肝细胞癌8号染色体微卫星变异及其与临床病理特征的关系

目的　探讨肝细胞癌 (HCC)微卫星变异的特点及其与临床病理表现的相关性。方法采用毛细管电泳DNA分析系统 ,对 5 6例HCC中 8号染色体上 10个微卫星的杂合子丢失 (LOH)、微卫星不稳定性 (MSI)和等位基因失衡 (AI) 3种变异特征进行检测。结果　 5 6例HCC在 8号染色体上 10个基因位点发生LOH的总频率为 6 6 1% (37/ 5 6 ) ,LOH以D8S2 6 1最高为 5 3 5 % (2 3/ 4 3) ,其次为D8S172 1(5 2 5 % )和D8S1771(5 2 5 % )。D8S2 77基因位点 ,血清HBsAg阳性患者的LOH频率显著高于HBsAg阴性者 (P <0 0 1) ,D8S2 6 1、D8S2 98和D8S1733基因位点 ,血清HBsAg阴性患者的LOH频率显著高于HBsAg阳性者 (P <0 0 1) ;D8S2 98和D8S1771基因位点 ,直径 >3cm肿瘤的LOH率明显高于≤ 3cm组 (P <0 0 5和P <0 0 1) ;在D8S172 1基因位点 ,无包膜或包膜不完整的肿瘤的LOH显著高于包膜完整的肿瘤 (P <0 0 1) ;D8S2 98和D8S1771基因位点 ,肝内转移者的LOH明显高于无肝内转移者 (P <0 0 5 )。MSI的频率为 12 5 % (7/ 5 6 ) ,AI的频率为 19 6 % (11/ 5 6 )。结论HCC在 8号染色体上存在广泛的微卫星变异 ,其中LOH方式在HCC的发生和发展过程中起重要作用 ,MSI的作用次之。特定基因位点的LOH与临床和病理学参数有一定的相关性

Relationship between microsatellite alterations on chromosome 8 and clinicopathological characteristics in hepatocellular carcinoma

Objective To study the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC). Methods Ten high-polymorphic microsatellite markers on chromosome 8 were selected to detect the loss of heterozygosity (LOH), microsatellite instability (MSI) and allelic imbalance (AI) in 56 HCCs using automatic capillary array electrophoresis DNA analysis system. Results LOH was found in 37 of 56 HCCs (66.1%) on at least 10 locus. The three most frequently altered loci were D8S261(53.5%,23/43), D8S1721(52.5%,21/40) and D8S1771(52.5%,21/40). LOH on D8S277 was significantly higher in cases with positive serum HBsAg than in those with negative HBsAg (P<0.01). Similarly, LOH on D8S261, D8S298 and D8S1733 occurred more frequently in patients with negative HBsAg than those with positive HBsAg (P<0.01). LOH on D8S298 and D8S1771 were more frequent in tumors larger than 3 cm in size (P<0.05 and P<0.01 respectively). LOH frequencies of D8S1721 were significantly higher in cases with absent or partially encapsulated tumor than in those with intact tumor capsule (P<0.05). LOH on D8S298 and D8S1771 were more frequently detected in tumors with intrahepatic metastasis than those without (P<0.01). MSI was found in 12.5%(7/56)cases. AI was found in 19.6%(11/56) of all cases examined. Conclusions(Microsatellite alterations) on chromosome 8 were frequent in HCC. LOH, possibly representing alterations of the tumor suppressor pathway, may play an important role in hepatocarcinogenesis. MSI, reflecting a dysfunction of the mismatch repair pathway, may also contribute to this process, but in a less significant way. LOH at some particular loci is associated with certain clinicopathological parameters of human HCC.