Expression of tumour markers and determination of microvessel density in MNU-induced breast tumour
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Date
2009
Authors
Mohd Nafi, Siti Norasikin
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Abstract
Angiogenesis plays an important role in breast tumour development. The association
of this phenomenon with the expression of breast tumour markers has not been fully
elucidated. In this study, breast tumours were induced by injecting rats intraperitoneally
with 1-methyl-1-nitrosurea (MNU) at dose of 70 mg/kg body weight in 3 consecutive
days into 21-days old rats. The breast tumours were then subjected to intratumoural
angiogenesis promotion using basic Fibroblast Growth Factor (bFGF) or inhibition
using Platelet Factor 4 (PF4) at dose 10μg/tumour. The size of the tumours was
monitored. The tumour tissues taken were subjected to quantitative-RTPCR for ER, PR,
EGFR, cerbB2, E-cadherin and LR expression. Angiogenesis was determined by
microvessel density with immunohistochemical staining for FVIII-RA. Histological
findings showed most of the MNU-induced breast tumours were malignant where
cribriform type predominated papillary type. Benign and preneoplastic lesions were
seen mainly in tumours of size less than 1.2 cm. Promoting angiogenesis appear to have
similar histological features with the control group. We noted that suppression of
angiogenesis appeared to increase tumour necrosis and the number of diffuse infiltrating
ductal carcinoma, not specified type (NST). It was clearly seen that tumour growth in
control group shows dependency on peritumoural and intratumoural blood vessels.
There was significant increase in the number of intratumoural blood vessels compared
to peritumoural blood vessels. PF4-treated breast tumours have significant reduction of
tumour blood vessels and bFGF-treated breast tumours do not show any significant
increase of tumour blood vessel. As tumour grew, there was significant increase of ER,
PR, EGFR and cerbB2 expressions. The expressions of EGFR and cerbB2 continue to
increase irrespective of whether angiogenesis is increased or suppressed. We also noted
that the invasiveness of breast tumours was increased in PF4-treated group by decrease
expressions of ER and PR; and increase expression of LR. We found a significant
association between increased MVD and overexpressions of ER, PR, EGFR, c-erbB2
and LR mRNA, and downregulation of E-cadherin mRNA expression in the control
group. This association occurs irrespective whether the MVD is in peritumoural or
intratumoural regions. There was also significant association between peritumoural
MVD with the expressions of ER, PR and LR seen in bFGF-treated group. There was
significant association between intratumoural MVD with the expressions of ER and PR
seen in PF4-treated group. In conclusion, our findings have shown that reduction of
blood supply to breast tumour causes increase aggressiveness of the tumour as
illustrated by the presence of more aggressive phenotypes in the PF4-treated group with
down regulations of ER and PR in the intratumoural region. Eventhough tumour
phenotype in the angiogenic promoted group was similar to the control group, the
growth rate was faster and this was supported by significant association with increased
expressions of ER, PR and LR in the peritumoural region. We also noted that
expressions of EGFR and cerbB2 in promoting tumour growth and down regulation of
E-cadherin were independent of angiogenesis.
Description
Master
Keywords
Medical science , Tumour markers , Microvessel , Breast tumour