M. Tavassoli et al., LOSS OF WILD-TYPE P53 AND C-ERBB2 AMPLIFICATION CORRELATES WITH HIGH-GRADE BREAST CARCINOMAS, International journal of oncology, 6(1), 1995, pp. 181-186
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).