癌旁肝组织中缺氧诱导因子2α预测原发性肝细胞肝癌切除术后复发预后的价值

High expression of hypoxia inducible factor 2α in peritumoral liver tissue is associated with early recurrence and poor survival after curative resection of hepatocellular carcinoma

目的探讨肝癌以及癌旁肝组织中缺氧诱导因子2α(HIF-2α)预测原发性肝癌切除术后复发和预后的价值。方法从1999年至2006年我所968例原发性肝癌患者中随机选取105例制成组织芯片,随访至2010年3月。采用免疫组织化学方法染色并半定量分析肝癌以及相应的癌旁组织中HIF-2α的表达,分析HIF-2α高低组主要临床相关资料的差异,并评价其与患者复发、预后的相关性。结果肝癌中HIF-2α表达高低和预后无显著相关性。肝癌癌旁肝组织中HIF-2α阴性患者57例,1,3,5年生存率(92.7%,74.5%,58.6%)、无瘤生存率(80.1%,58.6%,44.6%)和早期复发(19例)显著好于癌旁HIF-2α阳性患者(46例)的总体生存率(75.4%,50.3%,41.0%)、无瘤生存率(55.1%,35.3%,22.9%)和早期复发(25例)。两组患者的临床病理特征的差异无统计学意义。多因素结果提示癌旁HIF-2α高表达为术后总体生存和无瘤生存的独立预后因素。结论 HIF-2α可有效预测原发性肝癌切除术后患者的复发和预后。

Objective To investigate the prognostic values of the intratumoral and peritumoral expression of hypoxia inducible factor 2α （HIF-2α） in hepatocellular carcinoma （HCC） patients after curative resection. Methods Immunohistochemistry was used to detect the expression of HIF-2α in intratumoral and peritumoral tissues from 105 patients receiving hepatectomy for histologically proven HCC at our hospital from 1999--2006. All patients were observed until March 2010. The prognostic value of HIF-2α and other cilinicopathological factors were analyzed by the application of Kaplan-Meier method and multivariate Cox proportional hazards model. Results Intratumoral HIF-2α was not associated with overall survival （OS） and time to progression （TTP）. Low peritumoral HIF-2α expression, with few early recurrence, had higher 1,3,5-year OS （92.7 %, 74.5 %, 58.6 %） and TTP （80.1% ,58. 6% ,44. 6%） rates compared with OS （75.4%,50.3%,41.0%,P =0.003） and TTP （55.1%,35.3%,22.9%,P=0.011） high group （P=0.003,P=0.011, respectively） ,and was an independent prognostic factor for both OS （P = 0. 001） and TTP （P = 0. 029）. Conclusions High peritumoral HIF-2α was associated with HCC early recurrence, TTP and OS, highlighting the importance of peritumoral microenvironment in the recurrence and metastasis of HCC.