An important role for BRCA1 in breast cancer progression is indicated by its loss in a large proportion of non-familial breast cancers.
The presence of BRCA1 protein was determined immunohistochemically in normal and benign breast biopsies, non-familial 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 < 0.001) and non-familial breast cancer (p = 0.001). In non-familial 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.
CRC Laboratories, Department of Medical Oncology, Charing Cross Hospital, Imperial College of Medicine, London, UK.
J
J
Taylor
M
M
Lymboura
P E
PE
Pace
R P
RP
A'hern
A J
AJ
Desai
S
S
Shousha
R C
RC
Coombes
S
S
Ali
D000328:Adult; D000818:Animals; D019313:BRCA1 Protein / Q000276:immunology / Q000378:metabolism*; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D018450:Disease Progression; D006367:HeLa Cells; D006801:Humans; D007106:Immune Sera; D007150:Immunohistochemistry; D014162:Transfection
D019313:BRCA1 Protein; D007106:Immune Sera