Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 681
© 2004 American Society of Clinical Oncology

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Abstract

A novel DNA marker associated with breast metastasis

Temple University, Philadelphia, PA; Temple University Hospital, Philadelphia, PA; Temple Fox Chase Cancer Center, Philadelphia, PA; Dept. of Radiation Oncology, Temple University, Philadelphia, PA

681

Background: Differentiating primary breast tumors that are prone to develop metastasis (Group-I) from those that are not (Group-II) is critical to design appropriate treatments. Previously we isolated several metastasis associated DNA sequences (MADSs) and recently published that MADS-IX and -XI are informative in more than 60% of cases by PCR screening. Our previous attempts to supplement the PCR method with Fluorescence In Situ hybridization (FISH) for screening MADS-IX on primary tumor tissue sections were not consistent due to overlapping of cells and unclear cellular margins. Here we present our results with MADS-IX as a FISH probe in distinguishing the Group-I and Group-II primary breast tumors by screening tumor cell touch preparations. Methods: The DNA samples from primary and metastatic tumor cells isolated from 12 breast carcinoma patients had been compared with the matching normal cell DNA by the Representational Difference Analysis (RDA) and isolated 15 MADSs. Tumor cells were isolated by laser capture microdissection from archival samples whose clinical outcome was known. In the tumor cell touch preparation method, the tumor tissue material was exposed by trimming of the paraffin material from the block and then by touching the tumor tissue side at several places on a slide. Conventional methods were used to fix the cells followed by our FISH procedure. We used 3 cases of primary tumors that had positive lymph nodes (LN) and another 3 that had not (within 5 years of treatment). Results: The tumor touch preparations provided with clear and reproducible results. Group-I tumors with +ve LNs showed cells with no loss of MADS-IX in 54%; heterozygous loss in 38% and homozygous loss in 8%. Group-II tumors with –ve LNs, on the other hand showed cells with no loss of MADS-IX in 80%; heterozygous loss in 20% and none with homozygous loss. Conclusions: Basing on these studies, we propose that MADS-IX could be used as a candidate DNA marker to differentiate breast tumors that are prone to develop metastasis from the rest. This finding has a potential for better diagnostic grouping and treatment. Aside from screening additional breast tumors, cDNA expression profiling of the tumors are in progress.

No significant financial relationships to disclose.

Abstract presentation from the 2004 ASCO Annual Meeting