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 sel ective growth advantage and may exhibit resistance to ionizing radiati on and certain chemotherapeutic agents, To examine the prognostic valu e of mutations in the p53 gene, a cohort of 90 Midwestern Caucasian br east cancer patients were analyzed with methodology that detects virtu ally 100% of all mutations, The presence of a p53 gene mutation was by far the single most predictive indicator for recurrence and death (re lative risks of 4.7 and 23.2, respectively), Direct detection of p53 m utations had substantially greater prognostic value than immunohistoch emical 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.