title: Clinical significance of Cyclin D1, FGF3 and p21 protein expression in laryngeal squamous cell carcinoma.
abstract: OBJECTIVE
  Laryngeal squamous cell carcinoma (LSCC) represents one of the most common cancers of the head and neck and the search for molecular markers is required for early diagnosis, prognosis and optimal therapy. The purpose of this study was to investigate the clinical significance of Cyclin D1, FGF3, p16 and p21 protein expression in LSCC and laryngeal dysplasia (LD) and to evaluate the associations between their expression levels and clinicopathological parameters of patients with LSCC.
  
  
  METHODS
  Immunohistochemistry was employed to detect and quantify the expression levels of Cyclin D1, FGF3, p16 and p21 in the laryngeal tissues of 48 LSCC patients, 32 patients with LD and 28 subjects with healthy laryngeal mucosa (HLM).
  
  
  RESULTS
  Significantly higher percentage of LSCC patients had positive Cyclin D1 expression compared with LD patients and HLM subjects (both p<0.01) and positive FGF3 expression than HLM subjects (p<0.05), while no differences in p16 and p21 positive expression were found among studied groups. The levels of Cyclin D1, FGF3 and p16 expression, as evaluated by immunostaining score, were significantly higher in patients with LSCC compared with LD and HLM groups (all p<0.05). Cyclin D1 proved to be highly sensitive and specific marker in differentiating LSCC from LD (sensitivity 81.2%, specificity 83.9%), while high sensitivity (81.2%) and lower specificity (41.4%) was observed in differentiating from HLM. Cyclin D1 and p21 expression levels were associated with regional lymph node metastases (both p<0.05) and Cyclin D1 expression levels significantly correlated with LSCC lymphatic invasion (x(2)=8.862; df=3; ?=0.031).
  
  
  CONCLUSIONS
  Cyclin D1, FGF3 and p16 are overexpressed in patients with LSCC. Cyclin D1 is a highly sensitive marker in differentiating LSCC from LD or HLM. Cyclin D1 and p21 expression levels may be useful as predictive markers of metastases in LSCC.
authors.affiliation: 1Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors.forename: Ivan P
authors.initials: IP
authors.lastname: Jovanovic
authors.forename: Gordana D
authors.initials: GD
authors.lastname: Radosavljevic
authors.forename: Bojana J
authors.initials: BJ
authors.lastname: Simovic-Markovic
authors.forename: Stevan P
authors.initials: SP
authors.lastname: Stojanovic
authors.forename: Srdjan M
authors.initials: SM
authors.lastname: Stefanovic
authors.forename: Nada N
authors.initials: NN
authors.lastname: Pejnovic
authors.forename: Nebojsa N
authors.initials: NN
authors.lastname: Arsenijevic
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005260:Female; D051518:Fibroblast Growth Factor 3 / Q000378:metabolism*; D006258:Head and Neck Neoplasms; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3; D019938:Cyclin D1