title: TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma.
abstract: To prospectively evaluate the prognostic significance of TP53, H-, K-, and N-Ras mutations, DNA-ploidy and S-phase fraction (SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed by flow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triple mutations. In total, 46 TP53 mutations were observed. The majority (41%) of these occur in exon 5 (19/46), while the mutations in exons 6, 7, and 8 were represented in 14, 7, and 6 patients, respectively (31%, 15%, and 16%). Five LSCC patients (6%) showed a mutation in H-Ras gene. Sixty-three percent of the cases (51/81) were DNA aneuploidy, 14% of these (7/51) were multiclonal. Thirty-nine patients (48%) had an high SPF value. At Univariate analysis, the DNA aneuploidy, high SPF (>15.1%), TP53 mutations and, in particular, the mutations that occur in exons 5 and 8 were significantly related to quicker disease relapse and short OS. At Multivariate analysis, the major significant predictors for both disease relapse and death were high SPF and any TP53 mutations. While histological grade G3 was an independent factor only for relapse. In conclusions, any TP53 mutations and high SPF are important biological indicators to predict the outcome of LSCC patients.
authors.affiliation: Section and Oncology, Department of Oncology, Università di Palermo, Palermo, Italy. lab-oncobiologia@usa.net
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Simona
authors.initials: S
authors.lastname: Corsale
authors.forename: Valentina
authors.initials: V
authors.lastname: Agnese
authors.forename: Marcella
authors.initials: M
authors.lastname: Macaluso
authors.forename: Sandra
authors.initials: S
authors.lastname: Cascio
authors.forename: Loredana
authors.initials: L
authors.lastname: Bruno
authors.forename: Eva
authors.initials: E
authors.lastname: Surmacz
authors.forename: Gabriella
authors.initials: G
authors.lastname: Dardanoni
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Valerio
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vieni
authors.forename: Salvatore
authors.initials: S
authors.lastname: Restivo
authors.forename: Fabio
authors.initials: F
authors.lastname: Fulfaro
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Tomasino
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm; D011905:Genes, ras; D006801:Humans; D007822:Laryngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D011003:Ploidies; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D016196:S Phase / Q000502:physiology*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53