Fine Samson W, Lisanti Michael P, Argani Pedram, Li Maomi
Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, New York, New York 10467,USA.
Appl Immunohistochem Mol Morphol. 2005 Sep;13(3):231-6. doi: 10.1097/00129039-200509000-00003.
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.
小窝蛋白3（Cav-3）是小窝膜结构域的主要结构蛋白。动物研究表明，Cav-3在骨骼肌和心肌细胞中表达，但在其他类型细胞中不存在。最近的研究表明，Cav-3基因异常与某些形式的肌肉营养不良有关，同时在Cav-3转基因和基因敲除小鼠中观察到骨骼肌异常。在本研究中，作者评估了Cav-3在正常人体组织中的分布，并比较了Cav-3与肌细胞生成素及肌分化抗原1（myoD1）在横纹肌肉瘤（RMS）、恶性苗勒管混合瘤（MMMT）以及一系列模仿RMS的肿瘤中的表达，以评估Cav-3作为具有骨骼肌分化肿瘤诊断标志物的效用。在非肿瘤性人体组织中，Cav-3的清晰膜染色见于心肌和骨骼肌细胞，偶尔见于动脉平滑肌细胞和前列腺基质细胞，而其他细胞类型Cav-3呈阴性。研究的RMS中有88%（21/24）Cav-3呈阳性。通常在分化更成熟的肿瘤细胞中观察到阳性染色，而原始肿瘤细胞则无。9例MMMT中有8例在其横纹肌肉瘤成分中Cav-3染色强烈，而其他成分则无。其他54种肿瘤（13例平滑肌肉瘤、8例神经母细胞瘤、5例淋巴瘤、6例无骨骼肌分化的肾母细胞瘤、5例尤因肉瘤、4例恶性纤维组织细胞瘤、4例血管肉瘤、6例恶性黑色素瘤和3例滑膜肉瘤）Cav-3表达呈阴性。几乎所有（96%[23/24]）RMS病例肌细胞生成素呈阳性，而88%（21/24）myoD1呈阳性。原始肿瘤细胞中myoD1和肌细胞生成素表达显著增加；相反，分化程度更高的肿瘤细胞呈阴性或弱染色。与这些细胞中强烈的Cav-3标记相反，MMMT的横纹肌肉瘤成分肌细胞生成素和myoD1呈局灶性染色。这些结果表明，Cav-3在人体心肌和骨骼肌细胞中特异性表达。此外，其对具有骨骼肌分化肿瘤的高特异性和相对较高的敏感性（88%）表明，Cav-3是这些肿瘤的有价值标志物，可用于评估RMS的分化程度，并识别化疗后标本中的残留肿瘤细胞。
