Abstract 1757: Patterns of clonal chromosomal aberrations in invasive breast cancer compared to adjacent DCIS lesions detected by a ten-probe FISH panel

Abstract

Abstract Ductal carcinoma in situ (DCIS) refers to lesions with malignant epithelial cells that have not invaded the surrounding stroma. These lesions are confined to the ducts of the breast. It is thought that DCIS represents a stage that precedes invasive ductal carcinoma (IDC). However the linkage between these two lesions is still obscure. In order to analyze the patterns of genetic alterations as an approach to understand the correlation between DCIS and IDC, we developed four panels of FISH probes consisting of a total of eight gene specific probes and two centromeric probes and conducted a systematic FISH evaluation of breast tumor specimens containing both lesions. The gene probes tested for oncogenes and tumor suppressor genes specific for breast tumorigenesis while the centromeric probes were included to reflect and adjust for the ploidy of the cells. Objectives Determine gain and loss patterns of the oncogene and tumor suppressor gene probes within DCIS and IDC Compare similarities in the genetic make-up of DCIS and corresponding IDC lesions from the same case Characterize clonal evolution from DCIS lesions to IDC The database of the “Breast Susceptibility Study” conducted at the Naval Medical Center, Bethesda, Maryland was searched for patients whose pathology reports were positive for breast carcinoma with neighboring DCIS. Archived paraffin blocks were analyzed by a pathologist for the presence of invasive cancer and DCIS. Representative areas were marked on thick sections. The material was micro-dissected and disintegrated using the Hedley method. The resulting single cell suspensions were cytospun onto slides. The best cytospin for each lesion was. hybridized with four FISH probe panels subsequently. An Imaging relocation software allowed us to assess the same cells for all four sets of probes. For each lesion, manual counting of 150-200 nuclei was performed and tabulated into an excel spreadsheet to allow analysis of signal patterns. In collaboration with NCBI, algorithms were developed to compare clonal patterns. Preliminary data show that there are often major clones both in the DCIS and the IDC that present strong similarities to each other. However, the clones can differ in specific gains or losses of the oncogenes and tumor suppressor genes tested. The signals depicted in the table represent an attempt to delineate major clones within the DCIS and IDC populations. This study will improve our understanding of the molecular events that are involved in the progression from pre-invasive to invasive cancer and may lead to the development of prognostic biomarkers that can predict this transition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1757.