Genetic alterations in early-onset invasive breast carcinomas: Correlationof c-erbB-2 amplification detected by fluorescence in situ hybridization with p53 accumulation and tumor phenotype
M. Fiche et al., Genetic alterations in early-onset invasive breast carcinomas: Correlationof c-erbB-2 amplification detected by fluorescence in situ hybridization with p53 accumulation and tumor phenotype, INT J CANC, 84(5), 1999, pp. 511-515
p53 tumor-suppressor gene mutation and p53 protein over-expression have bee
n reported with higher frequency in early-onset breast carcinomas (EOBC). G
iven the role attributed to normal p53 protein in DNA-repair mechanisms, ot
her somatic genomic alterations would be expected to be associated with thi
s abnormality. Amplification of the c-erbB-2 (HER-2/neu) oncogene and over-
expression of the corresponding p185erbB-2 protein have been linked to prog
nosis and response to therapy in breast cancer. In a retrospective study of
62 formalin-fixed paraffin-embedded invasive EOBC (diagnosed at 35 years o
r less), the amplification status of the c-erbB-1 gene detected by fluoresc
ence in situ hybridization (FISH) using a unique sequence probe was compare
d with p53 protein accumulation measured by immunohistochemistry (IHC) and
phenotypic features. p185erbB2-protein expression was also detected by immu
nohistochemistry, together with estrogen-receptor (ER) and progesterone-rec
eptor (PR) expression. The data for a sub-set of 33 node-negative EOBC case
s were compared with 70 node-negative tumors diagnosed in women above 36 ye
ars of age. Compared with node-negative BC in older women, node-negative EO
BC was significantly move likely to feature high grade, high proliferation
rate, negative ER and/or PR and p53 over-expression ( p < 0.05). A trend to
ward a higher incidence of c-erbB-2 amplification in EOBC (21% vs. 9%) reac
hed near-significance (p = 0.07). In EOBC, c-erbB-2 amplification and p53 o
ver-expression were not associated with high tumor grade or high cell-proli
feration rate, in contrast to the significant associations of these markers
in tumors in older women. Abnormalities in tumor markers, including c-erbB
-2 gene amplification and p53-protein over-expression, occur at different r
ates in women with EOBC as compared with BC developing in older women. This
finding may reflect a different pathogenesis for EOBC, and warrants furthe
r investigation. Int. J. Cancer (Pred. Oncol.) 84:511-515, 1999. (C) 1999 W
iley-Liss, Inc.