TP53 MUTATIONS AND BREAST-CANCER PROGNOSIS - PARTICULARLY POOR SURVIVAL RATES FOR CASES WITH MUTATIONS IN THE ZINC-BINDING DOMAINS

Acquired mutations in TP53 as well as immunohistochemically detectable protein expression have been implicated as prognostic factors for bre ast cancer. We have evaluated the relationship between mutations detec ted in 119 breast tumours and various clinicohistopathological indices , stratifying the mutations according to the functional domains as def ined by the recent elucidation of the crystal structure of the protein . Patients with missense mutations located in regions encoding parts o f the protein involved in zinc-binding had significantly decreased dis ease-free and overall survival relative to patients whose tumours had mutations in other domains. These results indicate that these biochemi cally defined domains also have biological relevance in terms of breas t cancer disease course, and suggest that some mutations in TP53, more than others, can contribute to the development of clinically more agg ressive and perhaps treatment resistant breast tumours. When confirmed , this will be of potential importance in predicting the clinical beha viour of breast cancer and its responsiveness to therapy. (C) 1995 Wil ey-Liss, Inc.