PMID- 15965904 OWN - NLM STAT- MEDLINE DCOM- 20060317 LR - 20051103 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 206 IP - 1 DP - 2006 Jan TI - TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma. PG - 181-8 AB - 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. CI - Copyright 2005 Wiley-Liss, Inc. FAU - Russo, Antonio AU - Russo A AD - Section and Oncology, Department of Oncology, Universita di Palermo, Palermo, Italy. lab-oncobiologia@usa.net FAU - Corsale, Simona AU - Corsale S FAU - Agnese, Valentina AU - Agnese V FAU - Macaluso, Marcella AU - Macaluso M FAU - Cascio, Sandra AU - Cascio S FAU - Bruno, Loredana AU - Bruno L FAU - Surmacz, Eva AU - Surmacz E FAU - Dardanoni, Gabriella AU - Dardanoni G FAU - Valerio, Maria Rosaria AU - Valerio MR FAU - Vieni, Salvatore AU - Vieni S FAU - Restivo, Salvatore AU - Restivo S FAU - Fulfaro, Fabio AU - Fulfaro F FAU - Tomasino, Rosa Maria AU - Tomasino RM FAU - Gebbia, Nicola AU - Gebbia N FAU - Bazan, Viviana AU - Bazan V LA - eng PT - Journal Article PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (DNA, Neoplasm) RN - 0 (Tumor Suppressor Protein p53) SB - IM MH - Carcinoma, Squamous Cell/*diagnosis/*genetics/pathology MH - DNA Mutational Analysis MH - DNA, Neoplasm MH - Genes, ras MH - Humans MH - Laryngeal Neoplasms/*diagnosis/*genetics/pathology MH - Mutation MH - *Ploidies MH - Polymorphism, Single-Stranded Conformational MH - Prognosis MH - S Phase/*physiology MH - Survival Rate MH - Tumor Suppressor Protein p53/*genetics EDAT- 2005/06/21 09:00 MHDA- 2006/03/18 09:00 CRDT- 2005/06/21 09:00 PHST- 2005/06/21 09:00 [pubmed] PHST- 2006/03/18 09:00 [medline] PHST- 2005/06/21 09:00 [entrez] AID - 10.1002/jcp.20447 [doi] PST - ppublish SO - J Cell Physiol. 2006 Jan;206(1):181-8. doi: 10.1002/jcp.20447.