Prognostic significance of p53 gene alterations in node-negative breast cancer.
Mutations in the p53 gene can play a role in the transformation of normal to malignant cells. Because these mutations are more frequently reported later in the course of transformation, their presence could reflect a greater malignant potential of the tumor and, thus, an increased probability of metastasis and recurrence after local therapy. In a pilot study using single-stranded conformation polymorphism analysis (SSCP), 200 node-negative breast tumors were examined for mutations in the region encompassing exons 5 through 9 of the p53 gene. Exons 5 through 9 were tested because they contain 80-90% of known p53 gene mutations. The tumors ranged in size from 1 to 3 cm. 28 tumors were found to have an abnormal band pattern on both initial and repeat analysis. 4 of these tumors were sequenced; 3 contained a p53 mutation and the 4th had a rare neutral polymorphism. Disease-free survival (DFS) at 5 years for women with tumors having an abnormal SSCP analysis was 57% (+/- 10%), compared to a 79% (+/- 3%) DFS for the group with a normal pattern. By the log rank test, this difference was highly significant, p < or = 0.01. The relative risk of recurrence for the group with an abnormal SSCP pattern was 2.2. In a multivariate analysis including ER, PgR, ploidy, S-phase, age, and tumor size, an abnormal p53 by SSCP analysis and patient age were the only factors that independently predicted DFS at 5 years.


CONCLUSIONS
Women with node-negative breast cancer who have tumors with alterations in the p53 gene, as indicated by SSCP analysis, have a significantly poorer prognosis and a higher rate of relapse at 5 years. The prognostic significance is maintained in a multivariate analysis including many established prognostic factors.
Elledge
R M
RM
University of Texas Health Science Center, Division of Medical Oncology, San Antonio 78284-7884.
Fuqua
S A
SA
Clark
G M
GM
Pujol
P
P
Allred
D C
DC
McGuire
W L
WL
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004277:DNA, Single-Stranded / Q000032:analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009690:Nucleic Acid Conformation; D011110:Polymorphism, Genetic; D011379:Prognosis
D003062:Codon; D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded