RESEARCH Immunoexpression of SALL4 in Wilms Tumors and Developing Kidney Jeremy Deisch & Jack Raisanen & Dinesh Rakheja Received: 5 November 2010 / Accepted: 6 January 2011 / Published online: 22 January 2011 # Arányi Lajos Foundation 2011 Abstract SALL4 is a zinc finger transcription factor that plays a role in the maintainence 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. Keywords Immunohistochemistry . Kidney development . Nephrogenic rest . SALL4 . Wilms tumor Introduction Wilms tumor is a primitive multilineage malignant neo- plasm of embryonic renal precursor cells that recapitulates renal embryogenesis and is often associated with and presumed to arise from persistent foci of embryonic renal tissue called nephrogenic rests. Since Wilms tumors have the potential for multilineage differentiation, it is likely that the Wilms tumor cells have a stem cell phenotype. Indeed, the presence of cells with stem cell phenotype may be responsible for resistance to chemo- and radiotherapy and post-therapy relapse in Wilms tumors [1]. SALL4 is a zinc finger transcription factor, which, along with Oct4, Pou5f1, and NanoG, plays a role in the maintainence and pluripotency of embryonic stem cells [2, 3]. Pertinently, SALL4 is important in renal development, and SALL4 mutations produce renal developmental abnormalities as a part of multiple congenital anomaly syndromes such as the DRRS (Duane-radial ray syndrome) and the IVIC (Instituto Venezolano de Investigaciones Científicas) syndrome. We hypothesized that SALL4 might be expressed by Wilms tumor cells. Therefore, we examined immunohistochemical staining for SALL4 in Wilms tumors, nephrogenic rests, and fetal kidneys. Materials and Methods Formalin-fixed and Paraffin-embedded Tissue This study was conducted with the approval of UT Southwestern Institutional Review Board. Immunohisto- chemistry for SALL4 was performed on tissue microarray sections of 52 Wilms tumor, 6 nephrogenic rests, and 13 fetal renal cortices spanning 15 to 39 weeks’ gestation. The Wilms tumor and fetal renal cortex tissue microarrays J. Deisch : J. Raisanen : D. Rakheja (*) Department of Pathology MC 9073, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA e-mail: dinesh.rakheja@utsouthwestern.edu D. Rakheja Children’s Medical Center, Dallas, TX, USA Pathol. Oncol. Res. (2011) 17:639–644 DOI 10.1007/s12253-011-9364-0