ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma
ESM1 as a Marker of Macrotrabecular-Massive Hepatocellular Carcinoma
复制标题
DOI：
10.1158/1078-0432.ccr-19-0859
复制
发表时间：
2019-10-01
影响因子：
11.5
通讯作者：
Ziol, Marianne
中科院分区：
文献类型：
--
作者：
Calderaro, Julien;Meunier, Lea;Ziol, Marianne
目的：巨梁块状肝细胞癌（Macrotrabecular-massive hepatocellular carcinoma，MTM-HCC）是一种新的肝细胞癌形态学亚型，与切除或经皮消融术后早期复发相关，与经典的临床和放射学预后因素无关。本研究的目的是确定MTM-HCC的免疫组化标记物，以便于其诊断和实施到临床practice.Experimental设计：为了确定潜在的MTM-HCC的生物标志物，我们首先分析了基因表达谱数据从癌症基因组图谱研究，并进一步选择两个候选生物标志物。这两个生物标志物诊断MTM-HCC的性能进一步测试免疫组化在两个独立的系列67和132 HCC活检samples.Results：RNA测序数据分析表明，MTM-HCC的特点是高表达的新血管生成相关基因。选择了两种候选生物标志物，内皮特异性分子1（ESM 1）和碳酸酐酶IX（CAIX）。在发现系列中，基质内皮细胞表达ESM 1检测MTM-HCC的敏感性和特异性分别为97%（28/29）和92%（35/38）。CAIX的敏感性和特异性分别为48%（14/29）和89%（34/38）。在验证集中，ESM 1识别MTM-HCC的敏感性和特异性分别为93%（14/15）和91%（107/117）。两个系列中，观察者间对ESM 1评估的一致性良好（Cohen Kappa 0.77和0.76）。结论：使用分子驱动的生物标志物选择，我们确定ESM 1为MTM-HCC的可靠微环境免疫组化标志物。这些结果代表了肝癌形态分子分型在临床实践中的应用。
Purpose: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel morphological subtype of HCC associated with early relapse after resection or percutaneous ablation, independently of classical clinical and radiological prognostic factors. The aim of the present study was to identify immunohistochemical markers of MTM-HCC, to ease its diagnosis and implementation into clinical practice.Experimental Design: To identify potential biomarkers of MTM-HCC, we first analyzed gene expression profiling data from The Cancer Genome Atlas study and further selected two candidate biomarkers. Performance of both biomarkers for diagnosis of MTM-HCC was further tested by immunohistochemistry in two independent series of 67 and 132 HCC biopsy samples.Results: Analysis of RNA sequencing data showed that MTM-HCC was characterized by a high expression of neoangiogenesis-related genes. Two candidate biomarkers, Endothelial-Specific Molecule 1 (ESM1) and Carbonic Anhydrase IX (CAIX), were selected. In the discovery series, sensitivity and specificity of ESM1 expression by stromal endothelial cells for the detection of MTM-HCC were 97% (28/29), and 92% (35/38), respectively. Sensitivity and specificity of CAIX were 48% (14/29) and 89% (34/38). In the validation set, sensitivity and specificity of ESM1 for the identification of MTM-HCC were 93% (14/15) and 91% (107/117), respectively. Interobserver agreement for ESM1 assessment was good in both series (Cohen Kappa 0.77 and 0.76).Conclusions: Using a molecular-driven selection of biomarkers, we identified ESM1 as a reliable microenvironment immunohistochemical marker of MTM-HCC. The results represent a step toward the implementation of HCC morpho-molecular subtyping into clinical practice.