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 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.

In frame deletion of intron-7 in the p53 gene in a human tonsil tumor.

We here report a unique intron deletion in the p53 gene. Analysis of a human tonsil tumor that expressed elevated levels of p53 showed a deletion of the entire intron 7 in one of the p53 alleles, leaving the coding sequence intact. The significance of the intron 7 deletion for the development of the tonsil tumor is discussed.

Nuclear-DNA content and p53 immunostaining in oral squamous-cell carcinoma - an analysis of a consecutive 10-year material.

In a retrospective analysis of 91 consecutive oral carcinomas we reviewed all patient records and weighed clinicopathological parameters against the results of image DNA cytometry and p53 immunhistochemical staining of the initial diagnostic biopsies. Eighty-seven percent of the biopsies were either aneuploid or nondiploid and there was a significant correlation between poorly differentiated tumours and aneuploidy. Sixty-nine percent of the tumours were p53 positive. DNA aberration or p53 positivity had no significant impact on prediction of survival or susceptibility to radiotherapy. In a multivariate analysis, T category had the greatest predictive value concerning survival. There was no correlation between p53 positivity and smoking.