title: Induction of epithelial-mesenchymal transition and loss of podoplanin expression are associated with progression of lymph node metastases in human papillomavirus-related oropharyngeal carcinoma.
abstract: OBJECTIVE
  To examine human papillomavirus (HPV) status, the expression of podoplanin and epithelial-mesenchymal transition (EMT) markers and lymphatic vessel counts (LVC) in oropharyngeal squamous cell carcinoma (OPSCC) tissues, and to evaluate whether these factors were associated with survival and nodal status.
  
  
  RESULTS
  A total of 53 OPSCC specimens were evaluated for HPV status and expression of proteins such as podoplanin and EMT markers by immunohistochemistry. E-cadherin-negative and vimentin-positive specimens were defined as EMT-positive. Twenty-two OPSCCs were HPV-positive. There was significant progression of nodal status in patients with HPV-positive tumours (P = 0.0475). HPV-positive cases had significantly lower expression of podoplanin (P = 0.0016) and were more frequently EMT-positive (P = 0.0172). Podoplanin-negative cases and EMT-positive cases showed significantly more advanced nodal status than their respective counterparts (P = 0.0082 and P = 0.0186, respectively). LVC correlated with neither HPV nor nodal status. Multivariate analyses revealed that HPV infection was an independent marker of longer disease-specific survival (P = 0.014).
  
  
  CONCLUSIONS
  HPV-positivity in OPSCC was associated with loss of podoplanin expression and with EMT induction, which resulted in progression of nodal status. The mechanisms leading to an improved prognosis in HPV-positive OPSCC patients requires elucidation, as this is inconsistent with the aggressive phenotype with lymph node metastases.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wakisaka
authors.forename: Shinya
authors.initials: S
authors.lastname: Yoshida
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.forename: Makiko
authors.initials: M
authors.lastname: Kita
authors.forename: Seiko
authors.initials: S
authors.lastname: Sawada-Kitamura
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Endo
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuji
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakanish
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Murono
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications*; D000077195:Squamous Cell Carcinoma of Head and Neck; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: epithelial-mesenchymal transition; human papillomavirus; lymph node metastasis; oropharyngeal cancer; podoplanin