Research Papers: Pathology:

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

Kaori Tanaka _, Hiroyuki Tomita, Kenji Hisamatsu, Noriyuki Nakashima, Yuichiro Hatano, Yoshiyuki Sasaki, Shinji Osada, Takuji Tanaka, Tatsuhiko Miyazaki, Kazuhiro Yoshida and Akira Hara

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Oncotarget. 2015; 6:24722-24732. https://doi.org/10.18632/oncotarget.4406

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Kaori Tanaka1,2, Hiroyuki Tomita1, Kenji Hisamatsu1, Takayuki Nakashima1, Yuichiro Hatano1, Yoshiyuki Sasaki2, Shinji Osada3, Takuji Tanaka4, Tatsuhiko Miyazaki5, Kazuhiro Yoshida2, Akira Hara1

1Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan

2Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan

3Department of Multidisciplinary Therapy for Hepato-Biliary-Pancreatic Cancer, Gifu University Graduate School of Medicine, Gifu, Japan

4Division of Pathology, Gifu Municipal Hospital, Gifu, Japan

5Division of Pathology, Gifu University Hospital, Gifu, Japan

Correspondence to:

Hiroyuki Tomita, e-mail: [email protected]

Keywords: ALDH1A1, hepatocellular carcinoma, prognosis, cancer stem cell marker

Received: May 28, 2015     Accepted: June 08, 2015     Published: June 22, 2015


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.

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