An important role for BRCA1 in breast cancer progression is indicated by its loss in a large proportion of non-familial breast cancers
✍ Scribed by Jacqueline Taylor; Margarita Lymboura; Paul E. Pace; Roger P. A'hern; Anil J. Desai; Sami Shousha; R. Charles Coombes; Simak Ali
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 625 KB
- Volume
- 79
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The presence of BRCA1 protein was determined immunohistochemically in normal and benign breast biopsies, nonfamilial breast carcinomas and breast carcinomas from one or more individuals from 8 BRCA1 families. Strikingly, little staining was detected in breast carcinomas from BRCA1 families, regardless of the position or type of mutation, whereas strong immunostaining was observed in 28/28 of non-malignant breast biopsies. Furthermore, BRCA1 staining was reduced in non-familial breast carcinomas, since loss of nuclear BRCA1 staining was evident in 19% of non-familial breast carcinomas whilst a similar proportion (20%) showed absence of either cytoplasmic or nuclear BRCA1 staining. Statistical analysis indicates that breast cancer is characterised by a reduction in levels of nuclear BRCA1 in familial (p F 0.001) and non-familial breast cancer (p ؍ 0.001). In nonfamilial breast cancer absence of nuclear BRCA1, but not cytoplasmic BRCA1, is more common in high grade breast carcinomas (p ؍ 0.03) and in patients with evidence of lymph node involvement (p ؍ 0.05). Correlation between the absence of BRCA1 protein with high grade is consistent with previous findings of a correlation between mutations in the BRCA1 gene and high grade. Our findings provide new evidence in support of BRCA1 as a tumour suppressor protein in non-familial breast cancer.