P53 OVEREXPRESSION IN NORMAL AND DYSPLASTIC TISSUES ADJACENT TO P53 NEGATIVE SQUAMOUS-CELL CARCINOMAS OF THE HEAD AND NECK

p53 overexpression was present in the normal or dysplastic epithelium, but absent in the adjacent invasive cancers of five patients with hea d and neck squamous cell carcinomas (HNSCC), when p53 immunostaining ( IHC) was performed. In three of the five p53 immunoreactive dysplasias and adjacent p53 negative invasive cancers single stranded conformati on polymorphism (SSCP) results from exon 7 and 8 were also obtained. B andshifts in exon 7 were detected in two dysplasias, and bandshifts in exon 8 were found in a third. Sequencing of exon 7 in the first dyspl asia with bandshift indicated a deletion of codon 241-242 (loss of CT) resulting in a frame shift. In the second dysplasia with bandshift a mutation was observed in codon 244 resulting in a Gly-->Arg substituti on in the protein sequence. In the adjacent IHC p53 negative invasive cancer lesions, no bandshifts could be observed by SSCP, and sequencin g did not reveal any mutated p53. WAF1/p21 (IHC) expression was assaye d to study p53 function. Image cytometry (ICM) DNA analysis, estimatin g genetic instability, showed progress in DNA aberration for invasive cancer lesions as compared with the dysplasias. Human papillomavirus ( HPV DNA) was not detected by a polymerase chain reaction (PCR) in any of the five cancers thus excluding possible p53 degradation caused by HPV protein. In conclusion, the finding of p53 mutations in mild, mode rate, and severe dysplasia indicates that p53 mutation, not only p53 i mmunoreactivity, can be an early event in HNSCC carcinogenesis. The la ck of p53 immunoreactivity in the invasive cancers adjacent to p53 pos itive dysplasias could possibly be attributed to loss of the mutant al lele, or clonal heterogeneity.