Caveolae are cholesterol enriched invaginations of the plasma membrane involved in a variety of processes, including glucose and fatty acids absorption, cell transduction and mechanoprotection. The biogenesis and function of caveolae depend on the activity of Caveolin (Cav-1, -2 and -3) and Cavin (Cavin-1, -2, -3 and -4) protein families. Since the membrane Cavin-2 protein was reported to play a key role in caveolae formation of adipocytes, in this work we have used a multidisciplinary approach to investigate its expression in liposarcoma (LPS), an adipocytic soft tissue sarcoma affecting adults. Data obtained through an in silico and immunohistochemical analysis suggest that Cavin-2, along with Cavin-1, Cav-1 and Cav-2, is mostly expressed in the least aggressive LPS subtype, namely well-differentiated LPS, while is almost undetectable in the more aggressive myxoid, pleomorphic and dedifferentiated LPS tumors. Accordingly, in vitro analysis confirmed that Cavin-2 expression increases in LPS tumor cell lines during differentiation as compared to proliferation, as detected by immunoblotting and immunofluorescence analysis. Overall, these data suggest that Cavin-2 represents a useful marker for discriminating the degree of differentiation in LPS tumors. (C) 2017 Elsevier Inc. All rights reserved.