Use of chromosome 9p status to identify a subset of high-risk localized renal cell carcinoma

Abstract

5090 Background: We investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicts worse disease-specific (DSS) and recurrence-free survival (RFS), and if it is associated with worse prognosis in tumors < 4 cm. Methods: 316 patients undergoing nephrectomy prior to 2001 were included on a tissue microarray in whom FISH analysis using the LSI p16/CEP 9 Dual Color Probe was performed to assess chromosome 9p deletion status. An additional 389 patients undergoing nephrectomy after 2001 had 9p status determined by standard cytogenetics. Tumor grade, stage, size, 9p status, nodal involvement, and the presence of metastasis were recorded. Disease-specific and recurrence-free survival were determined, and independence was assessed using Cox proportional hazards models. Results: 9p deletions were detected in 14% of tumors. 54% of 9p-deleted tumors were high grade (G3–4) vs. 38% without 9p deletions, and 60% of 9p-deleted tumors were T3–4 vs 38% without 9p deletions (p < 0.01). 55% of those with 9p deletions had positive nodes or metastases vs. 34% of those without 9p deletions (p < 0.01). Median DSS for those with and without 9p deletions was 80 months and 37 months, respectively (p < 0.01). In localized disease, median RFS for those with 9p deletions was 53 months and was not reached in those without 9p deletions (p<0.01). In 188 patients presenting with localized RCC < 4 cm, loss of 9p occurred in 3/7 (42.9%) of patients with post-nephrectomy recurrence vs. 13/168 (7.2%) of patients without disease recurrence (p = 0.001). DSS for patients with 9p deletion in tumors < 4 cm was significantly worse than DSS in those without 9p deletions (HR 6.18; p = 0.02), and an independent effect on RFS was seen for 9p deletions in localized RCC (HR 2.3, p < 0.01). 9p status was not a significant predictor in metastatic RCC. Conclusions: Deletion of chromosome 9p in ccRCC occurs in 14% of patients and is associated with higher grade and T stage, presence of nodal and distant disease, worse prognosis, and in patients with small NOMO tumors, 9p deletions but not tumor size was independently associated with RFS. Identifying high risk patients with 9p deletions will allow better risk stratification for surveillance protocols and for adjuvant trials. No significant financial relationships to disclose.