Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Liver Transpl. 2011 Aug;17(8):943-54. doi: 10.1002/lt.22314.
We investigated the phenotype of hepatocellular carcinoma (HCC) in livers removed during transplantation after local ablation therapy by transarterial chemoembolization (TACE). This study involved 80 HCC nodules (40 treated with TACE and 40 not treated with local ablation before transplantation) observed in 64 explanted livers and included clinicopathological evaluations as well as single and double immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK19), epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), and CD133. HCCs with complete necrosis post-TACE without viable tumors were excluded from the analysis. Cholangiolar, glandular, or spindle cell areas suggestive of a mixed hepatocholangiocellular phenotype were seen in 14 post-TACE HCCs and in none of the non-TACE HCCs (P < 0.001). According to single-epitope immunohistochemistry of post-TACE HCCs, CD133, CK19, EpCAM, and NCAM were expressed in 14 (35%), 8 (20%), 12 (30%), and 8 (20%), respectively. Only EpCAM was detected in 4 non-TACE HCC cases (10%). RT-PCR experiments using tissues obtained by laser microdissection showed that 4 of 5 investigated post-TACE HCCs expressed at least 1 of the markers, which were coexpressed in 3 of 5 tumors, whereas CD133 and EpCAM were individually expressed in 2 non-TACE HCCs. Double immunostaining showed that CD133(+) cells frequently coexpressed CK19, EpCAM, or NCAM. Interestingly, the recurrence rate for patients with CD133(+) post-TACE HCC was significantly higher than the rate for patients with CD133(-) post-TACE HCC (P = 0.025). In conclusion, HCC with the combined hepatocholangiocellular phenotype appears to be more frequent in post-TACE HCC versus untreated HCC. Further studies are needed to investigate the potential relationships between TACE and HCC subpopulations with a chemoembolization-resistant phenotype and their clinical significance.
我们研究了经肝动脉化疗栓塞（TACE）局部消融治疗后移植肝脏中肝细胞癌（HCC）的表型。本研究纳入了 64 例肝移植中观察到的 80 个 HCC 结节（40 个接受 TACE 治疗，40 个未接受局部消融治疗），包括临床病理评估以及细胞角蛋白 19（CK19）、上皮细胞黏附分子（EpCAM）、神经细胞黏附分子（NCAM）和 CD133 的单免疫组化、双免疫组化和逆转录聚合酶链反应（RT-PCR）。排除 TACE 后完全坏死且无存活肿瘤的 HCC。TACE 后 HCC 中有 14 例出现胆管、腺或梭形细胞区域，提示混合性肝胆细胞表型，而非 TACE HCC 中无一例出现（P < 0.001）。根据 TACE 后 HCC 的单表位免疫组化，CD133、CK19、EpCAM 和 NCAM 的表达分别为 14 例（35%）、8 例（20%）、12 例（30%）和 8 例（20%）。而非 TACE HCC 中仅检测到 4 例（10%）表达 EpCAM。使用激光微切割获得的组织进行 RT-PCR 实验显示，5 例 TACE 后 HCC 中有 4 例至少表达 1 种标志物，其中 3 例肿瘤共表达 3 种标志物，而非 TACE HCC 中有 2 例单独表达 CD133 和 EpCAM。双免疫组化显示 CD133(+)细胞常共表达 CK19、EpCAM 或 NCAM。有趣的是，CD133(+) TACE 后 HCC 患者的复发率明显高于 CD133(-) TACE 后 HCC 患者（P = 0.025）。总之，与未经治疗的 HCC 相比，TACE 后 HCC 中出现具有混合性肝胆细胞表型的 HCC 更为常见。需要进一步研究以探讨 TACE 与具有化疗栓塞耐药表型的 HCC 亚群之间的潜在关系及其临床意义。
