Objective: To investigate the diagnostic value of detecting MDM2 gene amplification by fluorescence in situ hybridization (FISH) in low-grade osteosarcoma (LGOS). Methods: Thirty cases of parosteal osteosarcoma (POS) and 14 cases of low-grade central osteosarcoma (LGCOS) from April 2009 to August 2022 at Beijing Jishuitan Hospital, Capital Medical University were analyzed for the presence of MDM2 gene amplification by FISH. Fifty-eight additional cases were used as negative controls (including 28 cases of fibrous dysplasia, 5 cases of giant cell tumor, 4 cases of conventional osteosarcoma, 2 cases each of periosteal osteosarcoma, reparative changes after fracture, pleomorphic undifferentiated sarcoma, low grade myofibroblastic sarcoma, fibrous dysplasia with malignant transformation, one case each of leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant peripheral nerve sheath tumor, desmoplastic fibroma of bone, solitary fibrous tumor, aneurysmal bone cyst, clear cell chondrosarcoma, osteofibrous dysplasia, and 3 cases of unclassified spindle cell tumor). Results: Among the 30 patients with POS, 15 were male and 15 were female, ranging in age from 10 to 59 years (mean 35 years, median 30.5 years). Among the 14 patients with LGCOS, four were male and 10 were female, ranging in age from 15 to 56 years (mean 37 years, median 36 years). All except one case were successfully detected by FISH. MDM2 gene amplification was detected in 27 cases of POS (27/29,91.3%) and 8 cases of LGCOS (8/14). All the negative controls were negative for MDM2 gene amplification. The positive rate of MDM2 gene amplification was significantly different between the case group and the control group (P<0.05). The sensitivity and specificity of MDM2 gene amplification in diagnosing POS and LGCOS were 91.3% and 100.0%; and 57.1% and 100.0%, respectively. The sensitivity and specificity of MDM2 gene amplification in diagnosing LGOS (including POS and LGCOS) were 81.3% and 100.0%, respectively. In cases where MDM2 gene was amplified, the MDM2 amplified signal was clustered. Nine cases showed increased CEP12 signal different from polyploidy which was displayed as small and weak signal points or cloud flocculent and cluster signals. Conclusions: Detection of MDM2 gene amplification by FISH is a highly sensitive and specific marker for LGOS. The interpretation criteria for FISH detection of MDM2 amplification are currently not unified. The signal characteristics need more attention when interpreting.
目的： 探讨应用荧光原位杂交（FISH）检测MDM2扩增辅助诊断低级别骨肉瘤（low-grade osteosarcoma，LGOS）的价值及判读标准。 方法： 收集北京积水潭医院病理科2009年4月1日至2022年8月10日应用FISH检测MDM2扩增辅助诊断骨肉瘤的病例，以骨旁骨肉瘤（parosteal osteosarcoma，POS）30例、低级别中心性骨肉瘤（low-grade central osteosarcoma，LGCOS）14例为病例组，以其他骨病变58例（包括纤维结构不良28例，骨巨细胞瘤5例，普通型骨肉瘤4例，骨膜骨肉瘤2例，骨折后修复性改变2例，多形性未分化肉瘤2例，低度恶性肌纤维母细胞肉瘤2例，纤维结构不良恶变2例，平滑肌肉瘤1例，硬化性上皮样纤维肉瘤1例，恶性外周神经鞘瘤1例，骨的促结缔组织增生性纤维瘤1例，孤立性纤维性肿瘤1例，动脉瘤样骨囊肿1例，透明细胞软骨肉瘤1例，骨性纤维结构不良1例，梭形细胞肿瘤未分类3例）为对照组，分析应用FISH检测MDM2扩增对于辅助诊断LGOS的价值并结合文献探讨判读标准。 结果： 组织学诊断为POS的病例30例，男性15例，女性15例；年龄10~59岁，平均年龄35岁，中位年龄30.5岁。除1例检测失败外，27例（27/29，91.3%）FISH检测MDM2扩增结果为阳性。组织学诊断为LGCOS的病例14例，男性4例，女性10例；年龄15~56岁，平均年龄37岁，中位年龄36岁。8例（8/14）FISH检测MDM2扩增结果为阳性。对照组58例，FISH检测MDM2扩增结果均为阴性。MDM2扩增率在POS组、LGCOS组与对照组相比差异均有统计学意义（均P<0.05）。FISH检测MDM2扩增诊断POS的灵敏度和特异度分别为93.1%和100.0%，诊断LGCOS的灵敏度和特异度分别为57.1%和100.0%，诊断LGOS（POS与LGCOS）的灵敏度和特异度为81.3%和100.0%。在MDM2扩增阳性病例中，MDM2扩增信号均呈簇状。9例（9/35，25.7%；6例POS和3例LGCOS）可见不同于多倍体的CEP12信号增多，表现为增加的小的、微弱的信号点或呈云絮状、团簇状的信号。 结论： FISH检测MDM2扩增对LGOS有较高的诊断价值，FISH检测MDM2扩增的判读标准目前尚不统一，结果判断时要关注信号特点，部分病例中可见CEP12信号增多。.