Correspondence

Clinical Response to Fluorouracil and p53

N Engl J Med 2001; 345:1065-1066October 4, 2001

Article

To the Editor:

A prior report from an Eastern Cooperative Oncology Group trial of adjuvant therapy (EST 2284), one of the trials that provided samples for the study by Watanabe et al. (April 19 issue),1 showed that there is a statistically significant association between low-level amplification of the c-myc gene and improved responses to fluorouracil.2 Subsequently, it was also shown that both wild-type p53 and very high levels of c-myc are required for the induction of apoptosis of colon-cancer cells by fluorouracil in vitro.3 Moreover, only patients whose tumors had amplified c-myc and wild-type p53 had good outcomes with adjuvant therapy.

Investigation of p53 mutations by single-strand conformation polymorphism analysis and sequence analysis has revealed a significant association between the presence of a mutation and poorer outcome in patients in trial EST 2284 (unpublished data), in contrast to the lack of correlation between p53 protein levels and survival reported by Watanabe et al.1 These data support previous reports that the level of p53 protein is not an accurate surrogate marker of p53 mutations.

Leonard H. Augenlicht, Ph.D.
Scott Wadler, M.D.
Diego Arango, Ph.D.
Albert Einstein Cancer Center, Bronx, NY 10467
augen@aecom.yu.edu

3 References

1. 1

   Watanabe T, Wu T-T, Catalano PJ, et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med 2001;344:1196-1206
   Full Text | Web of Science | Medline

2. 2

   Augenlicht LH, Wadler S, Corner G, et al. Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: a frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial. Cancer Res 1997;57:1769-1775
   Web of Science | Medline

3. 3

   Arango D, Corner GA, Wadler S, Catalano PJ, Augenlicht LH. c-myc/p53 Interaction determines sensitivity of human colon carcinoma cells to 5-fluorouracil in vitro and in vivo. Cancer Res 2001;61:4910-4915
   Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Minetta C Liu, Edward P Gelmann. (2002) P53 gene mutations: Case study of a clinical marker for solid tumors. Seminars in Oncology 29:3, 246-257
   CrossRef