Year: 1998
Type: article
Study design: Observational Study
Abstract: : p53 protein overexpression and/or gene mutations have been detected in ≥50% of breast cancers and are among the most frequent changes identified in human malignancies. We examined p53 protein immunoreactivity in random periareolar breast fine needle aspirates (FNA) from 270 women at high risk for breast cancer as well as 10 in situ and invasive lesions that later developed in this cohort. We correlated p53 immunopositivity with mutational analysis performed on microdissected tumor cells. The p53 antibody PAb240 was used on acetone-fixed cytospins. Nuclear staining for p53 was detected in 29% of high-risk women. The prevalence of p53 immunoreactivity was directly correlated with cytologic abnormality and was predictive of concurrent atypical hyperplasia in a multivariate analysis (p = 0.002). Four invasive cancers, three ductal carcinoma in situ (DCIS), and three lobular carcinoma in situ (LCIS) were subsequently detected at a median follow-up time of 33 months after the initial aspiration. p53 immunopositivity was predictive of later development of DCIS and/or invasive cancer in a univariate analysis (p = 0.0026). Five of the seven women who later developed DCIS or an invasive lesion were p53 immunopositive using PAb240. One of the two remaining women had insufficient cells for p53 analysis. To examine the correlation between p53 immunoreactivity in the initial aspirate, as detected by PAb240, and the presence of p53 mutation in the 10 surgical specimens of the lesions subsequently detected, we microdissected tumor cells from paraffin sections followed by PCR-SSCP analysis for p53 exons 5–9. Immunopositivity by PAb1801 and DO-1 antibodies and a mutation in the p53 gene were detected in only one of those lesions. Microdissection studies are under way to examine FNA immunopositive cytospins for the presence of p53 mutations by PCR-SSCP analysis. At the present time we conclude that conformational changes in the p53 molecule, in the presence or absence of corresponding p53 gene mutations, may play an important role in breast carcinogenesis.
Source: The Breast Journal
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1976154740