title: Enhanced apoptosis correlates with poor survival in patients with laryngeal cancer but not with cell proliferation, bcl-2 or p53 expression.
abstract: The purpose of the current study was to analyse apoptosis and bcl-2 expression in laryngeal squamous cell carcinoma (SCC) with special reference to their prognostic significance, correlation with the clinical and pathological characteristics as well as cell proliferation and p53 accumulation. 172 patients with primary laryngeal SCC were followed-up for a median of 67 months. The volume corrected apoptotic (A/V) index was analysed using an in situ end labelling method (TUNEL) in 85 randomly selected patients. The expression of bcl-2 and p53 was analysed with monoclonal antibodies. The proliferative activity was measured both with Ki-67 (MIB-1) antibody and the volume corrected mitotic (M/V) index. The A/V index was not associated with p53 (P = 0.6) or bcl-2 (P = 0.6) expression or with proliferative parameters (P = 0.9 for M/V and P = 0.3 for MIB-1). The 10-year overall survival in patients with a high A/V index was poorer when compared with patients with a low index (47% versus 81%, P = 0.005), while accumulation of bcl-2 had no prognostic significance (P = 0.5). In Cox multivariate analysis of the whole cohort, stage (P < 0.0005) and histological grade (P = 0.04) were predictors of overall survival. In the subset of patients with an A/V index available, predictors of survival were stage (P = 0.05), A/V index (P = 0.02) and histological grade (P = 0.04). A high A/V index was an independent predictor of poor survival in laryngeal SCC. This effect was not associated with tumour cell proliferation. Accumulations of p53 and bcl-2 were not associated with apoptosis. Expression of bcl-2 lacks any prognostic significance in laryngeal SCC. We propose that assessment of the A/V index may help in selecting patients with poor prognosis.
authors.affiliation: Department of Oncology, Tampere University Hospital, Finland. pasi.hirvikoski@uku.fi
authors.forename: P
authors.initials: P
authors.lastname: Hirvikoski
authors.forename: E
authors.initials: E
authors.lastname: Kumpulainen
authors.forename: J
authors.initials: J
authors.lastname: Virtaniemi
authors.forename: R
authors.initials: R
authors.lastname: Pirinen
authors.forename: L
authors.initials: L
authors.lastname: Salmi
authors.forename: P
authors.initials: P
authors.lastname: Halonen
authors.forename: R
authors.initials: R
authors.lastname: Johansson
authors.forename: V M
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002455:Cell Division; D015331:Cohort Studies; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis