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.
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Master
Keywords
Medical science , Tumour markers , Microvessel , Breast tumour
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