title: Abnormalities of molecular regulators of proliferation and apoptosis in carcinoma of the oral cavity and oropharynx.
abstract: OBJECTIVE
  Abnormalities in genes regulating cell proliferation and death may affect disease outcome in squamous cell carcinoma (SCC) of the head and neck.
  
  
  METHODS
  Proliferative activity (Histone H3 in-situ-hybridization (HISH) labeling index (LI)) and the genes and/or gene products of Cyclin D-1, c-erbB-2, Bcl-2, p21, and p53, were investigated in 35 patients with SCC of the oral cavity and oropharynx, previously studied for p27 expression.
  
  
  RESULTS
  Overexpression or very low expression of Cyclin D-1 was associated with unfavorable disease outcome and shorter time-to-recurrence. High c-erbB-2 expression was significantly associated with shorter overall survival and was synergistic with low p27 expression. Bcl-2, HISH LI, p21 expression, and p53 mutation and protein analysis were not significantly predictive, but there were trends suggesting shorter disease-free/overall survival for patients with undetectable Bcl-2, high HISH, and mutant p53.
  
  
  CONCLUSIONS
  Several cell proliferation and death regulators appeared to predict disease outcome. Limited evidence of cooperativeness among regulators was also seen.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Philipps University, Deutschhausstr. 3, 35037, Marburg, Germany. kuropkat@hno-marburg.de
authors.forename: Christiane
authors.initials: C
authors.lastname: Kuropkat
authors.forename: T K
authors.initials: TK
authors.lastname: Venkatesan
authors.forename: D D
authors.initials: DD
authors.lastname: Caldarelli
authors.forename: W R
authors.initials: WR
authors.lastname: Panje
authors.forename: J
authors.initials: J
authors.lastname: Hutchinson
authors.forename: H D
authors.initials: HD
authors.lastname: Preisler
authors.forename: J S
authors.initials: JS
authors.lastname: Coon
authors.forename: J A
authors.initials: JA
authors.lastname: Werner
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D019938:Cyclin D1 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D009959:Oropharyngeal Neoplasms / Q000737:chemistry* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006657:Histones; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human