摘要
【摘要】目的探讨多结节肝细胞癌的肿瘤克隆起源方式与肝移植术后肝癌复发的相关性。方法选取2005年8月至2010年8月经肝移植治疗的符合美国加州大学旧金山分校（UCSF）标准的多结节型肝细胞癌患者60例，采用纤维切割技术，获取肝癌组织后提取基因组DNA。SSCP-PCR法检测12个高频肝细胞癌微卫星杂合性缺失（LOH）的发生状态，判定肿瘤克隆起源方式为单中心肝内转移型（intrahepatic metastasis，IM型）、多中心发生型（multicentric occurrence，MO型）及复合型（IM＋MO型）。分析各型克隆起源方式与患者无瘤存活率、肿瘤病理学特征及血清AFP水平之间的相关性。结果60例多结节肝细胞癌患者中，45例有2个肿瘤结节，占多结节肝细胞癌患者的75％（45／60），15例有3个肿瘤结节者，占25％（／60）；剔除2例不能判定肿瘤克隆起源分型病例，共58例纳人分析，其中IM型组、MO型组和IM＋MO型组，分别占34．48oA（20／58）、56．90％（33／58）和8．62％（5／58）；三组患者的3年累积无瘤存活率分别为50．00％、78．79％和40％，微血管侵犯（Micro Vascular Invasion，MVI）发生率为100％、18．18％和100％，肿瘤低分化率（Ⅲ级～Ⅳ级）为80％、51．52％和80％，血清AFP浓度为231．25μg／L（2．78~9736．27μ／L）、24．59μg／L（1．16~2674．50μg／L）和122．58μg／L（16．20～1608．03μg／L）。结论MO型肝细胞癌患者肝移植术后3年无瘤存活率明显高于IM型和IM＋MO型，考虑与其镜下癌栓发生率低，病理分化程度高、术前AFP低等密切相关。肿瘤克隆起源方式可能作为多结节HCC的病期评判要素及预测肝移植术后肿瘤复发风险的重要参考指标。
Objective To investigate the correlation between the clonal origin of hepatocellular carcinoma （HCC） and the recurrence of pluri-nodular HCC after liver transplantation. Methods Sixty pluri-nodular HCC patients, conformed to the UCSF＇s standard, were selected and given liver transplantation. Then tumor nodules were separated from the normal tissue by microdissection. The state of 12 HCC high frequency microsatellite loss of heterozygosity （LOH） was detected by SSCP- PCR, and the tumor clone origin for intrahepatic metastasis （IM）, multicentric occurrence （MO） and 1M ＋ MO type was determined. The correlation between different types of clonal origin and the three- year tumor-flee survival rate, tumor pathological features and the level of serum AFP was analyzed. Results Forty-five cases had two nodules of HCC, and the rest 15 cases had three nodules. After excluding two cases whom the clonal origin pattern was not identified, the remaining 58 cases were enrolled in the study. The IM group, MO group and IM ＋ MO group were set up, accounting for 34. 48% （20/58）, 56. 90% （33/58） and 8. 62%（5/58） respectively. In IM group, MO group and IM ＋ MO group, the three-year tumor-free survival rate was 50. 00%, 78.79% and 40%; the incidence of MVI was 100%, 18. 18% and 100%; the low differentiation rate of tumor was 80%, 51.52% and 80%; and the mean eoncentrations of AFP were 231.25 （2. 78-9736. 27）, 24. 59 （1.16-2674. 50） and 122. 58μg/L （16. 20-1608. 03μg/L） respectively. Conclusion The three-year tumor-free survival rate of MO was significantly higher than that of IM and IM ＋ MO types, which was closely related to the low incidence of tumor thrombi, the high degree of pathological differentiation and low preoperative AFP. Tumor clonal origin may serve as an important reference index for the evaluation of the disease stage of multiple nodules HCC and prediet the risk of tumor recurrence after liver transplantation.
出处
《中华器官移植杂志》
CAS
CSCD
2016年第10期592-600,共9页
Chinese Journal of Organ Transplantation
基金
基金项目：器官移植科国家临床重点专科建设项目（2013544）
天津市卫生行业重点攻关项目（13KG103）
天津市器官移植临床医学研究中心项目
关键词
多结节肝细胞癌
克隆起源
微卫星杂合性缺失
肝移植
病理
肿瘤复发
pluri-nodular hepatocellular carcinoma
clonal origin
loss of heterozygosity
liver transplantation
pathology
tumor recurrence
