TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma

Antonio Russo, Simona Corsale, Valentina Agnese, Marcella Macaluso, Sandra Cascio, Loredana Bruno, Eva Surmacz, Gabriella Dardanoni, Maria Rosaria Valerio, Salvatore Vieni, Salvatore Restivo, Fabio Fulfaro, Rosa Maria Tomasino, Nicola Gebbia, Viviana Bazan

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)181-188
Number of pages8
JournalJournal of Cellular Physiology
Volume206
Issue number1
DOIs
Publication statusPublished - Jan 2006

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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    Russo, A., Corsale, S., Agnese, V., Macaluso, M., Cascio, S., Bruno, L., Surmacz, E., Dardanoni, G., Valerio, M. R., Vieni, S., Restivo, S., Fulfaro, F., Tomasino, R. M., Gebbia, N., & Bazan, V. (2006). TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma. Journal of Cellular Physiology, 206(1), 181-188. https://doi.org/10.1002/jcp.20447