Loss of heterozygosity of the Wilms' tumor suppressor gene (WT1) in in situ and invasive breast carcinoma

The Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, reg ulates the expression of the insulin-like growth factor (IGF) and transform ing growth factor (TGF) systems, both of which are implicated in breast tum orignesis. WT1 allelic integrity was examined by loss of heterozygosity (LO H) studies in formalin-fixed, paraffin-embedded (FFPE) ductal carcinoma in. situ (DCIS, n = 20) and fresh frozen primary invasive breast carcinomas (n = 24). Loss of heterozygosity (LOH) at the WT1 locus (11p13) was examined by PCR evaluation of an Hinf1 restriction fragment length polymorphism (RFL P) and correlated to tumor stage (in situ and invasive). After identificati on of the heterozygous/informative breast lesions, 1 of 12 (8.3%) DCIS (hig h-grade micropapillary) and 3 of 14 (21.4%) of infiltrating carcinomas (hig h grade) showed loss of one allele, suggesting that LOH of the WT1 locus is a rare genetic event in early breast cancer, becoming more common in invas ive and in high-grade lesions. Copyright (C) 1999 by W.B. Saunders Company.