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TTF-1 Expression in Nephroblastoma

Bisceglia, Michele MD*; Ragazzi, Moira MD† ‡; Galliani, Carlos A. MD§; Lastilla, Gaetano MD; Rosai, Juan MD

The American Journal of Surgical Pathology: March 2009 - Volume 33 - Issue 3 - p 454-461
doi: 10.1097/PAS.0b013e318185d21b
Original Articles

The unexpected observation of nuclear immunoreactivity for thyroid transcription factor-1 (TTF-1) associated with an apparent lack of nuclear immunoreactivity for Wilms tumor-1 protein (WT1) in the pulmonary metastasis of a morphologically typical case of nephroblastoma affecting a 6.5-year-old male prompted us to examine the expression of these 2 markers (and CD56) in a series of 48 nephroblastomas, 5 adult metanephric adenomas, and 1 pediatric cystic nephroma. TTF-1 was found to be positive in 8 of 48 (16.6%) nephroblastomas and negative in all 5 metanephric adenomas. WT1 was positive in 43 of 48 (89.6%) nephroblastomas and 4 of 5 (80.0%) metanephric adenomas. CD56 was positive in 45 of 47 cases that were so tested (95.74%), but negative in all metanephric adenomas. The single cystic nephroma was TTF-1–negative, WT1–negative, and CD56-positive. The finding of TTF-1 expression in one sixth of nephroblastomas constitutes a potential source of misdiagnosis. The biologic significance of this surprising finding is unclear. It may reflect the embryonal nature of these tumors and may conceivably result—directly or indirectly—in interference with the transcriptional control of target genes and other molecular events in the pathway leading to the development of nephroblastoma.

*Department of Pathology, IRCCS-Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo

Centro Diagnostico Italiano (CDI), Anatomic Pathology Section, Milan

Department of Anatomic Pathology, Bellaria Hospital, University of Bologna, Bologna

Department of Pathology, Polyclinic Hospital of Bari, Bari, Italy

§Department of Pathology, Cook Children's Medical Center, Fort Worth, TX

Correspondence: Michele Bisceglia, MD, Unità Operativa di Anatomia Patologica, IRCCS—“Casa Sollievo della Sofferenza” Hospital, 71013-San Giovanni Rotondo (FG), Italy (e-mails:;

© 2009 Lippincott Williams & Wilkins, Inc.