Abstract

Loss of heterozygosity constitutes a major mechanism of genetic abberations in breast cancer, and strongly indicates the involvement of tumor-suppressor genes in the affected chromosomal regions. Ascertainment and refinement of such deleted regions by highly polymorphic microsatellite markers is a prerequisite for the identification of candidate genes and the isolation of novel genes. Prelimary results from our group indicate the existence of genes located on chromosomal arm 15q that may be involved in breast cancer progression to metastatic stage (Wick et al, Oncogene 1996). In this study a panel of 210 primary breast carcinomas, 28 metastases and 17 local recurrencies from primary breast carcinomas were analyzed for loss of heterozygosity by the use of 16 highly polymorphic markers spanning the chromosomal region 15q11-21. After PCR amplification, microsatellite markers were separated by PAGE. LOH15q was seen in 30 out of 45 (67%) metastases and recurrences, but only in 50 out of 210 (24%) primary tumors (P < 0.01). We identified two subregions defined by microsatellite markers D15S514 (15q15) and CYP19 (15q21.1). LOH15q21.1 was most frequently detected in progressive tumor stages. Importantly, analysis of LOH in several other chromosomal regions (ie BRCA1 and BRCA2, TP53, RB1, ATM) did not demonstrate a general increase in LOH frequencies, indicating that LOH15q is a specific event associated with tumor progression. We are currently analyzing candidate genes located in the regions of interest.

Highlights

  • Lymph node biopsy is important as a prognostic factor, and influences therapy

  • In this study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis

  • This study was undertaken to determine the effect of wound healing drainages and postsurgical sera obtained from breast carcinoma (BC) patients on proliferation of dormant BC cells and to assess the role of HER2 oncoprotein in this proliferation

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Summary

Introduction

Lymph node biopsy is important as a prognostic factor, and influences therapy. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma, the net growth of epithelial cells results from a growth imbalance in favour of proliferation. The objective of this study was to assess the efficacy of hyperbaric oxygen therapy in symptomatic patients after breast cancer treatment. Conclusion: Hyperbaric oxygen therapy should be considered as a treatment option for patients with persisting symptomatology following breast-conserving therapy. We hypothesized that COX-2 expression was associated with that of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) in human breast cancer. Conclusion: COX-2 expression is significantly associated with increased cellular proliferation and angiogenesis in invasive breast cancer. Recent studies have demonstrated that the sentinel node biopsy (SNB) is a reliable and minimally invasive method for determining the axillary node status in patients with breast cancer. Conclusion: Overexpression of episialin strongly inhibits fat secretion, and critically affects timing of involution of the lactating mammary gland

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