Molecular Genetic Analysis of Rhabdomyosarcoma and its Pathologic Differential Diagnosis

横纹肌肉瘤（RMS）是一种高度恶性的软组织肉瘤，通常发生在儿童时期。RMS的诊断依赖于骨骼分化的识别，然而，用传统的组织学技术有时很难将RMS与其他肉瘤区分开来。我们研究了RMS病例的免疫组织化学特征和分子分析。免疫组化检查结果显示，大多数横纹肌肉瘤细胞的促球蛋白和肌动蛋白阳性，但在少数肿瘤细胞中检测到肌红蛋白。CD99 （MIC2基因产物）在70%的RMS病例中呈弱阳性。这些结果表明，与肌红蛋白和CD99相比，desmin和肌粘连肌动蛋白是更有价值的RMS标志物。肺泡型RMS与特异性易位t（2; 13）和t（1; 13）相关，导致融合基因PAX3-FKHR和PAX7-FKHR。我们在所有肺泡性RMS病例中检测到PAX3-FKHR或PAX7-FKHR融合转录本。而在恶性淋巴瘤、尤文氏肉瘤/PNET家族、恶性纤维组织细胞瘤和胚胎性RMS中未见嵌合基因融合。在组织学上由多形梭形细胞和肿瘤巨细胞组成而不存在肺泡模式的7个多形RMSs中，1个显示嵌合PAX3-FKHR基因。这一证据表明，肺泡型和多形性RMS在肿瘤发生机制上有特定的相似性。

Rhabdomyosarcoma (RMS) is a highly malignant soft-tissue sarcoma that usually occurs in childhood. The diagnosis of RMS depends on the identification of skeletal differentiation, however, with conventional histologic techniques it is sometimes difficult to distinguish RMS from other sarcomas. We have studied the immunohistochemical characteristics and molecular analysis in RMS cases.In the results of immunohistochemical studies most of rhabdomyosarcoma cells were positive for desmin and sarcomeric actin, but myoglobin was detected in a few tumor cells. CD99 (MIC2 gene product) was weakly positive in 70% of RMS cases. These results suggest that desmin and sarcomeric actin are more valuable markers for RMS than myoglobin and CD99.Alveolar type RMS is associated with specific translocations, t(2 ; 13) and t(1 ; 13), resulting in the fusion genes PAX3-FKHR and PAX7-FKHR. We detected the PAX3-FKHR or PAX7-FKHR fusion transcripts in all cases of alveolar RMS cases. However, there were no chimeric gene fusions in cases of malignant lymphoma, Ewing's sarcoma/PNET family, malignant fibrous histocytoma and embryonal RMS. One of seven pleomorphic RMSs which were histologically composed of pleomorphic spindle cells and tumor giant cells without the presence of alveolar pattern, showed the chimeric PAX3-FKHR gene. This evidence suggests a specific similarity in the mechanism of tumorgenesis between tumors classified as alveolar and pleomorphic RMS.