p53 and survival in early onset breast cancer : Analysis of gene mutations, loss of heterozygosity and protein accumulation

• Published in: European journal of cancer (1990) Vol. 35; no. 8; pp. 1202 - 1207
• Main Authors: GENTILE, M, JUNGESTRÖM, M. B, OLSEN, K. E, SÖDERKVIST, P, WINGREN, S
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01-08-1999
• Subjects: Adult; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Female; Genes, p53 - genetics; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Loss of Heterozygosity; Mammary gland diseases; Medical sciences; MEDICIN; MEDICINE; Mutation - genetics; Neoplasm Proteins - metabolism; Polymerase Chain Reaction - methods; Prognosis; Survival Analysis; Tumor Suppressor Protein p53 - metabolism; Tumors; Human; Immunohistochemistry; Carcinoma; Prognosis; p53 Protein; Malignant tumor; Survival; Accumulation; Polymerase chain reaction; Pathology; Mammary gland diseases; TP53 Gene; Age of onset; Young adult; Loss of heterozygosity; Early; Mammary gland; Mutation; Molecular biology; Tumor suppressor gene
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/s0959-8049(99)00121-5

The p53 protein has proven to be central in tumorigenesis by its cell cycle regulatory properties and both gene mutations and protein accumulation have been associated with poor prognosis in breast cancer. The present study was undertaken to investigate the prognostic significance of gene mutations, p53 protein accumulation and of loss of heterozygosity (LOH) at the TP53 locus in young (age < 37 years) breast cancer patients. In total, gene mutations were found in 21 of the 123 patients (17%), LOH in 20 of the 47 informative cases (43%) and protein accumulation in 47 of the 102 available cases (46%). Log rank analysis revealed no significant association between survival and TP53 mutations (in general), p53 protein accumulation or LOH. However, missense mutations localised to the zinc binding domain were significantly (P = 0.0007) associated with poorer prognosis. As indicated in this as well as other studies, p53 protein accumulation is frequently found in young breast cancer patients, but this protein overexpression appears to be of minor significance for survival. Nevertheless, the present report also suggests that specific mutations contribute substantially to tumour aggressiveness.