title: Cyclin D1, EGFR, and Akt/mTOR pathway. Potential prognostic markers in localized laryngeal squamous cell carcinoma.
abstract: BACKGROUND
  EGFR (epidermal growth factor receptor), cyclin D1 and Akt/mTOR pathways are active in head and neck cancer. The aim of this study was to explore biomarker expression, their correlations with clinicopathological parameters and their prognostic utility in a cohort of patients with localized squamous laryngeal carcinoma.
  
  
  METHODS
  We assessed relative messenger RNA expression of EGFR, Akt1, 2, and 3, mTOR and CCND1, copy number variants of the EGFR and CCND1 genes and immunohistochemical protein expression of EGFR, p-Akt308, p-Akt473, pmTOR, PTEN, p53 and cyclin D1 in paraffin-embedded tissue samples of localized laryngeal carcinomas.
  
  
  RESULTS
  In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumors of the larynx, high EGFR and CCND1 mRNA correlated with no or ex-smoking, (p = 0.003 and p = 0.029, respectively), while low Akt3 mRNA correlated with alcohol abuse, N0 stage, total laryngectomy, and absence of neck dissection. At a median follow-up of 74.5 months, high mTOR mRNA expression was marginally associated with shorter disease-free survival (hazard ratio [HR] = 1.54; p = 0.093) and high Akt3 mRNA with shorter overall survival (HR = 1.49; p = 0.0786), in univariate analysis. In multivariate analysis, node-positive status, subglottic-transglottic location, surgery other than total laryngectomy and mTOR/CCND1 mRNA interaction with a hazard ratio of 2.16 (p value for interaction:  0.0010) were independent predictors of relapse, while node-positive status and subglottic-transglottic location were associated with higher risk for death.
  
  
  CONCLUSIONS
  In localized laryngeal cancer, clinicopathological parameters and an interaction of high mTOR and CCND1 mRNA expression were found to be associated with poor patient outcome.
authors: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Peripheriaki odos, Nea Efkarpia, 56403, Thessaloniki, Greece. dimitris.dionysopoulos@gmail.com
authors: D
authors: D
authors: Dionysopoulos
authors: K
authors: K
authors: Pavlakis
authors: V
authors: V
authors: Kotoula
authors: E
authors: E
authors: Fountzilas
authors: K
authors: K
authors: Markou
authors: I
authors: I
authors: Karasmanis
authors: N
authors: N
authors: Angouridakis
authors: A
authors: A
authors: Nikolaou
authors: K T
authors: KT
authors: Kalogeras
authors: G
authors: G
authors: Fountzilas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D012333:RNA, Messenger; D019938:Cyclin D1; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases
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