title: Heterogeneity of The CD90+Population in Different Stages of Hepatocarcinogenesis.
abstract: We have characterized herein the heterogeneity of the CD90+population at each stage of hepatocarcinogenesis using a computer-assisted immunohistochemical staining evaluation method for quantitative analysis on tissue microarrays. We found that CD90 in Hepatocellular carcinoma (HCC) tissues, which has been shown to be a marker for cancer stem cells, is expressed on tumor cells, in the stroma or on endothelial cells. Sub-classification of the CD90+population was based on morphology and co-expression with known markers including CD45 and CD31. Multiple linear regression suggested that the percentage of CD90+cancer cells/hepatocyte (p<0.0001), level of overall CD90 expression (p<0.0014), and level of CD90 expression in tumor islands (p<0.0001) increased significantly in each stage of liver disease progression, while the level of stromal CD90 expression (p=0.1129) did not change significantly. Additionally, only the CD90+cancer cells were positive for other cancer stem cell (CSC) markers including CD24, CD44 and CD133 whereas the other CD90+cells were negative for these markers. CD90 expression in cirrhosis was observed in hepatocytes, the portal tract area and fibrous septa while CD90 expression in normal liver was limited only to the portal tract area. This study demonstrates the heterogeneity of the CD90+population in HCC where a small population of the CD90+ cells that expressed other CSC markers are CSCs and are associated with advanced stages of hepatocarcinogenesis. This heterogeneity should be emphasized in further studies where other methods may not be able to discriminate these distinct types of CD90+cells.
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States ; Department of Medicine, Faculty of Medicine Siriraj hospital, Mahidol University, Bangkok10700, Thailand.
authors.forename: Smathorn
authors.initials: S
authors.lastname: Thakolwiboon
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, United States.
authors.forename: Qixing
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States.
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Welling
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Lubman
keywords: CD90; Cancer stem cell; Hepatocarcinogenesis; Hepatocellular carcinoma; Immunohistochemistry; Thy-1