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.

MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression

“…In the present study, we also found that SALL4 was significantly upregulated in HCC tissues and cell lines, when compared to their matched adjacent normal tissues and normal liver cell line, respectively. Our data are consistent with those of previous studies (11,29,30). Moreover, in this study, to the best of our knowledge, we demonstrated for the first time that the overexpression of SALL4 reversed the suppressive effects of miR-33b overexpression on HCC cell proliferation, migration and invasion, indicating that SALL4 is involved in the miR-33b-meditated malignant phenotypes of HCC cells.…”

Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis

“…For the cancer recurrence, considering the available 4 studies [16, 23, 25, 28] and the 17 TCGA cohorts, a similar result was obtained confirming a worse prognostic role of SALL4+ (HR=1.52; 95% CI: 1.22-1.89, p=0.0002; I 2 =69%) (Figure 2b). …”

SALL4, the missing link between stem cells, development and cancer

“…These HCCs tend to be more aggressive and associated with a poor prognosis 68 . Compared to SALL4-negative cases, HCC patients with SALL4 expression show higher frequency of tumor cell invasion, intrahepatic metastasis, and are positive for cytokeratin 19 and Epithelial Cell Adhesion Molecule (EpCAM), as well as other cancer stem cell markers 112 . A positive correlation between SALL4 and EpCAM expression have been reported in other HCC studies 91113114115 .…”