title: Podoplanin: a novel marker for oral cancer risk in patients with oral premalignancy.
abstract: OBJECTIVE
  Oral leukoplakia (OPL) is a heterogeneous oral lesion with an increased oral cancer risk. Current clinical parameters cannot predict the potential of malignant transformation in patients with OPL. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in oral cancer and some oral premalignancies. The purpose of this study is to determine a role of podoplanin in predicting oral cancer development in patients with OPL.
  
  
  METHODS
  Podoplanin expression was determined in 150 OPL patients with long-term follow-up using immunohistochemistry. Association between the protein expression patterns and clinicopathologic parameters including oral cancer development during the follow-up were analyzed.
  
  
  RESULTS
  Fifty-six (37%) of the 150 OPL patients exhibited podoplanin expression in the basal and suprabasal layers and were classified as podoplanin positive. Podoplanin positivity was more frequent in older patients (P = .016), females (P = .020), and dysplastic lesions (P = .040). Patients with OPL that was podoplanin positive had significantly higher incidence of oral cancer than did those whose OPL was podoplanin negative (P = .0002). In the multivariate analysis using histology and podoplanin as cofactors, podoplanin was the only independent factor for oral cancer development (hazard ratio = 3.087; 95% CI, 1.530 to 6.231; P = .002). Importantly, oral cancer risk can be further stratified by considering both histology and podoplanin information.
  
  
  CONCLUSIONS
  Podoplanin is frequently expressed in OPL. Together with histology, podoplanin may serve as a powerful biomarker to predict the risk for oral cancer development in patients with OPL.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Vali
authors.initials: V
authors.lastname: Papadimitrakopoulou
authors.forename: Hening
authors.initials: H
authors.lastname: Ren
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Fan
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Edward
authors.initials: E
authors.lastname: Kim
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Li
authors.initials: L
authors.lastname: Mao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D015854:Up-Regulation; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin