Clinical and biologic significance of nuclear unrest in Wilms tumor

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Abstract
BACKGROUND Nuclear unrest is a term applied to Wilms tumors (WT) with favorable histology that show nuclear enlargement similar to that seen in anaplasia but with no abnormal mitotic figures. This study was undertaken to evaluate the clinical and pathogenetic significance of WT with nuclear unrest. METHODS The authors reviewed primary nephrectomy specimens and clinical data from 173 patients who were treated for WT on 1 of 5 consecutive clinical trials at St. Jude Children's Research Hospital. A subset of 70 patients was selected for p53 immunohistochemistry. Seventeen samples of recurrent tumors were also reviewed. RESULTS WT with nuclear unrest had age and stage distribution similar to that for WT with favorable histology. Patients who had tumors with favorable histology, nuclear unrest, and anaplastic histology had 5-year cumulative incidences of recurrence of 12.2%, 22.2%, and 36.4%, respectively (P = 0.010). Despite the difference in recurrence incidence, patients who had tumors with nuclear unrest and patients who had tumors with favorable histology had nearly identical overall survival. Immunostaining for p53 was positive in 2 of 24 tumors (8.3%) with favorable histology, 1 of 25 tumors (4%) with nuclear unrest, and 16 of 21 tumors (76%) with anaplastic histology (P < 0.001). Histologic review of samples from recurrent tumors showed that 7 of 10 of primary tumors converted from favorable histology to either nuclear unrest or anaplastic histology in the recurrent tumor. CONCLUSIONS WT with nuclear unrest more closely resembles favorable histology than anaplastic histology, both clinically and pathogenetically. Analysis of samples from recurrent tumors suggests that WT with nuclear unrest represents an intermediary in the continuum from favorable histology to anaplastic histology. For treatment stratification, it is appropriate to continue grouping nuclear unrest with favorable histology, although a larger analysis will be necessary to confirm the current findings. Cancer 2003;97:2318–26. © 2003 American Cancer Society. DOI 10.1002/cncr.11325