石蜡包埋软组织肉瘤中融合基因表达的检测及其诊断学价值

Diagnostic significance and clinical application of specific chimeric genes in soft tissue sarcomas by RT-PCR using paraffin-embedded tissues:a study of 103 specimens

目的 探讨检测软组织肉瘤组织中特异性染色体易位融合基因表达的诊断学意义。方法 运用一步法RT PCR技术检测 10 5例石蜡包埋软组织肉瘤 ,包括 30例滑膜肉瘤、15例横纹肌肉瘤(RMS)、2 5例尤因肉瘤 /外周原始神经外胚层瘤 (ES/pPNET)、12例隆突性皮肤纤维肉瘤 (DFSP)、14例腺泡状软组织肉瘤 (ASPS)、3例平滑肌肉瘤 (LMS)、2例恶性纤维组织细胞瘤 (MFH)、2例纤维肉瘤和2 0例对照组肿瘤组织中特异性染色体易位融合基因SSX1/SSX2 SYT、PAX3/PAX7 FKHR、EWS FLI1、COL1A1 PDGFB、ASPL TFE3的表达。结果 30例滑膜肉瘤中 ,2 8例 ( 93 3% )检出SYT SSX融合基因的表达 ,其中 14例表达SYT SSX1,9例表达SYT SSX2 ;6例腺泡型RMS 4例表达PAX3/PAX7 FKHR ,其余9例胚胎型和多形性RMS均无PAX FKHR表达 ;80 % ( 2 0 / 2 5 )的ES/pPNET中表达EWS FLI1或EWS ERG ;12例DFSP中 8例 ( 6 7% )检出COL1A1 PDGFB融合基因的表达 ,14例ASPS中 10例 ( 71% )检出融合基因ASPL TFE3的表达。 3例LMS、2例MFH、2例纤维肉瘤和对照组 2 0例肿瘤组织中均未检出上述易位融合基因的表达。结论 软组织肉瘤特异性染色体易位融合基因的表达是其分子诊断的可靠指标 ,一步法RT PCR技术检测染色体易位融合基因为临床软组织肉瘤疑难病例的诊断?

Objective To investigate the expression of the chimeric genes resulting from the specific chromosomal translocations in soft tissue sarcomas (STS) and its diagnostic significance for STS. Methods The variety of fusion transcripts were detected in 103 cases of STS, including 30 cases of synovial sarcoma (SS), 15 cases of rhabdomyosarcoma (RMS), 25 cases of Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET), 12 cases of dermatofibrosarcoma protuberans (DFSP), 14 cases of aveolar soft part sarcoma (ASPS), 3 cases of leiomyosarcoma (LMS), 2 cases of malignant fibrous histocytoma (MFH), and 2 cases of fibrosarcoma (FS); and 20 cases of control tumors by reverse transcription polymerase chain reaction (RT PCR) using formalin fixed, paraffin embedded specimens. Results Of the 34 cases of SS 28 (93.3%) expressed SSX SYT chimeric transcripts (14 were positive for SYT SSX1,9 for SYT SSX2). Four of the six cases of alveolar RMS had a PAX3/ PAX7 FKHR fusion transcript. None of the 9 cases of embryonic and polymorphic RMS expressed PAX3/PAX7 FKHR. Of the 25 cases of ES/pPNET, 19 were positive for EWS FLI1 fusion transcript and 1 for EWS ERG fusion transcript. COL1A1 PDGFB fusion transcript was expressed in 8 of the 12 cases (66.7%) of DFSP. Of the fourteen cases of ASPS, ten expressed ASPL TFE3 fusion transcript. None of the 3 cases of LMS, 2 cases of MFH, 2 cases of FS, and 20 control cases contained any of the fusion transcript. Conclusion Chimericgene transcript resulting from specific chromosomal translocations is a reliable index for the molecular diagnosis of STS and RT PCR assay for detection of specific fusion gene provides a useful tool for confirmation of the diagnosis of STS in diagnostically difficult cases and in retrospective studies.