相邻肝硬化组织中的血管生成和增殖标志物可预测肝移植后肝细胞癌的预后。

Angiogenesis and proliferation markers in adjacent cirrhotic tissue could predict hepatocellular carcinoma outcome after liver transplantation.

作者信息

Campillo Ana, Solanas Estela, Morandeira Maria J, Castiella Tomas, Lorente Sara, Garcia-Gil Francisco Agustín, Piazuelo Elena, de Martino Alba, Serrano Maria T

机构信息

Departments of aGastroenterology and Hepatology bHistopathology cSurgery, University Hospital Lozano Blesa dIIS Aragon, Aragon Institute of Health Sciences eMedical University of Zaragoza, Zaragoza fNetworked Biomedical Research Center Hepatic and Digestive Diseases (CIBERehd), Spain.

出版信息

Eur J Gastroenterol Hepatol. 2014 Aug;26(8):871-9. doi: 10.1097/MEG.0000000000000131.

DOI:10.1097/MEG.0000000000000131

PMID:24922356

Abstract

INTRODUCTION

The current staging systems for hepatocellular carcinoma (HCC) do not sufficiently predict outcomes after liver transplantation (LT). The present study assessed whether some tissue markers related to proliferation and angiogenesis have prognostic value.

PATIENTS AND METHODS

The expression of CD34, vascular endothelial growth factor (VEGF), VEGFR2, VEGFR1, angiopoietin-1, angiopoietin-2, TIE2, COX-2, and proliferating cell nuclear antigen (PCNA) in tumor and adjacent cirrhotic tissue samples from 36 patients with HCC (n=10 with tumor recurrence after LT) was determined by immunochemistry. Microvessel density was assessed by CD34 staining and the PCNA labeling index calculated as the percentage of positive cells among at least 1000 hepatocyte nuclei studied in each sample using the computer program ContimUZ. VEGF, VEGFR2, VEGFR-1, angiopoietin-1, angiopoietin-2, TIE2, and COX-2 staining were evaluated by two blinded pathologists. The tumor recurrence rate was analyzed after a minimum follow-up of 36 months.

RESULTS

A higher proliferation index in both tumor and adjacent cirrhotic tissue was related to HCC recurrence. The proliferation index in tumor tissue was also related to microvascular invasion. High expression (staining in ≥50% of hepatocytes) of COX2 [P=0.025, odds ratio (OR)=7.5, 95% confidence interval (CI) 1.3-43.4], VEGF (P=0.01, OR=12, 95% CI 1.8-80.4), and its receptor VEGFR-2 (P=0.02, OR=8.5, 95% CI 1.4-49.5) in cirrhotic liver tissue, but not tumor tissue, was related to HCC recurrence after LT.

CONCLUSION

A high proliferation index in tumor and cirrhotic tissue and high expression levels of some angiogenic markers in adjacent cirrhotic tissue could be predictive of tumor recurrence after LT.

摘要

引言

目前肝细胞癌（HCC）的分期系统对肝移植（LT）后的预后预测不够充分。本研究评估了一些与增殖和血管生成相关的组织标志物是否具有预后价值。

患者与方法

通过免疫化学方法测定36例HCC患者（n = 10例LT后肿瘤复发）的肿瘤及相邻肝硬化组织样本中CD34、血管内皮生长因子（VEGF）、VEGFR2、VEGFR1、血管生成素-1、血管生成素-2、TIE2、COX-2和增殖细胞核抗原（PCNA）的表达。通过CD34染色评估微血管密度，并使用计算机程序ContimUZ计算PCNA标记指数，即每个样本中至少1000个肝细胞核中阳性细胞的百分比。VEGF、VEGFR2、VEGFR-1、血管生成素-1、血管生成素-2、TIE2和COX-2染色由两名盲法病理学家评估。在至少随访36个月后分析肿瘤复发率。

结果

肿瘤及相邻肝硬化组织中较高的增殖指数与HCC复发相关。肿瘤组织中的增殖指数也与微血管侵犯有关。肝硬化肝组织中COX2（P = 0.025，优势比[OR] = 7.5，95%置信区间[CI] 1.3 - 43.4）、VEGF（P = 0.01，OR = 12，95% CI 1.8 - 80.4）及其受体VEGFR-2（P = 0.02，OR = 8.5，95% CI 1.4 - 49.5）的高表达（≥50%肝细胞染色）与LT后HCC复发相关，但肿瘤组织中无关。