MDM2 Copy Numbers in Well Differentiated and Dedifferentiated Liposarcoma: Where Do We Draw the Line?
Patrick Ware, Anthony Snow, Mark Pettenati, Shadi Qasem. Wake Forest University Baptist Medical Center, Winston Salem
Background: MDM2 gene amplification is a known molecular abnormality associated with specific liposarcomas. Most recently, this amplificiation has been shown to be helpful in differentiating benign lipoamtous neoplasms from well differentiated (WDL) and dedifferentiated liposarcomas (DDL). A ratio of MDM2 copy number to CEP12 signal greater than 2 has been shown to be diagnostic of amplification and malignancy. What has not been established is the trend in variation of MDM2 copy numbers between WDL and DDL. The purpose of this study is to determine if DDL has higher amplification of MDM2 copy numbers as compared to WDL using FISH analysis.
Design: A total of 50 samples were analyzed; 26 WDL, 14 DDL and 10 control cases. The cases were reviewed for appropriate diagnosis. We also looked at borderline areas, myxoid areas and areas of possible low grade dedifferentiation. FISH for MDM2 and CEP12 was conducted on all specimens. The total MDM2 copy number per cell as well as the ratio of MDM2 copy number to CEP12 signals, were determined for each case. Negative controls included benign lipomatous neoplasms as well as mxyoid liposarcomas.
Results: 50 samples were reviewed from 43 patients, 27 men and 16 women and a mean age of 59 (22-86). MDM2/cell in the WDL cases had a mean of 24.5 (5.2-39.14) and the DDL cases had a mean of 39.5 (29.5-60) [p-value= 0.0002]. The MDM2/CEP12 ratio in the WDL cases had a mean of 12.1 (2.4-22.2) and the DDL cases had a mean of 20 (17-27) [p value= 0.00001]. Interestingly, in evaluating borderline areas when compared to WDL, albeit the small number of cases studied (n=4), they also showed significantly higher rate of MDM2 amplification (mean MDM2/cell = 35.7; mean ratio = 19.5). All negative controls showed no amplification of the MDM2 gene (MDM2/CEP12 ratio<2).
|Mean MDM2/Cell [CI]||Mean MDM2/CEP12 Ratio [CI]|
|WDL||24.5 [21-28]||12.1 [9.7-14.5]|
|DDL||39.5 [34.4-44.6]||20.0 [17.8-22.2]|