Low Level MDM2 Gene Amplification and MDM2 Polysomy Are Found in Extra-Uterine and Uterine Leiomyosarcoma by Fluorescence In Situ Hybridization (FISH) Analysis
SJ Hwang, HC Hwang, CH Tse, LC Goldstein, AM Gown. State University of New York(SUNY) Stony Brook, Stony Brook, NY; PhenoPath Laboratories, Seattle, WA
Background: Assessment of MDM2 gene copy number by fluorescence in situ hybridization (FISH) analysis is of particular diagnostic utility in the setting of well-differentiated and de-differentiated liposarcoma, which exhibit MDM2 amplification, and in pleomorphic lipoma, which exhibits MDM2 polysomy. Although many non-lipomatous mesenchymal tumors have been shown to lack MDM2 alterations, leiomyosarcomas have not been well-characterized with regard to MDM2. The purpose of this study was therefore to examine both uterine and extra-uterine leiomyosarcoma for the presence of MDM2 gene copy number alterations by FISH.
Design: Archived formalin fixed paraffin embedded tissue blocks for 9 cases of uterine leiomyosarcoma and 8 cases of extra-uterine leiomyosarcoma were identified from case records. After deparaffinization and enzyme treatment, whole tissue cut sections of cases were incubated with a dual color FISH probe cocktail containing a labeled probe to the MDM2 genomic locus and a labeled probe to the centromeric region of chromosome 12 (SE12). High power images of probed sections were captured with a Metasystems image analysis system. MDM2 and SE12 FISH signals were then enumerated on 50 DAPI stained nuclei for each case and MDM2:SE12 ratios calculated. Tumors were scored for the presence of MDM2 amplification (MDM2:SE12 ratio ≥2.0) and MDM2 polysomy (MDM2 ≥ 3.0, MDM2:SE12 < 2.0).
Results: The average MDM2 signals, SE12 signals and MDM2:SE12 ratio (with ranges in parentheses) for the uterine leiomyosarcomas were 4.2 (2.4-10.1), 3.4 (2.0-6.0), and 1.2 (0.7-1.8), and for the extra-uterine leiomyosarcomas were 2.8 (1.8-4.2), 2.2 (1.7-2.9), and 1.3 (0.7-2.1), respectively. Low level MDM2 amplification was found in 2/8 (25%) extrauterine cases (MDM2:SE12 ratio 2.0 and 2.1) and 0/9 (0%) uterine cases. MDM2 polysomy was found in 1/8 (12.5%) extrauterine cases and 5/9 (55%) uterine cases.
Conclusions: Low level amplification of MDM2 and MDM2 polysomy were seen in extra-uterine and uterine leiomyosarcomas, respectively. The uterine leiomyosarcomas generally had higher MDM2 gene copies than the extra-uterine tumors, although a subset of the extra-uterine tumors exhibited low level amplification, which was not found in the uterine tumors. Caution should therefore be exercised in diagnostic MDM2 FISH evaluation of spindle cell tumors.
Category: Bone & Soft Tissue
Monday, March 22, 2010 1:00 PM
Poster Session II # 22, Monday Afternoon