title: Clinicopathologic characteristics of SALL4-immunopositive hepatocellular carcinoma.
abstract: The aim of this study was to investigate the clinicopathologic characteristics of sal-like protein 4 (SALL4)-immunopositive hepatocellular carcinoma (HCC). Solitary HCCs that were surgically treated at the University of Tokyo Hospital between 2000 and 2008 were the subject of this study. Diffuse, non-punctate nuclear immunoreactivity to SALL4 was observed in 47 of 337 HCCs (13.9%). Compared to patients with SALL4-negative HCC, patients with SALL4-positive HCC were younger (mean 59.2 years vs. 65.2 years), more frequently female (44.7% vs. 18.3%) and positive for hepatitis B virus angigen (42.6% vs. 18.6%). They had much higher serum levels of alpha-fetoprotein (median 3976.5 ng/ml vs. 14.0 ng/ml) (P < 0.001). Liver function tended to be favourable, as was shown by less indocyanine green retention at 15 minutes (ICG15), in patients with SALL4-positive HCCs (P < 0.001). Histologically, SALL4-positive HCCs exhibited less histological differentiation (P < 0.001) and had a higher frequency of micro- or macrovascular invasion (72.3% vs. 54.1%, P = 0.019) and intrahepatic metastasis (34.0% vs. 19.3%, P = 0.022) than SALL4-negative HCCs. SALL4-positive HCCs were more frequently immunoreactive for cytokeratin 19 (42.6% vs. 11.7%, P < 0.001) and EpCAM (51.1% vs. 8.3%, P < 0.001). The log-rank test indicated short-term disease-free survival (< 1 year) of patients with SALL4-positive HCC was worse than those with SALL4-negative HCC (P = 0.019). Multivariate analyses, however, failed to show the prognostic significance of SALL4 immunoreactivity in HCCs. In conclusion, SALL4-immunopositive HCCs constitute a subset with characteristic patient backgrounds and somewhat aggressive behavior, as was manifested by frequent vascular invasion and intrahepatic metastasis. There was little prognostic significance of SALL4 immunoreactivity in HCCs.
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Shibahara
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan.
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Ando
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Hepato-Biliary-Pancreatic Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Hepato-Biliary-Pancreatic Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hesegawa
authors.affiliation: Hepato-Biliary-Pancreatic Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
keywords: Alpha-fetoprotein; Cytokeratin 19; EpCAM; Hepatocellular carcinoma; Progenitor cell; SALL4