PAX2 Expression in Wilms Tumors and Other Childhood Neoplasms

Abstract

PAX2 plays an important role in kidney development; although small studies have demonstrated PAX2 expression in Wilms tumors (WT), comprehensive studies on formalin-fixed tissue are lacking. Thus, we systematically evaluated PAX2 immunohistochemical staining in a retrospective study of pediatric WT, as compared with other pediatric tumors. We stained formalin-fixed, paraffin-embedded sections from 39 WT, 6 nephrogenic rests, 8 non-Wilms renal tumors, and 43 nonrenal pediatric small round cell tumors with 2 different PAX2 polyclonal antibodies. PAX2 demonstrated strong, diffuse staining of epithelial and blastema components of WT (97% of cases). PAX2 stained WT stroma in fewer cases (23%), but 80% of anaplastic foci were positive. Nephrogenic rests, 1 case of metanephric adenoma, and 1 pediatric renal cell carcinoma were also PAX2 positive; other pediatric renal tumors were negative. Neuroblastoma, primitive neuroectodermal tumor/Ewings, and T-cell acute lymphoblastic lymphoma (ALL) were PAX2 negative. However, PAX2 weakly stained some cases of B-cell ALL rhabdomyosarcoma (RMS) was also stained, especially alveolar RMS (83%), with less staining of embryonal RMS (13%). One of the antibodies also stained maturing myoid cytoplasm of WT and RMS. This study shows that PAX2 is a sensitive marker of WT (sensitivity 97%), but PAX2 shows weak-to-moderate-intensity nuclear staining of RMS and B-cell ALL, somewhat limiting its utility. However, PAX2 may be a helpful marker in certain diagnostic situations. We speculate that RMS and B-cell ALL staining could be due to antibody cross-reactivity with PAX family members with known expression in RMS and B-cell ALL.

Expression pattern of PAX2 in hyperplastic and malignant endometrium

“…Alterations in PAX2 have been associated with various renal congenital anomalies and disorders [5][6][7]. Furthermore, aberrantly over-expression of PAX2 has been described in renal tumors including Wilms' tumor [8], nephrogenic adenomas [9], and renal cell carcinomas [10]. More recently, PAX2 has been suggested as a potential therapeutic target gene in renal cancers [11].…”

Graded levels of Pax2a and Pax8 regulate cell differentiation during sensory placode formation

“…Humans with PAX2 haploinsufficiencies exhibit renal hypoplasia, vesicoureteric reflux and optic nerve coloboma (Alur et al, 2010;Schimmenti, 2011), whereas persistent expression of PAX2 causes a variety of cystic and dysplastic renal diseases (Cunliffe et al, 1998;Davis et al, 2011). This implies that levels of this transcriptional regulator must be strictly controlled (Eccles et al, 2002).…”

PAX2 in human kidney malformations and disease

“…Specifically, PAX2 over-expression has been documented in human Wilms tumors [4,7,69] and in adult renal carcinoma [70]. Additionally, experiments in mice utilizing a cytomegalovirus vector to constitutively overexpress PAX2 demonstrated that PAX2 could promote oncogenesis both in vitro and in vivo [71].…”