目的：探讨出血坏死表型的肝细胞癌（HN-HCC）的病理特征及临床预后。方法：前瞻性入组67 例手术与病理证实的HN-HCC 患者，并以同期37 例非HN-HCC（NHN-HCC）患者为对照。比较HN-HCC 与NHN-HCC 大体病理学差异；对HN-HCC 标本的组织病理学以及Ki-67、缺氧诱生因子1α（HIF-1α）、cleaved-caspase-3 的表达行多区域检测；检测HN-HCC 标本碳酸酐酶IX（CA-IX）和E- 钙黏蛋白的表达；比较HN-HCC 患者与NHN-HCC 患者术后生存率的差异。结果：HN-HCC 与NHN-HCC 呈现明显不同的大体病理形态。组织病理学观察与免疫组化检测显示，在HN-HCC 瘤内不同区域，细胞分化程度有明显差异；Ki-67、cleaved-caspase-3、HIF-1α 的表达量有明显差异（均P<0.05）。在HN-HCC 标本中，CA-IX 阳性表达率为86.5%（58/67），E- 钙黏蛋白为25.3%（17/67），且两者表达呈负相关（r=-2.601，P<0.05）。与NHN-HCC 患者比较，HN-HCC患者的1、3、5 年总体生存率（71.9%、10.7%、2.8% vs. 87.5%、35.6%、3.6%）与无瘤生存率（67.0%、15.4%、3.2% vs. 81.2%、34.3%、4.0%）均明显降低（均P<0.05）。结论：HCC 合并出血坏死病理改变提示肿瘤有较强的瘤内异质性和侵袭转移潜能，患者预后不良。
Pathologic features and prognosis of hepatocellular carcinoma with hemorrhagic/necrotic phenotype: a prospective preliminary study
Objective: To investigate the pathologic features and clinical outcomes of hepatocellular carcinoma (HCC) with hemorrhagic/necrotic phenotype (HN-HCC). Methods: Sixty-seven patients with HN-HCC that was confirmed by surgical findings and pathological examination were prospectively enrolled, and 37 HCC patients without hemorrhagic/necrotic phenotype (NHNHCC) treated during the same period served as control. The difference in gross pathology between HN-HCC and NHN-HCC was observed, histopathologic profiles and expressions of the Ki-67, hypoxia-inducible factor-1α (HIF-1α) and cleaved-caspase-3 were examined in multiple regions of the HN-HCC specimens, the expressions of carbonic anhydrase IX (CA-IX) and E-cadherin in the HN-HCC specimens were measured, and the difference in postoperative survival rate between HN-HCC and NHN-HCC patients was compared. Results: HN-HCC and NHN-HCC presented notably different gross appearance. Histopathologic examination and immunohistochemical staining showed that among different intratumoral regions of HN-HCC specimens, there were different degrees of cell differentiation and significantly different expression levels of Ki-67, cleavedcaspase- 3 and HIF-1α (all P<0.05). In HN-HCC specimens, the positive expression rate was 86.5% (58/67) for CA-IX and 25.3% (17/67) for E-cadherin, and there was a negative correlation between them (r=–2.601, P<0.05). In HN-HCC patients compared with NHN-HCC patients, both 1-, 3- and 5-year overall survival rate (71.9%, 10.7%, 2.8% vs. 87.5%, 35.6%, 3.6%) and tumor-free survival rate (67.0%, 15.4%, 3.2% vs. 81.2%, 34.3%, 4.0%) were significantly decreased (all P<0.05). Conclusion: Hemorrhagic/necrotic phenotype in HCC suggests that the tumor has strong intratumoral heterogeneity and metastasis potential, and the patients may face a poor prognosis.