SALL4 Immunoreactivity Predicts Prognosis in Western Hepatocellular Carcinoma Patients but Is a Rare Event: A Study of 236 Cases
Open accessAbstract
Prognostic biomarkers that stratify patients with cancer are needed. Recent studies from Asia have implicated SALL4, a stem cell marker, as useful in identifying aggressive cases of hepatocellular carcinoma (HCC), and >50% of the cases tested had upregulation by microarray or dense immunoreactivity. Given the differences in predominant etiologic factors between the Asian and Western HCC, we sought to determine the prevalence of SALL4 immunoreactivity and its clinical relevance in Western HCC patients. We constructed tissue microarrays from 236 adult HCCs. Two cores each of tumor and nontumor tissue were included for each case. SALL4 immunohistochemistry was scored in a semiquantitative manner and the results correlated with recurrence-free and overall survival, in addition to standard demographics. Among the 236 cases, 165 (70.0%) were male. The median age was 59 years (range: 19 to 83 y). The majority (78.4%) of patients were white, followed by African American (15.7%), Asian (3.8%), Hispanic (1.7%), and Native American (0.4%). The majority of patients had hepatitis C (42.8%), followed by alcoholic liver disease and hepatitis B (both 8.9%), and nonalcoholic steatohepatitis (3.8%). SALL4 immunoreactivity was detected in a total of 3 cases (1.3%), and nonreactivity was validated on tissue sections from 73 cases. By univariate analysis, the SALL4-positive cases had significantly higher tumor grade (P=0.0251), more frequent lymphovascular invasion (P=0.0150), and shorter recurrence-free survival (7.90 vs. 57.54 mo; P=0.0115) and overall survival (7.90 vs. 64.87 mo; P=0.0018). Although SALL4 immunoreactivity in Western HCC is correlated with higher grade and poor prognosis, this is a rare event. Therefore, universal application of SALL4 as a biomarker for HCC should be performed with caution.
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SALL4 is overexpressed in many cancers with poor prognosis.
“SALL4 is overexpressed in many cancers with poor prognosis 61-67”
From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [63]
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- Authors
- Liu, T.-C., Vachharajani, N., Chapman, W. C., & Brunt, E. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Liu, Ta-Chiang
- Brunt, Elizabeth M.
- Venue
- American Journal of Surgical Pathology
- Published
- 2014-07
- Volume
- 38
- Issue
- 7
- Pages
- 966-972
- ISSN
- 0147-5185 (ISSN-L)
- PMC
- PMC5854193
- OpenAlex
- W2005224353
- Cited by
- 37
- References
- 52
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 5 · 2014: 2
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The American Journal of Surgical Pathology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020579)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- SALL4, hepatocellular carcinoma, prognostic factors, immunohistochemistry, recurrence-free survival, overall survival, tumor grade, lymphovascular invasion, Western patients, hepatitis C, stem cell markers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cell Differentiation, Female, Carcinoma, Hepatocellular, Humans, Immunohistochemistry, Liver Neoplasms, Male, Middle Aged, Missouri, Neoplasm Invasiveness, Predictive Value of Tests, Risk Factors, Time Factors, Transcription Factors, Biomarkers, Tumor, Reproducibility of Results, Treatment Outcome, Disease-Free Survival, Tissue Array Analysis, Kaplan-Meier Estimate, Young Adult, Neoplasm Grading
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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