摘要
目的研究细胞角蛋白19（CK19）在低血清甲胎蛋白（AFP）浓度乙型肝炎病毒（HBV）相关肝细胞癌（HCC）组织中的表达与肿瘤增殖、R0切除术后复发和预后的关系。方法应用组织芯片技术和免疫组织化学PV-6000两步法检测235例HBV相关HCC组织中CK19和Ki67蛋白的表达，应用逆转录聚合酶链反应检测20例HBV相关HCC组织中CK19mRNA的表达，分析低血清AFP浓度下CK19与Ki67表达的关系，及其与HCC患者R0术后复发和预后的关系。结果本组235例HBV相关HCC患者中，R0切除术后血清AFP〈400斗g／L组和AFP≥400μg／L组患者的中位无病生存时间（DFS）分别为31．2个月和13．8个月（P=0．041），总生存时间（OS）分别为84．0个月和58．6个月（P：0．125）；1年内肿瘤复发者分别为44例（27．5％）和37例（49．3％，P=0．001）。CK19蛋白阳性表达组的中位DFS（11．6个月）与阴性表达组（27．0个月）比较，差异无统计学意义（P〉0．05）；阳性表达组患者的0s低于阴性表达组，差异有统计学意义（P=0．023）。AFP〈400斗g／L组的CK19阳性表达患者的DFS和OS均低于阴性表达患者，差异均有统计学意义（均P〈0．05）。CK19的表达与组织分化程度、多发病灶、血管癌栓、区域淋巴结转移和1年术后复发有关（均P〈0．05）。在AFP〈400μg／L组肿瘤组织中，CK19阳性表达组的术后1年复发率（53．0％）高于阴性表达组（23．0％，P〈0．001），CK19阳性表达组的中位DFS（11．3个月）低于阴性表达组（34．0个月，P=0．010）。CK19表达组中位OS为19．5个月，低于阴性表达组（84．0个月，P=0．001）。Cox回归分析显示，CK19阳性表达是HCC早期复发和预后的独立影响因素。结论在AFP〈400μg／L的HBV相关HCC患者中，HCC组织中CK19阳性表达者其肿瘤增殖和侵袭性强，是早期复发和不良预后的重要指标。
Objective To investigate the expression of CK19 in HBV-related hepatocellular carcinoma （HCC） tissues in patients with low serum AFP concentration and the relationship between them and the recurrence and prognosis of HCC after R0 radical hepatectomy. Methods The expressions of CK19 and Ki67 in HCC tissues of 235 cases were examined using tissue microarray and two-step methods of PV- 6000 immunohistochemistry. The expression of CK19 mRNA in 20 frozen HCC specimens was examined by RT-PCR. The correlation between gene expressions and tumor recurrence and prognosis was analyzed. Results Among the 235 HBV-related HCC patients after R0 radical hepatectomy, the median disease-free survival （DFS） was 31.2 months in the patients with serum AFP 〈 400 μg/L and 13.8 months in the patients with serum AFP ≥400 μg/L （P = 0. 041 ）, the overall survival （OS） was 84.0 and 58.6 months in the two subgroups （P =0. 125）, and the tumor recurrence within one year was in 43 cases （27%） and 37 cases （49.3%）, respectively, （P =0. 001 ）. The DFS was 11.6 months in the CK19-positive cases and 27.0 months in the CK19-negative cases （P 〉 0.05 ）. The OS was significantly lower in the CK19-positive cases than that in the CK19-negative cases （P = 0.023）. Both DFS and OS in the CK19-positive cases with AFP 〈 400 μg/L were significantly lower than those in the CK19-negative cases with AFP 〈 400 μg/L （bothP 〈 0.05 ）. The CK19 expression was significantly correlated with histological differentiation （ P = 0. 023 ）, number of tumor foci （ P = 0.044）, vascular tumor embolism （ P = 0. 005 ）, regional lymph node metastasis （ P = 0.023 ）, and 1-year recurrence （ P = 0. 006 ）. Among the patients with AFP 〈 400 μg/L, the 1-year recurrence was 53% in the CK19-positive cases and 23% in the CK19-negative cases （P 〈 0. 001 ）, the median DFS was 11.3 months in CK19-positive cases and 34.0 months in CK19-negative cases （P = 0.010）, and the median OS was 19.5 months in the CK19-positive cases, significantly lower than 84.0 months in the CK19-negative cases （ P = 0. 001 ）. Cox regression analysis showed that CK19-positive expression was an independent factor affecting early HCC recurrence and prognosis. Conclusion In HBV- related HCC patients after radical hepatectomy with AFP 〈 400 μg/L, positive expression of CK19 indicates a higher proliferation and invasiveness of HCC, and is an important factor of early recurrence and poor prognosis.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2012年第10期753-758,共6页
Chinese Journal of Oncology
关键词
癌
肝细胞
肝炎
乙型
慢性
甲胎蛋白类
CK19
KI67
复发
预后
Carcinoma, hepatocellular
Hepatitis B, chronic
Alpha-fetoproteins
CK19
Ki67
Recurrence
Prognosis
