GATA3 differential expression in neuroblastoma and nephroblastoma

Abstract

We have read with great interest the report by Wiles et al, published in Cancer Cytopathology, about the immunohistochemical expression of the GATA3 antibody in cytological material from neuroblastomas.1 They evaluated GATA3 immunohistochemical expression in neuroblastoma cytology and/or biopsy samples, and diffuse nuclear positivity was found in all 30 specimens studied. Each sample revealed either strong (n = 26) or moderate nuclear staining (n = 4) in more than 75% of neuroblastoma cells, regardless of the presence or lack of stromata, necrosis, or differentiation. GATA3 is a relatively recent marker useful for diagnosing tumors of various epithelial and nonepithelial origins such as mammary tumors, urothelial tumors, renal tumors, germ cell tumors, mesotheliomas, and paragangliomas. Moreover, it is usually negative in round cell sarcomas.2 In contrast, little is known about GATA3 expression in blastemal or other small round cell pediatric tumors. Nonaka et al3 reported the presence of diffuse GATA3 expression in the neuroblastoma family of tumors and a lack of expression in other small round cell tumors. The distinction between neuroblastomas and nephroblastomas may be delicate because the clinical and radiological presentation may be overlapping. Moreover, we have previously encountered important difficulties in the cytological differential diagnosis between poorly differentiated neuroblastomas without neuropils or differentiating cells from blastema-rich monophasic nephroblastomas.4 We initiated this study to evaluate GATA3's immunohistochemical utility in the cytological differential diagnosis between neuroblastomas and nephroblastomas. Six cell blocks from the most recent consecutive ultrasound-guided fine-needle aspirates from neuroblastomas and 6 cell blocks from nephroblastomas were investigated. Paraffin-embedded sections were stained with the GATA3 antibody (clone L50-823; Biocare, Concord, California). Immunostaining was scored as negative, weakly positive, or strongly positive. The percentage of positive cells was also estimated. Nuclear staining was found in all 6 cases of neuroblastoma but in only 1 case of nephroblastoma. No cytoplasmic staining was observed. The intensity varied from weak (4 cases) to strong (2 cases; Figs. 1 and 2). The percentage of positive cells varied from 5% to 100%. Only 1 of the 6 cases of nephroblastoma showed weak nuclear positivity in 5% of tumor cells. The clinical data and the results of immunohistochemistry are presented in Table 1 On the basis of our results, we conclude that GATA3 may be a useful marker for differentiating neuroblastomas from nephroblastomas, especially when it is used with Phox2b and tyrosine-hydroxylase antibodies.3 Moreover, in some cases, GATA3 may be not specific, and positivity in a blastemal nephroblastoma may be a pitfall of a differential diagnosis with a poorly differentiated neuroblastoma. No specific funding was disclosed. The authors made no disclosures. Jerzy Klijanienko, MD, PhD, MIAC Martial Caly, PhD Paul Frénaux, MD Department of Pathology, Curie Institute, Paris, France Jan Klos, MD Department of Pathology, Stavanger University Hospital, Stavanger, Norway