Abstract Human epidermal growth factor receptors (HER) play a critical role in the branching morpho- genesis of renal tubules. In the current study, we ana- lyzed the expression of HER2 in Wilms tumor and assessed the role of this gene in the tumorgenesis of Wilms tumor. During the period from 1960 to 2005, 40 patients with Wilms tumor were treated in our department. Twenty-four of those patients (except those with clear cell sarcoma of the kidney and malignant rhabdoid tumor of the kidney) were col- lected and assessed. The histological component of each Wilms tumor was divided into three categories (epithelial, blastemal, and mesenchymal) and the ex- tent of HER2 protein expression was analyzed immu- nohistochemically. The normal kidney tissue accompanied with 12 cases of Wilms tumor was also examined. In the normal kidney, HER2 showed a strong immunoreactivity in the cell membranes of the collecting tubules and in the endothelial cells. Of 24 cases, 15 cases showed an epithelial component, while 24 cases had a blastemal component and 21 cases had a mesenchymal component, respectively. Among the 15 specimens with epithelial cell differentiation, eight (53.3%) showed HER2 immunoreactive epithelial cells. HER2 immunoreactive blastemal cells were present in 11 (45.8%) of 24 specimens with blastemal cells. On the other hand, only 3 (14.3%) of 21 speci- mens containing mesenchymal cells showed HER2 immunoreactivity. These results suggest that the extent of HER2 expression is associated with epithelial dif- ferentiation in Wilms tumor. These histological find- ings may therefore help to explain the development of Wilms tumor from the standpoint of histological dif- ferentiation. Keywords Wilms tumor Æ HER2 Æ Epithelial Æ Blastemal Æ Mesenchymal Introduction Wilms tumor is a pediatric malignancy and one of the most common solid tumors occurring in children [1]. The biologic behavior is difficult to predict on the basis of histopathologic findings alone [2]. Human epidermal growth factor receptor 2 (HER2), which is encoded by the c-erb-B2 gene, is a trans- membrane glycoprotein belonging to a family of four receptors for tyrosine kinases that mediate cellular proliferation, differentiation, and survival through the binding of growth factor ligands [3–6]. HER2 was originally isolated from an ethylnitrosourea-induced rodent neuroblastoma [7] and it has subsequently been identified in other human malignant solid tumors [8– 10]. Both in vitro and in vivo studies have demon- strated the gene amplification or protein overexpres- sion of HER2 to induce tumorigenesis, to increase the metastatic potential, and to promote chemoresistance [11, 12]. The dysregulation of these receptors is linked M. Salem Æ Y. Kinoshita (&) Æ T. Tajiri Æ R. Souzaki Æ K. Tatsuta Æ M. Higashi Æ T. Izaki Æ T. Taguchi Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan e-mail: kinoppy@pedsurg.med.kyushu-u.ac.jp K. Kohashi Æ M. Tsuneyoshi Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Pediatr Surg Int (2006) 22:891–896 DOI 10.1007/s00383-006-1762-0 123 ORIGINAL ARTICLE Association between the HER2 expression and histological differentiation in Wilms tumor M. Salem Æ Y. Kinoshita Æ T. Tajiri Æ R. Souzaki Æ K. Tatsuta Æ M. Higashi Æ T. Izaki Æ K. Kohashi Æ M. Tsuneyoshi Æ T. Taguchi Published online: 25 August 2006 Ó Springer-Verlag 2006