Utility of p16 in Distinguishing Lipomas and Well-Differentiated Liposarcomas Compared to Fluorescence In-Situ Hybridization
Raul S Gonzalez, Colt M McClain, Ben K Chamberlain, Cheryl M Coffin, Justin M Cates. Vanderbilt University Medical Center, Nashville, TN
Background: Fluorescence In-Situ Hybridization (FISH) for amplification of MDM2 is considered the gold standard assay for the diagnosis of well-differentiated liposarcoma (WDL). It is especially useful in lipoma-like WDL, in which cytologic atypia may be focal. Immunohistochemistry (IHC) for p16 has recently been suggested as a sensitive and specific method for distinguishing these two entities, but it has not been validated on cases in which the diagnosis was confirmed by FISH analysis.
Design: A series of 19 lipoma-like WDL and 21 lipomas in which the diagnosis had been previously confirmed by FISH analysis were stained for p16 by IHC. Nuclear p16 staining was scored according to previously published methods: 0% of cells staining was recorded as negative, 1-10% as focal, 11%-50% as multifocal, and >50% as diffuse. The presence of strong, diffuse cytoplasmic p16 staining was also recorded. Regions of fat necrosis were excluded from evaluation.
Results: Nuclear p16 staining was significantly increased in WDL compared to lipoma (Mann-Whitney, P=<0.0001). Of the 19 WDL, 17 (89%) showed at least multifocal strong staining. In contrast, 18 of 21 lipomas (86%) showed no more than focal strong staining for p16; 3 cases showed multifocal strong staining. ROC analysis indicated maximum diagnostic accuracy (88%) was achieved using multifocal strong staining as the threshold value for defining a positive IHC result. Diagnostic performance parameters using this criterion for nuclear p16 in the diagnosis of WDL are presented in the table below.
|Sensitivity (95% CI)||0.90 (0.67-0.99)|
|Specificity (95% CI)||0.86 (0.64-0.97)|
|Positive likelihood ratio (95% CI)||6.26 (2.17-18.10)|
|Negative likelihood ratio (95% CI)||0.12 (0.03-0.46)|