Immunohistochemical molecular analysis indicates hepatocellular carcinoma subgroups that reflect tumor aggressiveness

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Abstract

Summary 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.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalHuman Pathology
Volume50
DOIs
Publication statusPublished - 2016 Apr 1

Fingerprint

Catenins
Hepatocellular Carcinoma
Stem Cells
Neoplasms
Portal Vein
Neoplasm Metastasis
Keratin-19
Glutamate-Ammonia Ligase
Mitosis
Immunohistochemistry
Cell Proliferation
Recurrence

Keywords

  • Aggressiveness
  • Biliary/stem cell marker
  • Hepatocellular carcinoma
  • Immunohistochemistry
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{1322cc46c7024914815110beee9d43f7,
title = "Immunohistochemical molecular analysis indicates hepatocellular carcinoma subgroups that reflect tumor aggressiveness",
abstract = "Summary 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.",
keywords = "Aggressiveness, Biliary/stem cell marker, Hepatocellular carcinoma, Immunohistochemistry, Wnt/β-catenin signaling",
author = "Hanako Tsujikawa and Yohei Masugi and Ken Yamazaki and Osamu Itano and Yuukou Kitagawa and Michiie Sakamoto",
year = "2016",
month = "4",
day = "1",
doi = "10.1016/j.humpath.2015.10.014",
language = "English",
volume = "50",
pages = "24--33",
journal = "Human Pathology",
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T1 - Immunohistochemical molecular analysis indicates hepatocellular carcinoma subgroups that reflect tumor aggressiveness

AU - Tsujikawa, Hanako

AU - Masugi, Yohei

AU - Yamazaki, Ken

AU - Itano, Osamu

AU - Kitagawa, Yuukou

AU - Sakamoto, Michiie

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Summary 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.

AB - Summary 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.

KW - Aggressiveness

KW - Biliary/stem cell marker

KW - Hepatocellular carcinoma

KW - Immunohistochemistry

KW - Wnt/β-catenin signaling

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DO - 10.1016/j.humpath.2015.10.014

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