A mutant TP53 gene status is associated with a poor prognosis and anthracycline-resistance in breast cancer patients.
This study evaluates the prognostic and predictive relevance of a mutated p53 in a series of 254 samples from primary breast cancer patients. C-erbB-2 analysis was defined in a limited subpopulation of 79 patients. p53 and c-erbB-2 status was analysed by immunohistochemical staining of the tumour samples. Positive p53 immunostaining was present in 86 cases (34%) and correlated with a high malignant grade, negative progesterone receptor status and ductal histology of tumour. C-erbB-2 positivity was seen in 38 samples (48%). Within an average follow-up time of 74 months, 121 patients developed recurrent or metastatic disease. Patients with mutated p53 showed a statistically significant shorter overall survival and disease-free survival in both univariate and multivariate analyses. The worst clinical outcome was seen in patients who were both p53- and c-erbB-2-positive. The response rate to anthracycline-based chemotherapy in metastatic disease was low in the p53-positive cases. Our results help to clarify the independent prognostic role of a mutated p53 status in breast cancer patients, indicating that this gene might be predictive of anthracycline resistance. Patients with a mutant p53 status and overexpressing c-erbB-2 should be regarded as high-risk cases.
Rahko
E
E
Department of Oncology, Oulu University Hospital, PL 22, FIN-90229 Oulu, Finland.
Blanco
G
G
Soini
Y
Y
Bloigu
R
R
Jukkola
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018734:Genes, erbB-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D016019:Survival Analysis
D000903:Antibiotics, Antineoplastic