Rhee Hyungjin, An Chansik, Kim Hye-Young, Yoo Jeong Eun, Park Young Nyun, Kim Myeong-Jin
Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Pathology, Brain Korea 21 PLUS Project for Medical Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Republic of Korea.
Liver Cancer. 2019 Feb;8(1):24-40. doi: 10.1159/000488540. Epub 2018 May 15.
The purpose of our study was to examine the histopathologic characteristics of hepatocellular carcinoma (HCC) with irregular rim-like arterial phase enhancement (IRE), which has been reported to be associated with more aggressive tumor behavior.
We investigated 84 pathologically confirmed HCCs in 84 patients who underwent curative hepatic resection after gadoxetate-enhanced magnetic resonance imaging between January 2008 and February 2013. Two abdominal radiologists independently reviewed these images and classified HCCs into two categories: HCC showing IRE (IRE-HCC) and HCC showing hypoenhancement or diffuse arterial enhancement (non-IRE-HCC). Twenty-two HCCs were classified as IRE-HCCs, and 51 were classified as non-IRE-HCCs concordantly by both reviewers. The remaining 11 HCCs, on whose radiologic classifications the reviewers disagreed, were classified as HCCs with intermediate enhancement patterns. The HCC clinicopathologic characteristics and patient outcomes were then compared.
IRE-HCCs showed more frequent microvascular invasion (91 vs. 35%), lower microvascular density (246.5 vs. 426.5/mm), higher proportions of sinusoid-like microvascular pattern (55 vs. 0%) and macrotrabecular pattern (45 vs. 0%), and larger areas of tumor necrosis (15 vs. 0%) and fibrous stroma (8.3 vs. 2.1%) than non-IRE-HCCs. IRE-HCCs also expressed higher levels of immunomarkers of hypoxia (carbonic anhydrase IX, 64 vs. 8%) and stemness (EpCAM, 50 vs. 20%). values were < 0.001 for all comparisons except for EpCAM ( = 0.026). HCCs with intermediate enhancement patterns showed mixed/intermediate pathologic features from both IRE- and non-IRE-HCCs. IRE-HCC patients showed poorer 5-year disease-free survival after curative resection than non-IRE-HCC patients ( = 0.005).
IRE-HCCs demonstrate aggressive histopathologic features, including more hypoxic and fibrotic tumor microenvironments and increased stemness, compared to non-IRE-HCCs. IRE might therefore serve as a noninvasive imaging biomarker for aggressive HCC.
我们研究的目的是检查具有不规则边缘样动脉期强化（IRE）的肝细胞癌（HCC）的组织病理学特征，据报道这种强化与更具侵袭性的肿瘤行为相关。
我们调查了2008年1月至2013年2月间84例接受钆塞酸二钠增强磁共振成像后行根治性肝切除术的患者的84例经病理证实的HCC。两名腹部放射科医生独立审查这些图像，并将HCC分为两类：显示IRE的HCC（IRE-HCC）和显示低增强或弥漫性动脉期增强的HCC（非IRE-HCC）。22例HCC被分类为IRE-HCC，51例被两名审查者一致分类为非IRE-HCC。其余11例HCC，审查者对其放射学分类存在分歧，被分类为具有中间增强模式的HCC。然后比较HCC的临床病理特征和患者预后。
与非IRE-HCC相比，IRE-HCC显示出更频繁的微血管侵犯（91%对35%）、更低的微血管密度（246.5对426.5/mm）、更高比例的窦状微血管模式（55%对0%）和大小梁模式（45%对0%），以及更大面积的肿瘤坏死（15%对0%）和纤维间质（8.3%对2.1%）。IRE-HCC还表达更高水平的缺氧免疫标志物（碳酸酐酶IX，64%对8%）和干性标志物（EpCAM，50%对20%）。除EpCAM外（P = 0.026），所有比较的P值均<0.001。具有中间增强模式的HCC显示出来自IRE-HCC和非IRE-HCC的混合/中间病理特征。IRE-HCC患者根治性切除术后的5年无病生存率低于非IRE-HCC患者（P = 0.005）。
与非IRE-HCC相比，IRE-HCC表现出侵袭性的组织病理学特征包，括更多缺氧和纤维化的肿瘤微环境以及干性增加。因此，IRE可能作为侵袭性HCC的一种非侵入性成像生物标志物。
