Immunohistochemical molecular analysis indicates hepatocellular carcinoma subgroups that reflect tumor aggressiveness

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• 作者：Hanako Tsujikawa ; MD^a ; Yohei Masugi ; MD ; PhD^a ; Ken Yamazaki ; PhD^a ; Osamu Itano ; MD ; PhD^b ; Yuko Kitagawa ; MD ; PhD^b ; Michiie Sakamoto ; MD ; PhD^a ; ^{msakamot@z5.keio.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hepatocellular carcinoma ; Immunohistochemistry ; Aggressiveness ; Biliary/stem cell marker ; Wnt/β-catenin signaling
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：50
• 期：Complete
• 页码：24-33
• 全文大小：1027 K

文摘

Histopathologic parameters and molecular markers are widely accepted as useful predictors of tumor aggressiveness in hepatocellular carcinoma (HCC). However, few studies have analyzed immunohistochemical profiles comprehensively in one series, a fact that has resulted in fragmentation of information that could be applied in clinical practice. We conducted immunohistochemical expression analysis of biliary/stem cell markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule, and CD133), Wnt/β-catenin signaling–related molecules (β-catenin and glutamine synthetase), p53, and cell proliferation markers (Ki-67 and mitosis) in 162 HCCs surgically resected from 142 patients and analyzed the results with respect to clinicopathological features. Immunohistochemical analysis broadly identified 3 groups: the biliary/stem cell marker–positive group, the Wnt/β-catenin signaling–related marker–positive group, and the biliary/stem cell marker–negative and Wnt/β-catenin signaling–related marker–negative group. p53 was frequently positive in the biliary/stem cell marker–positive group, but it was rarely positive in the Wnt/β-catenin signaling–related marker–positive group. The biliary/stem cell marker–positive group exhibited poor tumor differentiation, increased frequency of portal vein invasion and/or intrahepatic metastasis, and highly proliferative activity. In contrast, the biliary/stem cell marker–negative and Wnt/β-catenin signaling–related marker–negative group exhibited better tumor differentiation, a decreased frequency of portal vein invasion and/or intrahepatic metastasis, and less proliferative activity. The Wnt/β-catenin signaling–related marker–positive group showed neither tendency. The biliary/stem cell marker–positive group had the shortest time to recurrence among the 3 groups. Immunohistochemical profiling of HCC reflects tumor aggressiveness and suggests the potential efficacy of immunohistochemistry-based subclassification of HCC.