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| PROGNOSTIC-SIGNIFICANCE OF P53 GENE ALTERATIONS IN NODE-NEGATIVE BREAST-CANCER |
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| Author(s): ELLEDGE RM, FUQUA SAW, CLARK GM, PUJOL P, ALLRED DC, MCGUIRE WL |
| Source: BREAST CANCER RESEARCH AND TREATMENT Volume: 26 Issue: 3 Pages: 225-235 Published: 1993 |
| Times Cited: 94 References: 37 |
| Abstract: 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 less-than-or-equal-to 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. Conclusion: 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.
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| Document Type: Article |
| Language: English |
| Reprint Address: ELLEDGE, RM (reprint author), UNIV TEXAS, HLTH SCI CTR, DIV MED ONCOL, 7703 FLOYD CURL DR, SAN ANTONIO, TX 78284 USA |
| Publisher: KLUWER ACADEMIC PUBL, SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS |
| Subject Category: Oncology |
| IDS Number: MB092 |
| ISSN: 0167-6806 |
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