LOSS OF WILD-TYPE P53 AND C-ERBB2 AMPLIFICATION CORRELATES WITH HIGH-GRADE BREAST CARCINOMAS

Breast cancer is the most common cancer in women in the western world. Two of the most frequently occuring chromosomal abnormalities in huma n breast carcinoma are the loss of p53 tumour suppressor gene function and the amplification of the c-erbB2 oncogene. Previous studies have demonstrated the role of p53 gene product in the maintenance of chromo somal stability and the correlation between c-erbB2 amplification and breast carcinogenesis. In this study we have examined the existence of a possible correlation between these genetic alterations in a panel o f 83 malignant breast tumours (69 adeno and 14 lobular carcinomas). Th e status of a related gene, c-erbB3, was also examined. With the aid o f microsattelite marker TP53CA loss of heterozygosity (LOH) was detect ed in the p53 locus in 49% of the tumours. Histochemical analysis of 6 4 of these tumours with the p53 antibody CM1 demonstrated staining, in dicative of an elevated steady-state level of p53 protein in 23 rumour s (36%). Amplification of the c-erbB2 gene was detected in 20 of 75 tu mours analysed (27%). In the tumours with c-erbB2 amplification 12 als o had p53 LOH. In at least another 2 tumours there was increased p53 p rotein level but no LOH. Therefore in 75% of the tumours with c-erbB2 amplification there was evidence of loss of normal p53 function. There was no evidence of c-erbB3 amplification in any of the 75 rumours ana lysed. The data presented demonstrates a strong correlation between th e loss of p53 and tumour grade (p<0.00545), and a strong association b etween c-erbB2, but not c-erbB3, amplification and loss of p53 (p<0.01 70).