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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 p53GeneChip 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.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Bosch FX,Ritter D,Enders C,Flechtenmacher C,Abel U,Dietz A,Hergenhahn M,Weidauer H

doi

10.1002/ijc.11698

keywords:

subject

Has Abstract

pub_date

2004-09-10 00:00:00

pages

530-8

issue

4

eissn

0020-7136

issn

1097-0215

journal_volume

111

pub_type

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