title: ALDH1A1-overexpressing cells are differentiated cells but not cancer stem or progenitor cells in human hepatocellular carcinoma.
abstract: Aldehyde dehydrogenase 1A1 (ALDH1A1) is considered to be a cancer stem cell marker in several human malignancies. However, the role of ALDH1A1 in hepatocellular carcinoma (HCC) has not been well elucidated. In this study, we investigated the relationship between ALDH1A1 and clinicopathological findings and examined whether ALDH1A1 deserves to be a cancer stem cell marker in HCC. Sixty HCC samples obtained from surgical resection were collected for immunohistochemical (IHC) staining. Of these 60 samples, 47 samples of HCC tumorous and non-tumorous tissues were evaluated with qRT-PCR. There was no significant difference in the ALDH1A1-mRNA level between tumorous and non-tumorous tissues. Tumorous ALDH1A1-mRNA level had no relationship with the clinicopathological features. Immunoreactivity of ALDH1A1 was classified into two groups based on the percentage of ALDH1A1-overexpressing cells. The ALDH1A1-high group was significantly associated with low serum levels of α-fetoprotein, small tumor diameter, very little lymphovascular invasion, more differentiated pathology and good stage. The ALDH1A1-high group showed more favorable prognosis for recurrence-free survival. In double-staining IHC, ALDH1A1 was not co-expressed with BMI1, EpCAM, CD13, CD24, CD90 and CD133, which reported as cancer stem cell markers in HCC. In conclusion, ALDH1A1-overexpressing cells could appear to be differentiated cells rather than cancer stem cells in HCC.
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.|Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hisamatsu
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakashima
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hatano
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Multidisciplinary Therapy for Hepato-Biliary-Pancreatic Cancer, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Osada
authors.affiliation: Division of Pathology, Gifu Municipal Hospital, Gifu, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Pathology, Gifu University Hospital, Gifu, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000032:analysis* / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D018572:Disease-Free Survival; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology; D010641:Phenotype; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050697:Retinal Dehydrogenase; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: ALDH1A1; Pathology Section; cancer stem cell marker; hepatocellular carcinoma; prognosis