title: Significance of nuclear p-mTOR expression in advanced oral squamous cell carcinoma with extracapsular extension of lymph node metastases.
abstract: OBJECTIVE
  Traditional dichotomous extranodal extension (ENE) grading could not differentiate the risk of subsequent failure in advanced stage oral squamous cell carcinoma (OSCC) patients with ENE. This study investigated nuclear phosphorylated mammalian target of rapamycin (p-mTOR) expression in extranodal tumours and correlated this with clinical outcomes.
  
  
  METHODS
  A total of 218 advanced stage OSCC patients with neck lymph node metastasis were enrolled. Paired paraffin-embedded primary tumour and metastatic lymph node sections were stained with antibody against p-mTOR. Tumours with moderate-to-strong staining in ≧50% of tumour cells were recorded as being positive p-mTOR expression. The correlation of nuclear p-mTOR expression in extranodal tumours with clinicopathologic parameters was analysed.
  
  
  RESULTS
  Nuclear p-mTOR expression in primary and extranodal tumours was highly associated with a lower grade of differentiation. The 5-year disease-free survival (DFS) of the patients without ENE, with and without positive nuclear p-mTOR expression in extranodal tumours was 54.3%, 23.4% and 55.2%, respectively. The 5-year overall survival (OS) of the patients without ENE, with and without nuclear p-mTOR expression in extranodal tumours was 55%, 18.7% and 51.3%, respectively. The patients with nuclear p-mTOR expression in extranodal tumours had significantly worse regional and distant disease control. Multivariate analysis also confirmed that nuclear p-mTOR expression in extranodal tumours was a significant independent adverse factor.
  
  
  CONCLUSIONS
  Nuclear p-mTOR expression can be used as a prognostic indicator predictive of DFS and OS in advanced OSCC patients with ENE. There might be a possibility for targeted therapy in this group of patients.
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Department of Otolaryngology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin 640, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Tseng-Cheng
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Chen-Tu
authors.initials: CT
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Lou
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Jenq-Yuh
authors.initials: JY
authors.lastname: Ko
authors.affiliation: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan. Electronic address: ntuhylc@gmail.com.
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Disease-free survival; Extranodal extension; Extranodal tumour; Metastatic lymph node; Oral squamous cell carcinoma; Overall survival; Phospho–mammalian target of rapamycin; Recurrence