Service d'Anatomie pathologique, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, AP-HP, 93143 Bondy, France; Université Paris 13, Sorbonne Paris Cité, UFR SMBH, F-93000 Bobigny, France.
J Hepatol. 2013 Dec;59(6):1264-70. doi: 10.1016/j.jhep.2013.07.030. Epub 2013 Aug 6.
BACKGROUND & AIMS: The prognosis of hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA) is mainly linked to tumor recurrence. So far, no tissue biomarker of recurrence has been validated in biopsy samples. We aimed at investigating the prognostic value of tissue biomarkers in HCC biopsy samples of patients treated with RFA.
All consecutive naive patients from 3 university hospitals, with compensated cirrhosis, early-stage (BCLC 0/A) uninodular HCC treated with RFA, and available tumor biopsy, were included. Edmondson's grade, and the expression of cytokeratin 19, glutamine synthase, beta-catenin, epithelial cell adhesion molecule (EpCAM), and endothelial cell-specific molecule 1 (ESM-1) were assessed. Main clinical end points were overall and early recurrence. Statistical analyses were performed using Kaplan Meier, Log-rank test, and Cox models.
150 patients were included. Recurrence, death or liver transplantation occurred in 85, 51, and 12 patients, respectively. Median follow-up was 27months. ESM-1 expression by HCC stromal endothelial cells was observed in 58 patients (40%) and was associated with higher serum AFP levels, larger tumor, and more frequent expression of EpCAM and surrogate markers of activation of the Wnt-ß-catenin pathway. The 2 independent predictive factors of overall recurrence were serum AFP (HR 1.11 [1.002; 1.22], p=0.045) and ESM-1 expression (HR 1.56 [1.004; 2.43], p=0.048). ESM-1 expression was also an independent predictive factor of early recurrence (HR 1.81 [1.02; 3.21], p=0.042).
ESM-1 expression by stromal endothelial cells, in tumor biopsy samples, has an independent predictive value of early recurrence after RFA.
射频消融（RFA）治疗肝细胞癌（HCC）的预后主要与肿瘤复发相关。迄今为止，尚未在活检样本中验证与复发相关的组织生物标志物。本研究旨在探讨 HCC 患者 RFA 治疗后活检样本中组织生物标志物的预后价值。
纳入来自 3 所大学医院的连续初治患者，代偿性肝硬化，早期（BCLC 0/A）单发结节 HCC 行 RFA 治疗，且有肿瘤活检标本。评估了 Edmondson 分级，以及细胞角蛋白 19、谷氨酰胺合成酶、β-连环蛋白、上皮细胞黏附分子（EpCAM）和内皮细胞特异性分子 1（ESM-1）的表达。主要临床终点为总体和早期复发。采用 Kaplan-Meier、Log-rank 检验和 Cox 模型进行统计分析。
共纳入 150 例患者。85、51 和 12 例患者分别出现复发、死亡或肝移植。中位随访时间为 27 个月。58 例（40%）患者的 HCC 基质内皮细胞表达 ESM-1，其与较高的血清 AFP 水平、较大的肿瘤以及 EpCAM 和 Wnt-β-连环蛋白通路激活的替代标志物的更频繁表达相关。总体复发的 2 个独立预测因素为血清 AFP（HR 1.11 [1.002；1.22]，p=0.045）和 ESM-1 表达（HR 1.56 [1.004；2.43]，p=0.048）。ESM-1 表达也是早期复发的独立预测因素（HR 1.81 [1.02；3.21]，p=0.042）。
肿瘤活检样本中基质内皮细胞表达 ESM-1 对 RFA 后早期复发有独立的预测价值。
