Refined characterization of head and neck squamous cell carcinomas expressing a seemingly wild-type p53 protein

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Abstract
A fraction of head and neck squamous cell carcinomas (HNSCC) reveal overexpression of the p53 protein although sequence analysis failed to detect mutations in the core region of the protein. The functional and clinical status of p53 in these tumors is unclear.In 31 HNSCC, allelic imbalances (AI) at TP53 and other chromosome 17 loci were analyzed by microsatellite marker analysis. Expression of p16(INK4a) protein was analyzed by immunohistochemistry. Seven tumors were re-examined for sequence alterations by the Affymetrix p53 GeneChip.About 54.8% of these tumors showed AI at TP53; 41.9% showed loss of p16, an overlapping fraction of 35.5% demonstrated AI and p16 loss. Six of seven such tumors revealed heterozygous missense mutations.A large proportion of HNSCC with presumed wild-type p53 overexpression are false-negative cases. These results strengthen the established strong association of p53 protein overexpression with missense mutations. AI at TP53 and p16 loss are useful surrogate markers for genetic alterations of TP53 in HNSCC.