Mutations in p53, p53 protein overexpression and breast cancer survival.
p53 is an important tumour suppressor gene that encodes p53 protein, a molecule involved in cell cycle regulation and has been inconsistently linked to breast cancer survival. Using archived tumour tissue from a population-based sample of 859 women diagnosed with breast cancer between 1996 and 1997, we determined p53 mutations in exons 5-8 and p53 protein overexpression. We examined the association of p53 mutations with overexpression and selected tumour clinical parameters. We assessed whether either p53 marker was associated with survival through 2002, adjusting for other tumour markers and prognostic factors. The prevalence of protein overexpression in the tumour was 36% (307/859) and of any p53 mutation was 15% (128/859). p53 overexpression was positively associated with the presence of any p53 mutation (odds ratio [OR]= 2.2, 95% confidence interval [CI]= 1.5-3.2), particularly missense mutations (ER = 7.0, 95% CI = 3.6-13.7). Negative oestrogen and progesterone receptor (ER/PR) status was positively associated with both p53 protein overexpression (= 2.6, 95% CI = 1.7-4.0) and p53 mutation (OR = 3.9, 95% CI = 2.4-6.5). Any p53 mutation and missense mutations, but not p53 protein overexpression, were associated with breast cancer-specific mortality (hazard ratio [HR]= 1.7, 95% CI = 1.0-2.8; HR = 2.0, 95% CI = 1.1-3.6, respectively) and all-cause mortality (HR = 1.5, 95% CI = 1.0-2.4; HR = 2.0, 95% CI = 1.2-3.4, respectively); nonsense mutations were associated only with breast cancer-specific mortality (HR = 3.0, 95% CI = 1.1-8.1). These associations however did not remain after adjusting for ER/PR status. Thus, in this population-based cohort of women with breast cancer, although p53 protein overexpression and p53 mutations were associated with each other, neither independently impacted breast cancer-specific or all-causing mortality, after considering ER/PR status.
Rossner
Pavel
P
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA. prossner@biomed.cas.cz
Gammon
Marilie D
MD
Zhang
Yu-Jing
YJ
Terry
Mary Beth
MB
Hibshoosh
Hanina
H
Memeo
Lorenzo
L
Mansukhani
Mahesh
M
Long
Chang-Min
CM
Garbowski
Gail
G
Agrawal
Meenakshi
M
Kalra
Tara S
TS
Gaudet
Mia M
MM
Teitelbaum
Susan L
SL
Neugut
Alfred I
AI
Santella
Regina M
RM
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53