Immunoexpression of SALL4 in Wilms Tumors and Developing Kidney

Abstract

SALL4 is a zinc finger transcription factor that plays a role in the maintainance and pluripotency of embryonic stem cell and is important in renal development where SALL4 mutations give rise to renal malformations. Because Wilms tumor recapitulates renal embryogenesis, we hypothesized that Wilms tumor cells may also express SALL4. We performed immunohistochemistry for SALL4 on tissue microarray sections of Wilms tumors, nephrogenic rests, and fetal renal cortices. Half (26 out of 52) of the Wilms tumors showed SALL4 immunoreactivity, ranging from strong and diffuse to focal and weak. Blastemal, epithelial, and combined blastemal and epithelial patterns of immunoreactivity were identified. No cases showed stromal staining. In the fetal kidney, SALL4 expression was restricted to the blastema and primitive epithelium at 15 weeks' gestation. SALL4 staining was not seen at later gestational ages, in non-neoplastic postnatal kidneys, or in nephrogenic rests. Our study is the first to demonstrate SALL4 immunoreactivity in Wilms tumors and in developing fetal kidney. The absence of SALL4 staining in nephrogenic rests, the presumed precursors of Wilms tumors, is intriguing and suggests that Wilms tumors have a pluripotency quality that may be lacking in nephrogenic rests.

β-Catenin and K-RAS Synergize to Form Primitive Renal Epithelial Tumors with Features of Epithelial Wilms' Tumors

“…SALL4 is a recently described marker for the epithelial component of human WTs, and these tumors stained weakly positive for this by IHC staining ( Figure 3G). 53 Taken together, the expression pattern of these tumors reflects their epithelial dominance and suggests features that have been identified in some human WTs. Figure 4A).…”

Serum SALL4 Is a Novel Prognosis Biomarker with Tumor Recurrence and Poor Survival of Patients in Hepatocellular Carcinoma

“…In primary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), the expression of SALL4 is higher than health control. At the meaning time, some other kinds of tumor such as colorectal cancer, breast cancer, and Wilms tumors also express SALL4 [4, 7, 8]. More recently, SALL4 has been suggested as a marker of germ cell tumor, including primary and metastatic of yolk sac tumor [9–13].…”

Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex

“…11,12 After birth, SALL4 expression is down-regulated and absent in most adult tissues. However, SALL4 is expressed in various cancers, including a subset (30%) of solid tumors such as breast cancer, 13 ovarian cancer, 14 gastric cancer, 15 Wilms tumor, 16 and germ cell tumors, 14,[17][18][19][20][21] as well as in leukemias-most notably, almost all cases of human acute myeloid leukemia (AML) 22 and approximately 75% of B-cell acute lymphoblastic lymphoma/ leukemia. 23 We have also reported that SALL4 is enriched in the "side-population" of the leukemia and solid tumor cells.…”