SALL4 Expression in Hepatocellular Carcinomas Is Associated with EpCAM-Positivity and a Poor Prognosis.
BACKGROUND
There is increasing interest in hepatocellular carcinomas (HCC) expressing "stemness"-related markers, as they have been associated with aggressive behavior and poor prognosis. In this study, we investigated the usefulness of Sal-like protein 4 (SALL4), a recently proposed candidate marker of "stemness."


METHODS
Immunohistochemical stains were performed for SALL4, K19, and epithelial cellular adhesion molecule (EpCAM) on tissue microarrays constructed from 190 surgically resected HCCs, and the results were correlated with the clinicopathological features and patient survival data.


RESULTS
Nuclear SALL4 expression was observed in 39/190 HCCs (20.5%), while K19 and EpCAM were expressed in 30 (15.9%) and 92 (48.7%) HCCs, respectively. The nuclear expression was generally weak, punctate or clumped. SALL4 expression was significantly associated with a poor overall survival compared to SALL4-negative HCCs (p = .014) compared to SALL4-negative HCCs. On multivariate analysis adjusted for tumor size, multiplicity, vascular invasion, and pathological tumor stage, SALL4 remained as a significant independent predictor of decreased overall survival (p= .004). SALL4 expression was positively correlated with EpCAM expression (p = .013) but not with K19 expression. HCCs that expressed both SALL4 and EpCAM were associated with significantly decreased overall survival, compared to those cases which were negative for both of these markers (p = .031).


CONCLUSIONS
Although SALL4 expression was not significantly correlated with other clinicopathological parameters suggestive of tumor aggressiveness, SALL4 expression was an independent predictor of poor overall survival in human HCCs, and was also positively correlated with EpCAM expression.
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.
Hyunjin
H
Park
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.
Hyejung
H
Lee
Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Korea.
An Na
AN
Seo
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.
Jai Young
JY
Cho
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.
Young Rok
YR
Choi
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.
Yoo-Seok
YS
Yoon
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.
Ho-Seong
HS
Han
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Young Nyun
YN
Park
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.
Haeryoung
H
Kim
Carcinoma, hepatocellular; Immunohistochemistry; Prognosis; SALL4