P53 MUTATIONS AND C-ERBB-2 AMPLIFICATION IN INTRADUCTAL AND INVASIVE BREAST CARCINOMAS OF HIGH HISTOLOGIC GRADE

In order to clarify the clinical significance of mutations of the p53 gene and amplification of the c-erbB-2 gene in breast carcinoma, these gene alterations were examined in 101 invasive, seven predominantly intraductal and 10 intraductal breast carcinomas by single-strand conformation polymorphism-direct sequencing or Southern blot-hybridization analysis. p53 mutations were detected in 32 (32%) of the invasive cases and two (12%) of the 17 intraductal/predominantly intraductal cases, whereas c-erbB-2 amplification was detected in 14 (14%) of the invasive and six (35%) of the intraductal/predominantly intraductal cases. Irrespective of differences in the positions and types of the mutations, cases carrying p53 mutations were almost always Grade 3 histologically and with a low hormone-receptor value. Since p53 mutations as well as c-erbB-2 amplification were detected almost selectively in Grade 3 cases but were not associated with lymph nodal status in invasive breast cancer, these two gene alterations could be indicators of prognosis of disease independent of lymph nodal status. Even in intraductal/predominantly intraductal carcinoma, these gene alterations were almost always detected in tumors of higher histologic grade. Thus, it is suggested that these gene alterations occur in breast cancers showing a high proliferation rate irrespective of the presence of invasion, and that other molecular alterations are involved in the process of breast cancer invasion.