6533b7d5fe1ef96bd12638eb
RESEARCH PRODUCT
TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma
Russo AntonioCorsale SimonaAgnese ValentinaMacaluso MarcellaCascio SandraBruno LoredanaSurmacz EvaDardanoni GabriellaValerio Maria RosariaVieni SalvatoreRestivo SalvatoreFulfaro FabioTomasino Rosa MariaGebbia NicolaBazan Vivianasubject
squamous cell carcinomasingle strand conformation polymorphismPrognosipolymerase chain reactionDNA Mutational AnalysisEMTREE drug terms: protein p53 EMTREE medical terms: advanced cancerS PhaseDNA Mutational AnalysiHumansprotein p53 advanced cancer; article; cell cycle S phase; DNA content; exon; flow cytometry; follow up; gene; gene mutation; genetic analysis; histopathology; human; human tissue; larynx carcinoma; multivariate analysis; ploidy; polymerase chain reaction; priority journal; prospective study; single strand conformation polymorphism; squamous cell carcinoma; tp53 gene Carcinoma Squamous Cell; DNA Mutational Analysis; DNA Neoplasm; Genes ras; Humans; Laryngeal Neoplasms; Mutation; Ploidies; Polymorphism Single-Stranded Conformational; Prognosis; S Phase; Survival Rate; Tumor Suppressor Protein p53 [EMTREE drug terms]follow uplarynx carcinomatp53 gene MeSH: Carcinoma Squamous Cellexongene mutationhumanmultivariate analysigeneLaryngeal NeoplasmsPolymorphism Single-Stranded ConformationalLaryngeal NeoplasmPloidiesflow cytometryarticleploidyDNA NeoplasmPrognosisGenes rahuman tissueSurvival RateGenes rascell cycle S phasepriority journalDNA contentgenetic analysiMutationCarcinoma Squamous CellhistopathologyTumor Suppressor Protein p53Ploidieprospective studydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-06-21 |