Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma. Issue 8 (18th January 2013)

• Record Type: Journal Article
• Authors: Kroeger, Nils; Klatte, Tobias; Chamie, Karim; Rao, P. Nagesh; Birkhäuser, Frédéric D.; Sonn, Geoffrey A.; Riss, Joseph; Kabbinavar, Fairooz F.; Belldegrun, Arie S.; Pantuck, Allan J.
• Is Part Of: Cancer. Volume 119:Issue 8(2013)
• Page Start: 1547
• Page End: 1554
• Publication Date: 2013-01-18
• Subjects: renal cell carcinoma -- von Hippel‐Lindau deletion -- hypoxia‐inducible factor 1α -- tumor suppressor gene -- cancer‐specific survival -- recurrence‐free survival; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.27947
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract: BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel‐Lindau ( VHL ) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia‐inducible factor 1α ( HIF‐1α ) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF‐1α gene) in clear cell renal cell carcinoma (ccRCC). METHODS: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL‐WT]), VHL +3p/−14q (VHL‐WT plus HIF2α [WT/H2]), −3p/+14q (HIF1α and HIF2α [H1H2]), and −3p/−14q (HIF2α [H2]). RESULTS: Among patients who had loss of 3p, tumors with −3p/−14q (H2) alterations were larger ( P = .002), had higher grade ( P = .002) and stage ( P = .001), and more often were metastatic ( P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with −3p/−14q (H2) had worse cancer‐specific survival ( P = .014), and patients who had localized disease ( P = .012) and primary T1 (pT1) tumors ( P = .008) had worse recurrence‐free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence‐free survival (hazard ratio, 11.19; 95% confidence interval, 1.91‐65.63) and cancer‐specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09‐82.16). The current investigation was limited by its retrospective design, single‐center experience, and a lack of confirmatory protein analyses. CONCLUSIONS: Loss of chromosome 3p (the VHL gene ) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF‐1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF‐1α functions as an important tumor suppressor gene in ccRCC. Cancer 2013. © 2013 American Cancer Society. Abstract : In patients with clear cell renal cell carcinoma, loss of the von Hippel‐Lindau ( VHL ) gene is associated with more favorable pathologic features and with improved recurrence‐free and cancer‐specific survival, whereas loss of the hypoxia‐inducible factor 1α ( HIF‐1α ) gene is associated with worse recurrence‐free and cancer‐specific survival. Combined loss of chromosome 3p/14q is a strong predictor of disease recurrence in patients with low‐stage (pathologic T1) renal cell carcinoma, supporting the hypothesis that HIF‐1α functions as a tumor suppressor gene in clear cell renal cell carcinoma.