Chromosome 20q13.2 Gain May Predict Intravesical Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Tumors

Abstract

Purpose: Amplification or gain of copy number of chromosome 20q13.2 has been implicated as a causal factor for chromosome instability.We investigated the impact of chromosomal instability and its causative molecular markers, 20q13.2 gain and centrosome amplification, on patient outcome in upper urinary tract transitional cell carcinoma (UUT-TCC). Experimental Design: The number of centrosomes was assessed by immunohistochemistry. Numerical aberrations of chromosomes 7, 9, and 17 that allowed the estimation of chromosomal instability and 20q13.2 gain were evaluated by fluorescence in situ hybridization in 96 frozen specimens from UUT-TCC and compared with clinicopathologic background and patient outcome. Results: Chromosomal instability, 20q13.2 gain, and centrosome amplification were detected in 62 of 96 (64.6%), 61of 96 (63.5%), and 45 of 90 (50.0%) tumors, respectively. 20q13.2 Gain was significantly associated with tumor stage (P = 0.042), chromosomal instability (P < 0.0001), and centrosome amplification (P < 0.0001). Kaplan-Meier analysis showed that 20q13.2 gain was strongly associated with intravesical recurrence-free survival in all patients (P = 0.0050), as well as in patients with grade 2 tumors (P = 0.0011, log-rank test). On multivariate analysis, 20q13.2 gain was found to be the sole independent prognostic factor predicting subsequent intravesical recurrence (hazard ratio, 1.65; 95% confidence interval, 1.03^2.90; P = 0.036). Conclusions: 20q13.2 gain was strongly associated with a reduced time to intravesical recurrence in all patients. Our data suggest that 20q13.2 gain may be a predictive marker of intravesical recurrence in patients with UUT-TCC.

Genomic profiling of sinonasal squamous cell carcinoma

“…33 The 20q13 chromosomal region, however, is very gene rich, and there may be other candidate genes explaining the relation to metastasis. Gains and amplifications of the 20q13.2 region have been correlated with lymph node status in gastric cancer, 34 with recurrence in urothelial tumors, 35 and with tumor progression in colorectal carcinoma. 36 This preliminary finding needs to be confirmed in studies with a larger number of cases.…”

Centrosome amplification as a putative prognostic biomarker for the classification of urothelial carcinomas

“…aCGH analysis) and CIN (in FISH analysis) than those without it, and this association was more significant than that between tumor grade and DCNAs/CIN. Recent studies have reported that CA is closely related to the phenotypes of high tumor grade and CIN in human malignancies [12,13] including urothelial carcinomas of the bladder [15] and upper urinary tract [14]. It was also reported that, in an aCGH analysis of urothelial carcinomas, high-grade tumors contained DNA copy number gains and amplifications considerably more frequently than low-grade tumors [23].…”

“…We retrospectively reviewed the records of these patients. Follow-up included regular clinical examination as described previously [14,16]. Tumor recurrence was defined as a new tumor detected either by regular follow-up cystoscopy for local recurrence or by radiographic imaging for distant metastasis.…”

“…Accumulating evidence suggests that centrosome amplification (CA), which leads to the formation of multipolar spindles and unequal segregation of chromosomes, is both a common and major factor for CIN [6,11], notably in human malignancies [12][13][14]. Previous studies have reported that CA is closely related to tumor grade, DNA ploidy, and CIN in urothelial carcinoma [8,[14][15][16].…”

Intercellular centrosome number is correlated with the copy number of chromosomes in bladder cancer

“…Accumulating evidence has suggested that centrosome amplification, which leads to the formation of multipolar spindles and unequal segregation of chromosomes, is both a common and major factor for chromosomal instability (CIN) [1] [2] in several human malignancies [3][4][5]. Previous studies have reported that centrosome amplification is closely related not only to the tumor grade and DNA ploidy but also to CIN in bladder cancer [6][7][8].…”