title: p53 overexpression in normal and dysplastic tissues adjacent to p53 negative squamous cell carcinomas of the head and neck.
abstract: p53 overexpression was present in the normal or dysplastic epithelium, but absent in the adjacent invasive cancers of five patients with head 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 conformation polymorphism (SSCP) results from exon 7 and 8 were also obtained. Bandshifts 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 dysplasia 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 substitution in the protein sequence. In the adjacent IHC p53 negative invasive cancer lesions, no bandshifts could be observed by SSCP, and sequencing did not reveal any mutated p53. WAF1/p21 (IHC) expression was assayed to study p53 function. Image cytometry (ICM) DNA analysis, estimating 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, moderate, and severe dysplasia indicates that p53 mutation, not only p53 immunoreactivity, can be an early event in HNSCC carcinogenesis. The lack of p53 immunoreactivity in the invasive cancers adjacent to p53 positive dysplasias could possibly be attributed to loss of the mutant allele, or clonal heterogeneity.
authors.affiliation: KAROLINSKA HOSP,KAROLINSKA INST,DEPT TUMOR PATHOL,S-17177 STOCKHOLM,SWEDEN. HUDDINGE UNIV HOSP,KAROLINSKA INST,DIV CLIN VIROL,S-14186 HUDDINGE,SWEDEN. KAROLINSKA HOSP,KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. DANDERYD HOSP,DEPT PATHOL,S-18288 DANDERYD,SWEDEN.
authors.forename: E
authors.initials: E
authors.lastname: Munckwikland
authors.forename: H
authors.initials: H
authors.lastname: Blegen
authors.forename: I
authors.initials: I
authors.lastname: Lewensohnfuchs
authors.forename: M
authors.initials: M
authors.lastname: Malec
authors.forename: G
authors.initials: G
authors.lastname: Auer
authors.forename: R
authors.initials: R
authors.lastname: Kuylenstierna
authors.forename: T
authors.initials: T
authors.lastname: Dalianis
authors.forename: K
authors.initials: K
authors.lastname: Wiman
authors.forename: J
authors.initials: J
authors.lastname: Lindholm