WT1 expression in vessels varies with histopathological grade in tumour-bearing and control tissue from patients with breast cancer

乳腺癌患者肿瘤组织和对照组织中 WT1 在血管中的表达随组织病理学等级的不同而变化

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作者:Richard J McGregor, You-Ying Chau, Timothy J Kendall, Mara Artibani, Nicholas Hastie, Patrick W F Hadoke

Background

The Wilms' tumour protein (WT1), which influences tumour development and angiogenesis, is a promising therapeutic target in breast cancer. We hypothesised that WT1 expression would vary in endothelial cells in distinct sub-classifications of breast cancer.

Conclusions

Expression of WT1 is increased in breast cancers but this is not limited to the vascular compartment. The association between reduced WT1 in tumour-free tissue and poor prognosis suggests a protective role for WT1 in the healthy breast.

Methods

WT1 expression and vascular density were quantified by immunohistochemical analysis of human (n = 57) and murine breast cancers. Human tumours were sub-classified by histopathological grade, ER status and HER2 enrichment.

Results

WT1 was identified in endothelial (and epithelial and smooth muscle) cells in tumours and tumour-free tissues (controls) from patients and mice with breast cancer. WT1 expression was higher in tumours than in controls, but this was not due to increased endothelial WT1. Vascular WT1 in cancers decreased as histopathological grade increased. WT1 was higher in ER-positive versus ER-negative cancers. Strikingly, reduced WT1 expression in controls correlated with an increased Nottingham Prognostic Index score. Conclusions: Expression of WT1 is increased in breast cancers but this is not limited to the vascular compartment. The association between reduced WT1 in tumour-free tissue and poor prognosis suggests a protective role for WT1 in the healthy breast.

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