Frequency of MDM2 Amplification in Malignant Peripheral Nerve Sheath Tumors: Non-Correlation with Tumor Grade, Cellularity and MIB1 Proliferation Index.
Michelle L Wallander, Lester J Layfield. ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT; University of Utah School of Medicine and ARUP Laboratories, Salt Lake City
Background: The p53 tumor suppressor gene is inactivated by a variety of mechanisms including interaction with the MDM2 oncoprotein. MDM2 is known to be abnormally upregulated in a variety of human neoplasms secondary to gene amplification. Assessment of MDM2 amplification is clinically most useful for the separation of lipomas from atypical lipomatous neoplasms/well differentiated liposarcomas. MDM2 is amplified in liposarcomas but not in lipomas. MDM2 amplification occurs in approximately 7% of all human neoplasms with the highest frequency of amplification being found in soft tissue tumors (20%), osteosarcomas (16%) and esophageal carcinomas (13%). Early studies have indicated that MDM2 is not amplified in malignant peripheral nerve sheath tumors.
Design: Sixteen malignant peripheral nerve sheath tumors and five schwannomas were obtained from the files of the Department of Pathology. These cases underwent fluorescence in situ hybridization analysis for the presence of MDM2 amplification. For each malignant peripheral nerve sheath tumor, assessments were made for cellularity (low or high), percentage of cells staining positively for p53 and percentage of cells staining with MIB-1.
Results: Three of sixteen (19%) malignant peripheral nerve sheath tumors demonstrated amplification of the MDM2 gene. None of the schwannomas demonstrated MDM2 amplification. Malignant peripheral nerve sheath tumors associated with MDM2 amplification demonstrated a MIB1 proliferation index of 39% or greater and all three amplified cases demonstrated a high percentage of cells staining for p53 (18%, 32% and 55%).
Conclusions: Prior studies have failed to demonstrate MDM2 amplification in malignant peripheral nerve sheath tumors. Our study demonstrated that approximately 19% of malignant peripheral nerve sheath tumors display amplification of the MDM2 gene. Malignant peripheral nerve sheath tumors demonstrating MDM2 amplification had a higher than average MIB1 proliferation index and a higher than average percentage of cells staining for p53. MDM2 amplification may represent a method for inactivation of p53 in a subset of malignant peripheral nerve sheath tumors and may result in an increased proliferation index.
Category: Bone & Soft Tissue
Monday, February 28, 2011 1:00 PM
Poster Session II # 16, Monday Afternoon