Chromosome 17p13 deletion is associated with an aggressive tumor phenotype in clear cell renal cell carcinoma

Abstract

Background: Deletions of 17p13 recurrently occur in renal cell carcinoma (RCC) but their prognostic role seems to be uncertain. Methods: To determine prevalence, relationship with tumor phenotype, and patient prognosis, a tissue microarray containing samples from 1809 RCCs was evaluated using dual labeling fluorescence in situ hybridization (FISH) with 17p13 and chromosome 17 centromere probes. Results: A 17p13 deletion was found in 72 of 1429 interpretable tumors. The frequency of 17p13 deletions varied greatly between RCC subtypes and was highest in chromophobe RCC (24/72; 33.3%). 17p13 deletions were also found in 35 (3.7%) of 946 clear cell RCC, 9 (4.3%) of 208 papillary RCC, 1 of 121 oncocytomas (0.8%), as well as in several rare cases of comprising 1 of 7 Xp11.2 translocation cancers, 1 of 3 collecting duct carcinomas, and 1 of 20 not otherwise specified (NOS) carcinomas. In clear cell carcinomas, 17p13 deletions revealed a strong and consistent association with higher Fuhrman, ISUP, and Thoenes grade (p < 0.0001 each), and linked to advanced tumor stage (p = 0.0168), large tumor diameter (p = 0.0004), distant metastases (p = 0.0077), cancer-specific survival (p = 0.0391), and recurrence-free survival (p = 0.0072). In multivariate analysis, 17p13 deletions showed in clear cell RCC a dependent prognostic role for established clinical-pathological parameters. Conclusion: 17p13 deletions have a dual role in RCC. They are associated with disease progression in clear cell RCC and possibly other subtypes and they are linked to the development of chromophobe RCC-a subtype with a particularly favorable prognosis.

Risk prediction for metastasis of clear cell renal cell carcinoma using digital multiplex ligation‐dependent probe amplification

“…More specifically, losses in 3p are important for diagnosis and losses in 9p or 14q are important for prognosis. The Cancer Genomics Consortium Workgroup also reported that the TP53 mutation had clinical significance for prognosis, and deletions on 17p13, carrying TP53 , was added as a risk factor because this region is associated with an aggressive tumor phenotype 24,25 . Loss of chromosome 4 is not as well known as losses of chromosome 9 and 14q, but has been reported to be positively correlated with high tumor grade and candidate tumor suppressor genes 26‐28 .…”

“…The Cancer Genomics Consortium Workgroup also reported that the TP53 mutation had clinical significance for prognosis, and deletions on 17p13, carrying TP53, was added as a risk factor because this region is associated with an aggressive tumor phenotype. 24,25 Loss of chromosome 4 is not as well known as losses of chromosome 9 and 14q, but has been reported to be positively correlated with high tumor grade and candidate tumor suppressor genes. [26][27][28] In our ccRCCs, losses in 3p were detected in 56/60 (93.3%) and 5q gain was detected in 31/60 (51.7%).…”

Napsin A Expression in Human Tumors and Normal Tissues

“…To thoroughly analyze the potential prognostic value of Napsin A, the subset was separately analyzed at two different antibody dilutions (1:400 and 1:135). This subset of renal cell carcinomas with clinicopathological information has been used in several previously published studies (for example [36][37][38][39][40][41][42]).…”