Hypoxia after transarterial chemoembolization may trigger a progenitor cell phenotype in hepatocellular carcinoma
Hypoxia after transarterial chemoembolization may trigger a progenitor cell phenotype in hepatocellular carcinoma
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DOI：
10.1111/his.12623
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发表时间：
2015-10-01
期刊：
影响因子：
6.4
通讯作者：
Guindi, Maha
中科院分区：
文献类型：
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作者：
Lai, Jin-Ping;Conley, Andrew;Guindi, Maha
目的：为了检验缺氧标志物碳酸酐酶IX（CAIX）和胆管细胞/祖细胞标志物细胞角蛋白（CK）19和上皮细胞粘附分子（EpCAM）可能在肝细胞癌（HCC）经动脉化疗栓塞（TACE）后的缺氧区域中表达的假设。在57例HCC中进行了CAIX、CK 19和EpCAM（BerEP 4）的免疫组化，包括40例TACE治疗部位附近的残留/复发肿瘤和来自相同40例患者的17例未经治疗的肿瘤。CAIX在40例残留/复发的HCC中有19例表达，在17例未治疗的HCC中有2例表达。治疗组CAIX免疫反应阳性率显著高于未治疗组（47.5%对11.8%，P = 0.015）。CK 19和EpCAM分别在19例CAIX阳性TACE治疗的HCC中的6例和19例CAIX阳性TACE治疗的HCC中的7例中表达，但在CAIX阴性肿瘤或未治疗的肿瘤中不表达。CK 19和CAIX免疫反应性之间以及EpCAM和CAIX免疫反应性之间存在显著关联（分别为P = 0.007和P = 0.003）。CAIX和CK 19的双重染色显示两种蛋白在6例中的5例中共定位。7例EpCAM阳性的肿瘤中有3例CK 19阳性。结论：缺氧可能触发与胆管细胞/祖细胞分化相关的蛋白质表达，提示TACE矛盾地导致侵袭性肿瘤表型。
Aims: To test the hypothesis that the hypoxia marker carbonic anhydrase IX (CAIX), and the cholangiocytic/progenitor markers cytokeratin (CK) 19 and epithelial cell adhesion molecule (EpCAM), may be expressed in areas of hypoxia in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE).Methods and results: Immunohistochemistry for CAIX, CK19 and EpCAM (BerEP4) was performed in 57 HCCs, including 40 residual/recurrent tumours adjacent to the TACE treatment site and 17 untreated tumours from the same 40 patients. CAIX was exxpressed in 19 of 40 residual/recurrent HCCs and in two of 17 untreated HCCs. The rate of CAIX immunoreactivity in the treated tumours was significantly higher than that in the nontreated tumours (47.5% versus 11.8%, P = 0.015). CK19 and EpCAM were expressed in six of 19 and in seven of 19 CAIX-positive TACE-treated HCCs, respectively, but were not expressed in CAIX-negative tumours or untreated tumours. There were significant associations between CK19 and CAIX immunoreactivity, and between EpCAM and CAIX immunoreactivity (P = 0.007 and P = 0.003, respectively). Double staining of CAIX and CK19 showed co-localization of both proteins in five of six cases. Three of seven EpCAM-positive tumours were also positive for CK19.Conclusions: Hypoxia may trigger the expression of proteins that are normally associated with cholangiocytic/progenitor cell differentiation, suggesting that TACE paradoxically causes an aggressive tumour phenotype.