Core biopsy diagnosis of ductal carcinoma in situ: an indication for sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a minimally invasive, accurate method of evaluating axillary lymph nodes in patients with invasive cancer. The technique has also been applied successfully in patients with ductal carcinoma in situ (DCIS). The purpose of this study was to review our experience performing SLNB in patients with a biopsy diagnosis of DCIS. METHODS: A prospective study of consecutive patients seen at our institution from August 2001 to April 2004 with a biopsy diagnosis of DCIS was undertaken. Demographic data, biopsy method, final pathology, and surgical treatment were recorded. Patients undergoing SLNB were identified, and pathologic results were noted. RESULTS: Eighty-five patients with a biopsy diagnosis of DCIS were treated. Fifty-five (64.7%) had their diagnosis made by excisional biopsy, and 30 (35.3%) by core biopsy. Forty-four (51.7%) patients underwent SLNB as part of their definitive surgical procedure, and an SLN was successfully identified in 41 (93.2%). Nine (22.0%) patients who underwent successful SLNB had a positive SLN, 2 by hematoxylin and eosin (H&E) staining and 7 by immunohistochemical (IHC) staining for cytokeratin. Both patients with H&E-positive SLN were ultimately found to have invasive disease in their primary lesion. Final pathologic assessment of all primary lesions revealed invasive carcinoma in 7, 6 of whom had their diagnosis made by core biopsy. Overall, 20.0% of patients with a core biopsy diagnosis of DCIS were upstaged to invasive disease. Whether the lesion was palpable, grade and the presence or absence of necrosis were not significantly different in patients ultimately found to have invasive disease versus those who did not. DISCUSSION: Sentinel lymph node biopsy can be performed accurately in patients with a biopsy diagnosis of DCIS. The rate of axillary disease in patients with pure, completely resected DCIS is low; therefore, SLNB is not indicated in all patients with this biopsy diagnosis. Because of a high rate of invasive disease on the final pathology of patients with DCIS diagnosed by core biopsy, these patients should be offered SLNB.

High-throughput proteomic analysis of human infiltrating ductal carcinoma of the breast.

Large-scale proteomics will play a critical role in the rapid display, identification and validation of new protein targets, and elucidation of the underlying molecular events that are associated with disease development, progression and severity. However, because the proteome of most organisms are significantly more complex than the genome, the comprehensive analysis of protein expression changes will require an analytical effort beyond the capacity of standard laboratory equipment. We describe the first high-throughput proteomic analysis of human breast infiltrating ductal carcinoma (IDCA) using OCT (optimal cutting temperature) embedded biopsies, two-dimensional difference gel electrophoresis (2-D DIGE) technology and a fully automated spot handling workstation. Total proteins from four breast IDCAs (Stage I, IIA, IIB and IIIA) were individually compared to protein from non-neoplastic tissue obtained from a female donor with no personal or family history of breast cancer. We detected differences in protein abundance that ranged from 14.8% in stage I IDCA versus normal, to 30.6% in stage IIB IDCA versus normal. A total of 524 proteins that showed > or = three-fold difference in abundance between IDCA and normal tissue were picked, processed and identified by mass spectrometry. Out of the proteins picked, approximately 80% were unambiguously assigned identities by matrix-assisted laser desorbtion/ionization-time of flight mass spectrometry or liquid chromatography-tandem mass spectrometry in the first pass. Bioinformatics tools were also used to mine databases to determine if the identified proteins are involved in important pathways and/or interact with other proteins. Gelsolin, vinculin, lumican, alpha-1-antitrypsin, heat shock protein-60, cytokeratin-18, transferrin, enolase-1 and beta-actin, showed differential abundance between IDCA and normal tissue, but the trend was not consistent in all samples. Out of the proteins with database hits, only heat shock protein-70 (more abundant) and peroxiredoxin-2 (less abundant) displayed the same trend in all the IDCAs examined. This preliminary study demonstrates quantitative and qualitative differences in protein abundance between breast IDCAs and reveals 2-D DIGE portraits that may be a reflection of the histological and pathological status of breast IDCA.

High-throughput loss of heterozygosity mapping in 26 commonly deleted regions in breast cancer.

Capillary array electrophoresis and laser-assisted microdissection, which provide increased speed and accuracy in loss of heterozygosity studies, are often used independently in studying breast cancer; the successful coupling of these emerging technologies, however, must overcome technical problems, especially those related to the poor quality and quality of DNA typically retrieved from archival tumor samples. Here we present a panel of 52 microsatellite markers from 26 of the most commonly deleted regions in breast cancer. All markers have been optimized to robustly amplify DNA extracted from paraffin-embedded samples, represent informative (highly polymorphic) loci, and effectively detect chromosomal loss. In the 10 tumor samples (stage 0 to stage III) tested here, chromosomal loss was detected loss for every locus, and the degree of loss at the 26 commonly deleted regions ranged from 23% to 77%. This panel can be used to quickly detect genomic patterns of loss in large numbers of breast tumor samples and may provide both clinical information and molecular information regarding the underlying tumor suppressor genes.