Head and neck tumor sites differ in prevalence and spectrum of p53 alterations but these have limited prognostic value

Abstract

The tumor site is a strong clinical factor in head and neck squamous cell carcinoma (HNSCC). To clarify the biologic and clinical role of p53 alterations in HNSCC, we have examined the prevalence and the nature of p53 alterations in a large cohort of tumors from the different sites. For immunohistochemical analysis of p53 protein expression, we introduced tyramide signal amplification immunohistochemistry (TSA-IHC) on a tissue microarray. This allowed the discrimination between normal low-level expression and reduced or lost expression. Two hundred fifty-three tumors were subjected to mutational analysis by genomic DNA sequencing, employing also the p53 GeneChip from Affymetrix. The prevalence of all p53 alterations, i.e., mutations, overexpression and loss of expression, was significantly higher in hypopharyngeal tumors than in the other sites (p ‫؍‬ 0.001). Laryngeal tumors showed the lowest rate of p53 alterations, but revealed a distinct mutation spectrum: most mutations affected exon 5 (p ‫؍‬ 0.013) and the S2 domain (p ‫؍‬ 0.002), and most hot-spot 248 mutations occurred in the larynx (p < 0.001). Sequencing by p53 GeneChip technology was shown to be only insignificantly more sensitive than dideoxy sequencing. In agreement with p53 mutations occurring prior to invasiveness, their prevalence did not increase with tumor stage, and all mutation classes lacked prognostic significance. The large patient cohort of this study showed that p53 is differentially affected in the different tumor sites of the head and neck, but its mode of inactivation does not play a major role in tumor progression.

Valor prognóstico da correlação imunoistoquímica do Ki-67 e p53 em carcinomas epidermóides da laringe

“…This is probably due to the fact that the authors did not choose only tumors in the larynx, but in the whole head and neck region. Bosch et al 16 reported that the prevalence of p53 alterations (mutation, expression, and expression loss) is significantly higher in hypopharyngeal tumors than in other sites.…”

P53 expression in squamous cell carcinomas of the supraglottic larynx and its lymph node metastases

“…In most studies, the inactivation of the p53 gene has been investigated by determining the levels of p53 protein using immunohistochemistry on the basis that the half-life of the wild-type protein is too short to permit detection, whereas the mutant protein is stable. 3 In HNSCC, several studies have reported that overexpression of p53 correlates with clinicopathologic characteristics of the tumor, such as lymph node metastases, and disease survival. 4 However, a number of other studies failed to demonstrate a correlation between p53 expression and these clinicopathologic variables.…”

“…4 However, a number of other studies failed to demonstrate a correlation between p53 expression and these clinicopathologic variables. 3,5 The degree of heterogeneity in HNSCC in terms of the population of patients, disease site, stage, treatment, and supportive care limits the suitability of HNSCC for analysis. Most studies that have evaluated the prognostic significance of p53 have been performed in sets of patients with HNSCC from different sites (oral cavity, pharynx, and larynx).…”

p53 mutation, but not in vitro predictor genes of therapeutic efficacy of cisplatin, is clinically relevant in comparing partial and complete responder cases of maxillary squamous cell carcinoma

“…A number of previous studies on the prevalence of p53 alterations in patients with head and neck squamous cell carcinoma described a range of 44-68% of cases with the disease (15-18). Bosch et al showed that the prevalence of p53 alterations varies in different sites of head and neck squamous cell carcinoma, where it is significantly higher in hypopharyngeal tumors (66%), than in the other sites (38%) (19). However, few reports have addressed the prevalence of p53 mutations in maxillary squamous cell carcinoma.…”