METHODS: A total of 234 invasive cervical carcinomas (152 squamous cell carcinomas, 61 adenocarcinomas and 21 adenosquamous carcinomas) and 16 cervical intraepithelial neoplasia (CIN) I, six CIN II and 25 CIN III were immunohistochemically studied for p53.
RESULTS: p53 was detected more frequently in CIN and invasive carcinoma (100% of CIN I, 74.2% CIN II + III and 70.1% invasive carcinoma) compared with benign cervices (P< 0.001); however, only three squamous cell carcinomas, 11 adenocarcinomas and two adenosquamous carcinomas exhibited p53 expression in >75% of tumour nuclei. Six of the 11 adenocarcinomas and both adenosquamous carcinomas were poorly differentiated compared with one of the three squamous carcinomas. p53 immunoreactive cells were randomly distributed in invasive carcinoma, confined to the lower third of the epithelium in CIN I, reached the middle third in 20% of CIN II and upper third in 16.6% of CIN III.
CONCLUSIONS: Assuming that p53 immunoreactivity indicates gene mutation when the majority (> 75%) of neoplastic cells express p53, p53 mutations would seem uncommon in cervical carcinogenesis. Nonetheless, glandular malignancies, in particular poorly differentiated variants, may show a higher frequency of mutation. p53 was detected more frequently in CIN I compared with CIN II/III and invasive carcinoma which may be due to p53 protein degradation following interaction with high risk human papillomavirus E6 protein in CIN II/III and invasive carcinoma.
METHODS: Surgical samples from seven patients with a total of 17 sequential biopsies were retrieved for the study of p53 gene expression using immunohistochemical stain, and gene status by PCR-SSCP for exons 5-8. The tumours were graded according to the WHO classification criteria. P53 was distinctly over-expressed in five transformed higher grade biopsies, and all except one showed electrophoretic mobility shift in PCR-SSCP analysis. Sequencing analysis revealed single nucleotide substitutions in three of four of these high-grade transformed cases with band shift (75%), whereas some other studies reported a lower frequency of 25-30%, and mobility shift result was found to correlate with P53 expression. Lower grade tumours without P53 over-expression did not demonstrate band shift, and sequencing analysis did not reveal mutations.
CONCLUSIONS: We demonstrated the feasibility of adopting PCR-SSCP for screening of p53 mutations in archival tissue samples in this study, and there is a strong correlation of p53 gene over-expression and mutation events in high-grade transformed tumours.