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Effects of Chemotherapy on the Cytogenetic Constitution of Wilms' Tumor

Authors' Affiliations: ¹ Department of Urology, University of Hamburg-Eppendorf, Hamburg, Germany; Departments of ² Pathology, ³ Medical Statistics, and ⁴ Urology, University of Göttingen, Göttingen, Germany; ⁵ Department of Pediatric Oncology, University of Homburg/Saar, Homburg/Saar, Germany; and ⁶ Department of Pediatric Pathology, University of Kiel, Kiel, Germany

Requests for reprints: László Füzesi, Department of Pathology, University of Göttingen, Robert-Koch-Strasse 40, D-37099 Göttingen, Germany. Phone: 49-551-396858; Fax: 49-551-398627; E-mail: fuezesi{at}med.uni-goettingen.de.

The management of Wilms' tumors consists of a combination of surgery, chemotherapy, and possibly radiotherapy. To date, chemotherapy is being risk stratified according to histologic subtype and stage. Although the cytogenetic characteristics of Wilms' tumors are well established, the cytogenetic effects related to chemotherapy are widely unknown. We herein report on comparative genomic hybridization findings in 41 primary Wilms' tumors of blastemal type, of which 19 had received preoperative chemotherapy (PCT group) and 22 did not (non-PCT group). Overall, imbalances could be detected in 32 tumors, with +1q (17 cases), +7q (10 cases), +7p (6 cases), and –7p (6 cases) as the most common changes. Among these, +7q and –7p were both significantly associated with metastatic disease at the time of surgery (P = 0.002 and 0.007, respectively), and +7q was also associated with higher stage (stages III + IV; P = 0.003). There were significant differences in the cytogenetic constitution of tumors between the two treatment groups. As a trend, tumors in the preoperative-chemotheraphy group had fewer changes (mean, 2.7) than those in the non-preoperative-chemotheraphy group (mean, 3.8), and the frequencies of imbalances at 7p or +7q, respectively, were significantly lower compared with tumors in the non-preoperative-chemotheraphy group (2 of 19 versus 10 of 22, P = 0.019; 1 of 19 versus 9 of 22, P = 0.011). In contrast, –1q was common in both the preop-CT group (10 of 19) and the non-preop-CT group (7 of 22). The results suggest that Wilms' tumor clones with +1q are not obliterated by preoperative chemotherapy, whereas cytogenetically more complex clones with +7q and/or imbalances at 7p seem more responsive and are more likely to be eliminated by chemotherapeutic treatment.

Key Words: Pediatric cancers • Molecular cytogenetics