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Mutations in exons 5–8 of the p53 gene, independent of their type and location, are associated with increased apoptosis and mitosis in invasive breast carcinoma
Author(s) -
van Slooten HenkJan,
van de Vijver Marc J.,
Børresen AnneLise,
Eyfjörd Jorunn E.,
Valgardsdóttir Rut,
Scherneck Siegfried,
Nesland Jahn M.,
Devilee Peter,
Cornelisse Cees J.,
van Dierendonck Jan Hein
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199912)189:4<504::aid-path483>3.0.co;2-a
Subject(s) - exon , biology , cancer research , mutation , apoptosis , mitosis , gene , breast cancer , mutant , gene mutation , microbiology and biotechnology , cancer , genetics
In breast cancer, mutations located in the zinc‐binding functional domains of the p53 gene have been reported to predict a worse prognosis and a worse response to treatment with doxorubicin, compared with mutations in other parts within exons 5–8 of the gene. Similarly, mutations in residues of p53 that directly contact DNA have been associated with a poor prognosis. To investigate whether these specific p53 mutations are associated with differences in the rate of apoptosis and/or mitosis, or expression of the anti‐apoptotic Bcl‐2 protein, these parameters were evaluated in 89 invasive breast cancers with a confirmed p53 mutation in exons 5–8 and in 99 tumours without a p53 mutation in exons 5–8. Neither mutations located in the zinc‐binding functional domains nor mutations in residues that directly contact DNA were associated with alterations in mitotic or apoptotic activity. However, compared with the wild‐type p53 tumours, both apoptotic and mitotic indices showed an approximately two‐fold increase in the mutant p53 group ( p < 0·001). The presence of a p53 mutation was also associated with the presence of tumour necrosis ( p < 0·001), high tumour grade ( p < 0·001) and low expression of Bcl‐2 ( p < 0·001). Our data support the concept that in invasive breast carcinoma, loss of p53 function is involved in enhanced proliferation rather than decreased apoptosis and that the resulting acceleration of cell turnover may enhance clonal evolution and tumour progression. Copyright © 1999 John Wiley & Sons, Ltd.