Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value.
Human cancer cells with a mutated p53 tumor-suppressor gene have a selective growth advantage and may exhibit resistance to ionizing radiation and certain chemotherapeutic agents. To examine the prognostic value of mutations in the p53 gene, a cohort of 90 Midwestern Caucasian breast cancer patients were analyzed with methodology that detects virtually 100% of all mutations. The presence of a p53 gene mutation was by far the single most predictive indicator for recurrence and death (relative risks of 4.7 and 23.2, respectively). Direct detection of p53 mutations had substantially greater prognostic value than immunohistochemical detection of p53 overexpression. Analysis of p53 gene mutations may permit identification of a subset of breast cancer patients who, despite lack of conventional indicators of poor prognosis, are at high risk of early recurrence and death.
Kovach
J S
JS
Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Hartmann
A
A
Blaszyk
H
H
Cunningham
J
J
Schaid
D
D
Sommer
S S
SS
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D017931:DNA Primers; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008969:Molecular Sequence Data; D009154:Mutation; D009367:Neoplasm Staging; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012008:Recurrence; D012307:Risk Factors; D012680:Sensitivity and Specificity; D017384:Sequence Deletion; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D017931:DNA Primers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53