Elevated frequency of loss of heterozygosity of PTEN and p53 in breast carcinoma with HER2/neu overexpression

Abstract

9607 Background: Loss of heterozygosity (LOH) of loci of tumor suppressor genes, such as p16INK4A/p15INK4B, was frequently observed in mouse manmmary tumor virus (MMTV) /neu transgenic mice. The purpose of this study is to investigate the relationship between HER2/neu overexpression and the LOH of the major tumor suppressor genes in human breast carcinoma. Methods: Pairs of primary breast carcinoma tissues and corresponding normal tissues were obtained from 108 Japanese women who underwent surgery in our department. LOH of the loci of two major tumor suppressor genes, p53 and PTEN, was analyzed using the automated sequencer. The expression of HER2/neu in breast cancer tissues was evaluated by automated immunohistochemical method. The relationship between HER2/neu overexpression and the LOH of PTEN and p53 gene was examined. Correlation between LOH of PTEN or p53 locus and other clinico-pathological values was also examined. Results: Overexpression of HER2/neu was observed in 32 samples (29.6 %). LOH of PTEN locus was positive in 15 (13.9 %) in 88 informative cases and LOH of p53 locus was positive in 47 (43.5%) in 92 informative cases. LOH of PTEN locus was significantly correlated with the LOH of p53 locus (p=0.0122). LOH of the PTEN and p53 loci was significantly correlated with the overexpression of HER2/neu (p=0.0051, P=0.037). There were no correlation between LOH of PTEN or p53 locus and other clinico-pathological values, such as age, tumor size, clinical stage, axillary lymph node metastases and pathological classification. Conclusion: Frequency of the LOH at loci of PTEN and p53 was significantly high in the breast carcinoma with HER2/neu overexpression. These data suggest that HER2/neu plays an important role in the mechanism of allelic loss of tumor suppressor genes, such as PTEN and p53. No significant financial relationships to disclose.