Effendi Kathryn, Rahadiani Nur, Stephanie Marini, Kurebayashi Yutaka, Tsujikawa Hanako, Jasirwan Chyntia O M, Syaiful Ridho A, Sakamoto Michiie
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Department of Anatomical Pathology, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
J Clin Exp Hepatol. 2024 Nov-Dec;14(6):101451. doi: 10.1016/j.jceh.2024.101451. Epub 2024 May 23.
Standardized pathological evaluation based on immunohistochemical (IHC) analysis could improve hepatocellular carcinoma (HCC) diagnoses worldwide. We evaluated differences in clinicopathological subgroups in HCCs from two academic institutions in Tokyo-Japan, and Jakarta-Indonesia.
Clinicopathological parameters and molecular expression patterns were evaluated in 35 HCCs from Indonesia and 41 HCCs from Japan. IHC analysis of biliary/stem cell (B/S) markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule) and Wnt/β-catenin (W/B) signaling-related molecules (β-catenin, glutamine synthetase) could determine the IHC-based subgroups. For immuno-subtypes categorization, CD3/CD79α double immunohistochemistry was done to evaluate the infiltration of T and B cells. CD34 staining allowed identification of vessels that encapsulated tumor clusters (VETC).
Indonesian HCC patients were mostly <60 years old (66%) with a hepatitis B virus (HBV) background (82%), in contrast to Japanese HCC patients (8% and 19%, respectively, both < 0.001). In comparison with Japanese, Indonesian cases more frequently had >5 cm tumor size (74% vs 23%, = 0.001), poor differentiation (40% vs 24%), portal vein invasion (80% vs 61%), and α-fetoprotein levels >500 ng/ml (45% vs 13%, = 0.005). No significant differences were found in the proportions of B/S, W/B, and -/- subgroups from both countries. No immune-high tumors were observed among Indonesian cases, and immune-low tumors (66%) were more common than in Japanese cases (54%). VETC-positive tumors in Indonesia were significantly more common (29%), and most were in the HBV (90%) and -/- subgroups (90%), whereas Japanese VETC cases (10%, = 0.030) were nonviral (100%) and W/B subgroups (75%).
IHC-based analysis more precisely reflected the clinicopathological differences of HCCs in Japan and Indonesia. These findings provide new insights into standardization attempts and HCC heterogeneity among countries.
基于免疫组织化学（IHC）分析的标准化病理评估可改善全球肝细胞癌（HCC）的诊断。我们评估了来自日本东京和印度尼西亚雅加达的两个学术机构的HCC临床病理亚组的差异。
对来自印度尼西亚的35例HCC和来自日本的41例HCC的临床病理参数和分子表达模式进行评估。对胆管/干细胞（B/S）标志物（细胞角蛋白19、SALL4蛋白、上皮细胞粘附分子）和Wnt/β-连环蛋白（W/B）信号相关分子（β-连环蛋白、谷氨酰胺合成酶）进行IHC分析，可确定基于IHC的亚组。对于免疫亚型分类，进行CD3/CD79α双重免疫组织化学以评估T细胞和B细胞的浸润。CD34染色可识别包裹肿瘤簇的血管（VETC）。
印度尼西亚HCC患者大多年龄小于60岁（66%），有乙型肝炎病毒（HBV）感染背景（82%），而日本HCC患者分别为8%和19%（均P<0.001）。与日本患者相比，印度尼西亚患者肿瘤大小>5 cm更为常见（74%对23%，P = 0.001）、分化差（40%对24%）、门静脉侵犯（80%对61%）以及甲胎蛋白水平>500 ng/ml（45%对13%，P = 0.005）。两国B/S、W/B和-/-亚组的比例无显著差异。印度尼西亚病例中未观察到免疫高肿瘤，免疫低肿瘤（66%）比日本病例（54%）更常见。印度尼西亚VETC阳性肿瘤明显更常见（29%），且大多数在HBV（90%）和-/-亚组（90%）中，而日本VETC病例（10%，P = 0.030）为非病毒（100%）和W/B亚组（75%）。
基于IHC的分析更准确地反映了日本和印度尼西亚HCC的临床病理差异。这些发现为标准化尝试及各国HCC异质性提供了新见解。
