期刊文献+

出血坏死表型肝细胞癌病理特征及预后的前瞻性初步研究 被引量:12

Pathologic features and prognosis of hepatocellular carcinoma with hemorrhagic/necrotic phenotype: a prospective preliminary study
原文传递
导出
摘要 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。 Objective: To investigate the pathologic features and clinical hemorrhagic/necrotic phenotype (HN-HCC). outcomes ofhepatocellular carcinoma (HCC) with 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 (NHN- HCC) 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-let (HIF-la) 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-lct (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.
出处 《中国普通外科杂志》 CAS CSCD 北大核心 2016年第1期6-11,共6页 China Journal of General Surgery
基金 国家自然科学基金面上资助项目(81372630 81372631) 湖南省发改委科研资助项目(湘发改高技[2013]1199) 湖南自然科学基金资助项目(12JJ3118) 中南大学湘雅医院2014年度临床科研基金资助项目(2014L07) "湘雅医院--北大末名临床与康复研究基金"资助项目(xywm2015126 xywm2015127)
关键词 肝细胞 出血 坏死 瘤内异质性 Carcinoma, Hepatocellular Hemorrhage Necrosis Intratumoral Heterogeneity
  • 相关文献

参考文献18

  • 1Friemel J,Rechsteiner M,Frick L,et al.Intratumor heterogeneity in hepatocellular carcinoma[J].Clin Cancer Res,2015,21(8):1951-1961.
  • 2Barcellos-Hoff MH,Lyden D,Wang TC.The evolution of the cancer niche during multistage carcinogenesis[J].Nat Rev Cancer,2013,13(7):511-518.
  • 3Bosman FT,Carneiro F,Hruban RH,et al.WHO classification of tumours of the digestive system [M].Lyon:IARC Press,2010,(3):1089.
  • 4Giannelli G,Rani B,Dituri F,et al.Moving towards personalised therapy in patients with hepatocellular carcinoma:the role of the microenvironment [J].Gut,2014,63(10):1668-1676.
  • 5无,丛文铭,步宏,陈杰,董辉,朱玉瑶,冯龙海,陈骏.原发性肝癌规范化病理诊断指南(2015版)[J].临床与实验病理学杂志,2015,31(3):241-246. 被引量:110
  • 6Huang WJ,Jeng YM,Lai HS,et al.Expression of hypoxic marker carbonic anhydrase IX predicts poor prognosis in resectable hepatocellular carcinoma [J].PLoS One,2015,10(3):e0119181.doi:10.1371/journal.pone.0119181.
  • 7Srivastava S,Thakkar B,Yeoh KG,et al.Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma [J].Virchows Arch,2015,466(5):541-548.
  • 8Mayer A,H?ckel M,Schlischewsky N,et al.Lacking hypoxia-mediated downregulation of E-cadherin in cancers of the uterine cervix [J].Br J Cancer,2013,108(2):402-408.
  • 9Tao YM,Huang JL,Zeng S,et al.BTB/POZ domain-containing protein 7:epithelial-mesenchymal transition promoter and prognostic biomarker of hepatocellular carcinoma[J].Hepatology,2013,57(6):2326-2337.
  • 10Bruix J,Gores GJ,Mazzaferro V.Hepatocellular carcinoma:clinical frontiers and perspectives [J].Gut,2014,63(5):844-855.

二级参考文献58

  • 1吴孟超.应重视小肝癌的诊断与治疗[J].中华医学杂志,2007,87(30):2089-2091. 被引量:11
  • 2Koh C, Zhao X, Samala N, et al. AASLD clinical practice guidelines: a critical review of scientific evidence and evolving recommendations[J]. Hepatology, 2013,58(6):2142-52.
  • 3William H, Ralph H, Timothy H, et al. Surgical pathology dissection: an illustrated guide[M]. New York:Springer, 2003:7-9.
  • 4Bass B P, Engel K B, Greytak S R, et al. A review of preanalytical factors affecting molecular, protein, and morphological analysis of formalin-fixed, paraffin-embedded(FFPE)tissue: how well do you know your FFPE specimen[J]? Arch Pathol Lab Med, 2014,138(11):1520-30.
  • 5Lu X Y, Xi T, Lau W Y, et al. Hepatocellular carcinoma expressing cholangiocyte phenotype is a novel subtype with highly aggressive behavior[J]. Ann Surg Oncol, 2011,18(8):2210-7.
  • 6Cai S W, Yang S Z, Gao J, et al. Prognostic significance of mast cell count following curative resection for pancreatic ductal adenocarcinoma[J]. Surgery, 2011,149(4):576-84.
  • 7应越英. 肝细胞肝癌的病理学[M]//汤钊猷.原发性肝癌. 上海:科学技术出版社, 1981:115-46.
  • 8Nakanuma Y, Curado M P, Franceschi S, et al. Intrahepatic cholangiocarcinoma[M]//Bosman F T, Carneiro F, Hruban R H, et al. WHO classification of tumours of the digestive system. 4 th ed. Lyon:IARC Press, 2010:217-27.
  • 9Cong W M, Wu M C. Small hepatocellular carcinoma: current and future approaches[J]. Hepatol Int, 2013,7(3):805-12.
  • 10Lu X Y, Xi T, Lau W Y, et al. Pathobiological features of small hepatocellular carcinoma: correlation between tumor size and biological behavior[J]. J Cancer Res Clin Oncol, 2011, 137(4):567-75.

共引文献117

同被引文献62

  • 1Anderson AR, Weaver AM, Cummings PT, et al. Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment[J]. Cell, 2006, 127(5):905-915.
  • 2Chaudhuri O, Koshy ST, Branco da Cunha C, et al. Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium[J]. Nat Mater, 2014, 13(10):970-978.
  • 3Unsal-Kacmaz K, Ragunathan S, Rosfjord E, et al. The interaction of PKN3 with RhoC promotes malignant growth[J]. Mol Oncol, 2012, 6(3):284-298.
  • 4Mukai H, Muramatsu A, Mashud R, et al. PKN3 is the major regulator of angiogenesis and tumor metastasis in mice[J]. Sci Rep, 2016, 6:18979.doi:10.1038/srep18979.
  • 5Zhang Y, Xu N, Xu J, et al. E2F1 is a novel fibrogenic gene that regulates cholestatic liver fibrosis through the Egr-1/SHP/EID1 network[J]. Hepatology, 2014, 60(3):919-930.
  • 6Tao Y, Hu K, Tan F, et al. SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway[J]. Oncotarget, 2016, 7(14):18356-18370.
  • 7Schrader J, Gordon-Walker TT, Aucott RL, et al. Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells[J]. Hepatology, 2011, 53(4):1192-1205.
  • 8Tao YM, Huang JL, Zeng S, et al. BTB/POZ domain-containing protein 7: epithelial-mesenchymal transition promoter and prognostic biomarker of hepatocellular carcinoma[J]. Hepatology, 2013, 57(6):2326-2337.
  • 9Leenders F, M?pert K, Schmiedeknecht A, et al. PKN3 is required for malignant prostate cell growth downstream of activated PI 3-kinase[J]. EMBO J, 2004, 23(16):3303-3313.
  • 10Ho DH, Lo RL, Chan LK, et al. Molecular pathogenesis of hepatocellular carcinoma[J]. Liver Cancer, 2016, 5(4):290-302.

引证文献12

二级引证文献74

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部