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.

Prognostic significance of ploidy and S-phase fraction in primary intraoral squamous cell carcinoma and their corresponding metastatic lymph nodes

“…Russo et al [31] revealed that among 36 patients with locally advanced squamous cell carcinoma, the major significant predictor of both disease relapse and death was high SPF and TP53 mutation. Hass et al [32] performed flow cytometric analysis of 48 primary and recurrent head and neck squamous cell carcinoma tumors.…”

Specific TP53 mutations predict aggressive phenotype in head and neck squamous cell carcinoma: a retrospective archival study

“…Similarly, some researchers have failed to find such a correlation [38,39]. On the other hand, positive association between the TP53 mutations and poor prognosis have been published [36,40,41]. Patients with TP53 mutations have been shown to have a significantly shorter survival time than those without any TP53 mutations [42].…”

“…We show here that TP53 mutations in exons 6 and 8 correlate with poorer overall survival. Russo and co-workers (2006) have noticed that TP53 mutations within exons 5 and 8 are strong prognostic indicators of both disease recurrence and survival in patients with locally advanced laryngeal squamous cell carcinoma [41]. Similarly, Huang and co-workers (1998) have studied 204 cases of non-small cell lung carcinoma, and patients with mutations in exons 7 and 8 have a significantly shorter survival compared with patients with other mutations or no mutation [44].…”

The pattern of p53 gene mutations on oral squamous cell carcinoma

“…The incidence of p53 mutation over 50% was frequently found in exon 5-8 in all cancers especially exon 5 and 7 for colorectal and laryngeal carcinoma. 7,8 In this study the incidence of p53 mutation in OSCC has shown 28/40 (70%), exon 7; 22/40 (55%) and exon 5; 11/40 (27.5%). The result indicated that mutation of gene p53 more frequently involved in molecular control of OSCC cell cycle and it is not influenced by alteration of other tumor suppressor gene inactivation in OSCC cell cycle.…”