title: STAT3 is a key pathway in primary intraosseous squamous cell carcinoma arising from an odontogenic keratocyst.
abstract: OBJECTIVE
  Primary intraosseous squamous cell carcinoma (PIOSCC) arising within an odontogenic keratocyst (OKC) is rare malignancy, entailing a poor prognosis for delayed diagnosis. The number of reports concerning this entity is extremely small. The aim of this study is to present the clinical and pathologic characteristics of PIOSCC and investigate its pathogenesis.
  
  
  METHODS
  This study describes three patients with mandibular PIOSCC derived from an OKC over a seven-year period, each of which suffering from decompression in mandible. Important diagnostic criteria included the absence of overlying oral mucosal ulceration, the absence of a distant potential primary tumor, and the presence of a completely intraosseus lesion. The malignant transformation of OKC to PIOSCC was confirmed by pathologic evaluation of surgical resection specimens. Immunohistochemistry (IHC) was used to evaluating expression of Ki-67, p65, EGFR, phospho-AKT, and STAT3 in each of the three tumors and adjacent cyst walls.
  
  
  RESULTS
  Analysis by IHC indicated that Ki67, P65, EGFR and STAT3 were substantially elevated in PIOSCC. There was an obvious positive correlation between Ki67, P65, EGFR and STAT3 expression in adjacent benign epithelium. Each tumor exhibited long-standing chronic inflammation in the benign odontogenic cyst, suggesting that a sustained immune response may be partially responsible for malignant transformation of the benign cystic lining cells.
  
  
  CONCLUSIONS
  These findings indicate that inflammation may be the principal mediator in PIOSCC ex-OKC, and the STAT3 signaling pathway is an important contributor to this process. Combined detection of Ki67, P65, and EGFR in the lesional epithelium can support the diagnosis of PIOSCC.
authors.affiliation: Department of Oral-Maxilla Head and Neck Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Shanghai 200011, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oral-Maxilla Head and Neck Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Shanghai 200011, P.R. China.
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Liu
authors.affiliation: Department of Oral-Maxilla Head and Neck Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology Shanghai 200011, P.R. China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Ye
authors.affiliation: Laboratory of Molecular Neuropharmacology, School of Pharmacy East China University of Science and Technology 130 Meilong Road, Shanghai 200237, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
keywords: Primary intraosseous squamous cell carcinoma; STAT3; decompression; inflammation; odontogenic keratocyst