p53 protein expression and gene mutation in phyllodes tumors of the breast

The malignant potential of mammary phyllodes tumors is difficult to assess on initial pathologic examination. Studies on the p53 tumor suppressor gene have shown that it has an important role in the development of a variety o f malignancies, yet the specific contribution to the pathogenesis and devel opment of the malignant potential of phyllodes tumor is largely unknown. We studied p53 protein expression in 25 cases of phyllodes tumors histologica lly classified as either malignant (12 cases) or benign (13 cases). Using m icrodissection approach, we also analyzed the p53 gene sequence in a case t hat demonstrated progression from benign to malignant phenotype. Nuclear p53 staining was detected in various proportions (1-90%) of neoplas tic stromal cells of malignant tumors. No staining was found in benign tumo rs. Progression from benign to malignant phenotype was associated with a si gnificant increase in the accumulation of p53 (more than 20 times). This wa s caused by an underlying missense mutation in exon 7, resulting in a chang e from Arg(248) to Trp(248) in the malignant component of the tumor. Stromal p53 over-expression was observed only in neoplasms histologically c lassified as malignant and was associated with an increased proliferation i ndex (MIB-1 staining). These two markers may be used as useful adjuncts in the diagnosis of malignancy in difficult cases or when only a limited sampl e size is available. Somatic mutation in exon 7 of p53 gene in malignant ph yllodes tumor points toward the importance of p53 in the malignant transfor mation of phyllodes tumors.