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Indian Journal of Cancer
Medknow Publications on behalf of Indian Cancer Society
ISSN: 0019-509X
EISSN: 1998-4774
Vol. 46, No. 4, 2009, pp. 303-310
Bioline Code: cn09072
Full paper language: English
Document type: Research Article
Document available free of charge

Indian Journal of Cancer, Vol. 46, No. 4, 2009, pp. 303-310

 en High frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in advanced breast tumors associated with aggressiveness of the tumor
Gupta, S; Joshi, K; Wig, J D & Arora, S K

Abstract

Background: The product of Wilms′ tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis and are known to facilitate angiogenesis. In the present study, WT1 allelic integrity was examined by Loss of Heterozygosity (LOH) studies in infiltrating breast carcinoma (n=60), ductal carcinoma in situ (DCIS) (n=10) and benign breast disease (n=5) patients, to determine its possible association with tumor progression.
Methods: LOH at the WT1 locus (11p13) as determined by PCR-RFLP for Hinf1 restriction site and was subsequently examined for its association with intratumoral expression of various growth factors i.e. TGF-β1, IGF-II, IGF-1R and angiogenesis (VEGF and Intratumoral micro-vessel density) in breast carcinoma.
Results: Six of 22 (27.2%) genetically heterozygous of infiltrating breast carcinoma and 1 of 4 DCIS cases showed loss of one allele at WT1 locus. Histologically, the tumors with LOH at WT1 were Intraductal carcinoma (IDC) and were of grade II and III. There was no correlation in the appearance of LOH at WT1 locus with age, tumor stage, menopausal status, chemotherapy status and lymph node metastasis. The expression of factor IGF-II and its receptor, IGF-1R was significantly higher in carcinoma having LOH at WT1 locus. A positive correlation was observed between the TGF-β1, VEGF expression and IMD scores in infiltrating carcinoma.
Conclusions: The current study indicates that the high frequency of loss of allelic integrity at Wilms′ tumor suppressor gene-1 locus in high-graded breast tumors is associated with aggressiveness of the tumor.

Keywords
Ductal carcinoma in situ, insulin-like growth factor II, transforming growth factor β, vascular endothelial growth factor, Wilms′ tumor suppressor gene

 
© Copyright 2009 Indian Journal of Cancer.
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