ALDH1A1-overexpressing cells are differentiated cells but not cancer stem or progenitor cells in human hepatocellular carcinoma

// Kaori Tanaka 1, 2 , Hiroyuki Tomita 1 , Kenji Hisamatsu 1 , Takayuki Nakashima 1 , Yuichiro Hatano 1 , Yoshiyuki Sasaki 2 , Shinji Osada 3 , Takuji Tanaka 4 , Tatsuhiko Miyazaki 5 , Kazuhiro Yoshida 2 , Akira Hara 1 1 Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan 2 Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan 3 Department of Multidisciplinary Therapy for Hepato-Biliary-Pancreatic Cancer, Gifu University Graduate School of Medicine, Gifu, Japan 4 Division of Pathology, Gifu Municipal Hospital, Gifu, Japan 5 Division of Pathology, Gifu University Hospital, Gifu, Japan Correspondence to: Hiroyuki Tomita, e-mail: h_tomita@gifu-u.ac.jp Keywords: ALDH1A1, hepatocellular carcinoma, prognosis, cancer stem cell marker Received: May 28, 2015      Accepted: June 08, 2015      Published: June 22, 2015 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.