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目的:肝母细胞瘤(hepatoblastoma,HB)是罕见的肝脏恶性肿瘤,其生物学特性在不同患者中表现不同。本研究通过对HB的临床病理特点及基因组微卫星变异特征的分析,探讨其在评估HB生物学特性中的意义。方法:选取第二军医大学东方肝胆外科医院1983-01-01-2013-12-31收治的<18岁且经手术切除的HB患者50例。分析50例患者的临床、生化参数和病理参数,采用显微切割法分离并提取33例HB组织和配对周边肝组织的DNA,采用PCR-SSCP方法,检测10个微卫星的变异特点,统计分析各参数之间的相关性。结果:50例HB患者,男性患者较女性的分期更差,P=0.015;TNM为Ⅲ/Ⅳ期的患者血清AFP≥1 000μg/L的比例(92.9%)显著高于Ⅱ期患者(59.1%),P=0.004;有瘤栓形成患者的血清AFP≥1 000μg/L的比例(100.0%)显著高于无瘤栓患者(70.3%),P=0.026;单纯胎儿型HB血清AFP<1 000μg/L的比例(33.3%)显著高于其他类型(8.7%),P=0.036;有卫星灶的HB同时有瘤栓形成的比例(61.5%)显著高于无卫星灶(13.5%),P=0.001;上皮间叶混合型HB直径≥10cm的比例(100.0%)明显高于其他类型(50.0%),P=0.009。HB发生11p15.5附近微卫星变异的频率为60.6%(20/33),其中14例(70.0%)HB呈肝表面外生性生长,明显高于未发生微卫星变异(30.1%),P=0.038。TNM分期为Ⅱ/Ⅲ级的HB中,微卫星杂合性缺失率(54.4%)明显低于Ⅳ期(100.0%),P=0.013。结论:患者男性、TNM分期Ⅲ/Ⅳ级、瘤栓形成、微卫星变异、外生生长和血清AFP≥1 000μg/L等可能是导致HB恶性生物学行为的主要因素。
OBJECTIVE: Hepatoblastoma (HB) is a rare malignant liver tumor with different biological characteristics in different patients. In this study, we analyzed the clinicopathological characteristics of HB and the microsatellite polymorphism of the genomic DNA to explore its significance in the assessment of the biological characteristics of HB. Methods: 50 cases of <18 years old and surgically resected HB patients admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University from January 1983 to January 2013 were enrolled. The clinical, biochemical parameters and pathological parameters of 50 patients were analyzed. DNA of 33 cases of HB and matched liver tissues were isolated and extracted by microdissection. The variation characteristics of 10 microsatellites were detected by PCR-SSCP. Statistical analysis The correlation between the parameters. Results: The staging of male patients was worse than that of women in 50 cases of HB (P = 0.015). The proportion of serum AFP≥1 000μg / L (92.9%) in patients with stage Ⅲ / Ⅳ TNM was significantly higher than that in stage Ⅱ patients (59.1% ), P = 0.004. The percentage of serum AFP≥1 000 μg / L (100.0%) in patients with tumor thrombus was significantly higher than that in patients without tumor thrombus (70.3%), P = 0.026. / L (33.3%) was significantly higher than that of other types (8.7%), P = 0.036. The proportion of HBs with satellite lesions (61.5%) was significantly higher than that without satellite = 0.001; the proportion of epithelial mixed HBs ≥10cm (100.0%) was significantly higher than other types (50.0%), P = 0.009. The frequencies of HBsAg mutation in the vicinity of 11p15.5 were 60.6% (20/33), of which 14 cases (70.0%) had exogenous growth on the liver surface, which was significantly higher than that in the absence of microsatellite mutation (30.1%), P = 0.038. In HB with TNM stage Ⅱ / Ⅲ, the loss rate of microsatellite heterozygosity (54.4%) was significantly lower than that of stage Ⅳ (100.0%), P = 0.013. Conclusion: Male patients with TNM stage Ⅲ / Ⅳ grade, tumor thrombus formation, microsatellite mutation, exogenous growth and serum AFP≥1 000 μg / L may be the main factors leading to malignant biological behavior of.