title: Caveolin-3 is a sensitive and specific marker for rhabdomyosarcoma.
abstract: Caveolin-3 (Cav-3) is a principal structural protein of caveolae membrane domains. Animal studies have revealed that Cav-3 is expressed in skeletal and cardiac myocytes but absent in other types of cells. Recent studies have shown that abnormalities in the Cav-3 gene are associated with some forms of muscular dystrophy, while skeletal muscle abnormalities have been observed in Cav-3 transgenic and knockout mice. In this study the authors evaluated the distribution of Cav-3 in normal human tissues and compared the expression of Cav-3 with that of myogenin and myoD1 in rhabdomyosarcoma (RMS), malignant mixed mullerian tumor (MMMT), and an array of neoplasms that mimic RMS to assess the utility of Cav-3 as a diagnostic marker for tumors with skeletal muscle differentiation. In nonneoplastic human tissues, crisp membrane staining for Cav-3 was present in cardiac and skeletal myocytes and occasionally in arterial smooth muscle cells and prostatic stromal cells, while other cell types were negative for Cav-3. Eighty-eight percent (21/24) of RMS studied were positive for Cav-3. Positive staining was generally observed in the more maturely differentiated tumor cells but not the primitive tumor cells. Eight of nine cases of MMMT stained strongly with Cav-3 in their rhabdomyosarcomatous component but not in other components. Fifty-four other neoplasms (13 leiomyosarcomas, 8 neuroblastomas, 5 lymphomas, 6 Wilms tumors without skeletal muscle differentiation, 5 Ewing sarcomas, 4 malignant fibrous histiocytomas, 4 angiosarcomas, 6 malignant melanomas, and 3 synovial sarcomas) were negative for Cav-3 expression. Nearly all (96% [23/24]) cases of RMS were positive for myogenin, while 88% (21/24) were positive for myoD1. Primitive tumor cells showed significantly increased expression of myoD1 and myogenin; conversely, more differentiated tumor cells were negative or weakly stained. The rhabdomyosarcomatous component of MMMT stained focally with myogenin and myoD1, in contrast to the strong Cav-3 labeling in these cells. These results demonstrate that Cav-3 is specifically expressed in human cardiac and skeletal myocytes. Furthermore, its high specificity and relatively high sensitivity (88%) for tumors with skeletal muscle differentiation suggest that Cav-3 is a valuable marker for these tumors and may be used to assess the degree of differentiation of RMS and to identify residual tumor cells in post-chemotherapy specimens.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, New York, New York 10467,USA.
authors.forename: Samson W
authors.initials: SW
authors.lastname: Fine
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Maomi
authors.initials: M
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D006801:Humans; D018200:Mixed Tumor, Mullerian / Q000737:chemistry / Q000175:diagnosis; D032342:Muscle Cells / Q000737:chemistry; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology; D017570:MyoD Protein / Q000032:analysis; D018008:Myogenin / Q000032:analysis; D012208:Rhabdomyosarcoma / Q000737:chemistry / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018008:Myogenin