer stem cell marker in squamous cell carcinoma (SCC). Several studies have reported the prognostic value of podoplanin expression in tumor cells in lung SCC but few have focused on its expression in cancer-associated fibroblasts (CAFs). The aim of this study was to analyze the prognostic significance of podoplanin expression, with special reference to the expression pattern in both tumor cells and CAFs.
  
  
  
  Immunohistochemical analyses using anti-podoplanin antibody were performed on 126 resected specimens of lung SCC. When more than 10% of tumor cells or CAFs showed immunoreactivity with podoplanin levels as strong as those of the positive controls, the specimens were classified as a podoplanin-positive.
  
  
  
  Podoplanin-positive status in tumor cells (n=54) was correlated with a lower incidence of lymphatic invasion (p=0.031) but there were no significant differences in disease-free survival (DFS) and disease-specific survival (DSS) by the log-rank test. Podoplanin-positive status in CAFs (n=41) was correlated with more advanced stage (p=0.008), higher frequency of pleural invasion (p=0.002) and both shorter DFS (p=0.006) and DSS (p=0.006). In Cox's multivariate analysis, podoplanin-positive status in CAFs was an independent negative prognostic factor for DFS (p=0.027) and DSS (p=0.027).
  
  
  
  Podoplanin expression in CAFs might be an independent unfavorable prognostic indicator in patients with lung SCC, irrespective of the expression status of tumor cells.
authors.affiliation: Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.|Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yurugi
authors.affiliation: Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.|Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Wakahara
authors.affiliation: Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.|Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsuoka
authors.affiliation: Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sakabe
authors.affiliation: Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.|Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kubouchi
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Haruki
authors.affiliation: Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Nosaka
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Miwa
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Araki
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Shiomi
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Tottori, Japan yume@med.tottori-u.ac.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Umekita
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011379:Prognosis; D000098853:Podoplanin
chemical_list: D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: Podoplanin; immunohistochemistry; lung; squamous cell carcinoma