Objective: To investigate the role of JAZF1 gene rearrangement in the diagnosis and differential diagnosis of endometrial stromal sarcomas by fluorescence in situ hybridization (FISH). Methods: JAZF1 gene rearrangement was analyzed by FISH in 129 cases of ESS diagnosed from January 2008 to December 2016 including 105 cases of low-grade endometrial stromal sarcoma (LG-ESS), 21 cases of high-grade endometrial stromal sarcoma (HG-ESS) and 3 cases of undifferentiated uterine sarcoma (UUS). Sixteen cases of the related tumours in uterus were also collected as control group. The results were compared with our previous studies of JAZF1/JJAZ1 fusion gene in ESS by RT-PCR. Results: Detection of JAZF1 gene rearrangement by FISH was successfully analyzed in 144 cases. JAZF1 gene alteration was detected in 63 cases, all of which were LG-ESS, with an overall positivity of 60.6% (63/104), while no JAZF1 gene rearrangement was found in all other cases. JAZF1 gene rearrangement was present in LG-ESS with classic histology (69.3%, 52/75), smooth muscle differentiation (2/10), sex cord-like differentiation (4/5), fibromyxoid change (1/5), clear cell change (0/1), skeletal muscle differentiation (0/1), and schwannoma-like palisading pattern (0/1). The different components in all the cases of LG-ESS with variant histology had the clonal origin, with or without JAZF1 gene alteration. Compared to the results of JAZF1/JJAZ1 fusion gene by RT-PCR, the positive rate of JAZF1 gene rearrangement in LG-ESS by FISH (61.9%, 26/42) was significantly higher than that of RT-PCR (30.0%, 12/40; P<0.01). Conclusions: JAZF1 gene rearrangement is present only in LG-ESS, but not in HG-ESS, UUS or other related tumours in uterus. The frequency of JAZF1 gene rearrangement varies between classic LG-ESS and different morphologic variants. It is frequently, but not consistently, present in classic LG-ESS and less often positive in variant cases. The results of JAZF1 gene alterations in LG-ESS with different morphologic variants support the contention that the endometrial stromal and their variant morphologic components have the same clonal origin. Detection of JAZF1 gene rearrangement by FISH is very useful for the diagnosis and differential diagnosis of ESS.
目的： 探讨荧光原位杂交(FISH)法检测JAZF1基因易位在子宫内膜间质肿瘤诊断与鉴别诊断中的应用价值。 方法： 收集2008年1月至2016年12月病理确诊的子宫内膜间质肿瘤129例患者资料，包括低级别子宫内膜间质肉瘤(LG-ESS)105例、高级别子宫内膜间质肉瘤(HG-ESS)21例和未分化子宫肉瘤3例，同时收集子宫其他梭形细胞肿瘤16例。采用FISH法检测上述病例的JAZF1基因易位情况，并与既往应用逆转录聚合酶链反应(RT-PCR)法检测JAZF1/JJAZ1融合基因的结果进行比较。 结果： FISH法成功检测了144例样本(包括104例LG-ESS)中JAZF1基因易位情况，其中63例检出JAZF1基因易位，均为LG-ESS。LG-ESS中JAZF1基因易位的总体阳性率为60.6%(63/104)。在伴有不同组织学形态的LG-ESS中，JAZF1基因易位的阳性比例分别为：经典亚型69.3%(52/75)、子宫内膜间质结节/LG-ESS 4/6、伴平滑肌分化2/10、伴性索分化4/5、伴纤维黏液样变1/5、伴透明细胞变0/1、伴横纹肌样分化0/1、伴神经鞘瘤样栅栏状排列0/1。在LG-ESS的各种组织学变异亚型中，不同组织形态学区域的肿瘤细胞具有相同的遗传学改变，均有或无JAZF1基因易位。在43例LG-ESS中，1例FISH检测失败，3例RT-PCR法检测失败。FISH与RT-PCR法检测JAZF1基因改变的阳性率分别为61.9%(26/42)和30.0%(12/40)，差异具有统计学意义(P<0.01)。 结论： JAZF1基因易位相对特异地发生于LG-ESS, LG-ESS各种组织学亚型中JAZF1基因易位阳性率存在差异，其中具有经典形态的LG-ESS易位阳性率较高。JAZF1基因检测结果提示子宫内膜间质肿瘤细胞与其特殊形态变异细胞具有相同起源，支持单克隆学说。应用FISH法检测JAZF1基因易位在子宫内膜间质肿瘤的诊断与鉴别诊断中具有重要意义。.
Keywords: In situ hybridization, fluorescence; Reverse transcriptase polymerase chain reaction; Sarcoma, endometrial stromal; Translocation, genetic.