Molecular Genetic Analysis of Rhabdomyosarcoma and its Pathologic Differential Diagnosis

横纹肌肉瘤的分子遗传学分析及其病理鉴别诊断

• 批准号: 13670193
• 负责人: NOJIMA Takayuki
• 金额: $ 2.24万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670193/
• 关键词: Rhabdomyosarcoma; Malignant soft tissue tumors; PAX gene; FKHR gene; Chimeric gene; Pathologic diagnosis; 悪性線維性組織球腫; 悪性線維性組織球腫肉腫

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.

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鉴定，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。我们对RMS的免疫组织化学特征和分子分析进行了研究，免疫组织化学结果显示大部分横纹肌肉瘤细胞呈结蛋白和肌节肌动蛋白阳性，少数肿瘤细胞可检测到肌红蛋白。70%的RMS患者CD99(MIC2基因产物)弱阳性。这些结果表明，结蛋白和肌节肌动蛋白是RMS比肌红蛋白和CD99更有价值的标志物，肺泡型RMS与t(2；13)和t(1；13)特定易位相关，导致融合基因PAX3-FKHR和PAX7-FKHR。我们在所有肺泡型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家系、恶性纤维组织细胞瘤和胚胎期RMS中均未发现嵌合基因融合。组织学上由多形性梭形细胞和肿瘤巨细胞组成的7个多形性RMS中有1个显示了PAX3-FKHR嵌合基因。这一证据表明，肺泡型和多形性RMS在肿瘤发生机制上有特殊的相似性。

项目成果

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T.Suzuki: "Co-expression of interleukin-1β and tumor necrosis factor α in synovial tissues and synovial fluids of temporomandibular joint with internal derangement. Comparison with histological grading of synovial inflammation"J Oral pathol Med. 31. 549-5

T.Suzuki：“内部紊乱的颞下颌关节滑液组织和滑液中白细胞介素 1β 和肿瘤坏死因子 α 的共表达。与滑膜炎症的组织学分级的比较”J Oral pathol Med 31. 549-5。

T.Suzuki: "Co-expression of interleukin-1β and tumor necrosis factor α in synovial tissues and synovial fluids of temporomandibular joint with internal derangement. Comparison with histological grading of synovial inflammation"J. Oral Pathol. Med.. 31. 54

T.Suzuki：“内部紊乱的颞下颌关节滑液组织和滑液中白细胞介素 1β 和肿瘤坏死因子 α 的共表达。与滑膜炎症的组织学分级的比较”J. Oral Pathol。

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A.Gordon：“多形性横纹肌肉瘤中的染色体失衡以及一例肺泡型横纹肌肉瘤相关 PAX3-FOXO1A 融合基因的鉴定”《Cancer Genet Cytogenet》。

W-Q, Sheng: "Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues"Am J Clin Pathol. 115・3. 348-355 (2001)

W-Q，盛：“先天性婴儿纤维肉瘤。10例临床病理学研究和使用石蜡包埋组织的ETV6-NTRK3融合转录本的分子检测”Am J Clin Pathol 115・3（2001）。