TP53 Mutations and S-Phase Fraction but not DNA-Ploidy Are Independent Prognostic Indicators in Laryngeal Squamous Cell Carcinoma

ToprospectivelyevaluatetheprognosticsignificanceofTP53,H-,K-,andN-Rasmutations,DNA-ploidyandS-phasefraction(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 byflow 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 triplemutations.Intotal,46TP53mutationswereobserved.Themajority(41%)oftheseoccurinexon5(19/46),whilethemutations inexons6,7,and8wererepresentedin14,7,and6patients,respectively(31%,15%,and16%).FiveLSCCpatients(6%)showeda mutation in H-Ras gene. Sixty-three percent of the cases (51/81) were DNA aneuploidy, 14% of these (7/51) were multiclonal. Thirty-ninepatients(48%)hadanhighSPFvalue.AtUnivariateanalysis,theDNAaneuploidy,highSPF(>15.1%),TP53mutations 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 importantbiologicalindicatorstopredicttheoutcomeofLSCCpatients. J.Cell.Physiol.206:181‐188,2006.2005Wiley-Liss,Inc.