p16 Immunohistochemistry is Less Useful Than MDM2 and CDK4 to Distinguish Dedifferentiated Liposarcomas From Other Retroperitoneal Mimics.

Dedifferentiated liposarcoma (DDL) frequently involves the retroperitoneum. In the absence of a lipogenic component histologically, the differential diagnosis of a retroperitoneal DDL includes other sarcomas and, if the tumor has visceral involvement, sarcomatoid carcinoma. DDL demonstrates amplification of chromosome subregion 12q13-q15. Detection of the amplification itself, or the resulting overexpression of the MDM2 and CDK4 genes by genetic and immunohistochemical methods, is a useful ancillary test in the diagnosis of DDL. More recently, immunohistochemistry for p16, the product of the CDKN2A gene, was shown to be a useful adjunct in differentiating well-differentiated liposarcoma from benign adipocytic tumors. In the present study, we examined the utility of p16 immunohistochemistry to distinguish DDL (n=44) from other high-grade and low-grade retroperitoneal mimics (n=73). p16 positivity was observed in 43/44 (98%) DDLs, with the majority of these showing strong, diffuse, staining. The rate of p16 positivity in other retroperitoneal tumors was lower (37/73, 51%) and staining was not as consistently diffuse or intense. Furthermore, p16 positivity varied between the control sarcomas based on tumor type as follows: 11/11 leiomyosarcomas, 8/11 pleomorphic undifferentiated sarcomas, 9/39 sarcomatoid carcinomas, 7/7 desmoid tumors, 1/3 endometrial stromal sarcomas, and 1/2 malignant gastrointestinal stromal tumors. On the basis of these findings, we conclude that p16 is highly sensitive for retroperitoneal DDL. However, the lack of specificity limits the diagnostic utility compared with the more established markers MDM2 and CDK4.