scholarly journals Higher Expression of Topoisomerase II Alpha Is an Independent Marker of Increased Risk of Cancer-specific Death in Patients with Clear Cell Renal Cell Carcinoma

2014 ◽  
Vol 66 (5) ◽  
pp. 929-935 ◽  
Author(s):  
Alexander S. Parker ◽  
Jeanette E. Eckel-Passow ◽  
Daniel Serie ◽  
Tracy Hilton ◽  
Mansi Parasramka ◽  
...  
2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
Faithlore Patrice Gardner ◽  
Richard Wayne Joseph ◽  
Daniel Serie ◽  
Tracy W. Hilton ◽  
Mansi Parasramka ◽  
...  

446 Background: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. Methods: We identified 947 patients who underwent nephrectomy to treat clinically localized ccRCC between January 16, 1990, and September 27, 2006. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features, we employed Kruskal-Wallis tests and for associations with cancer-specific survival, we generated Cox proportional hazard regression models. Results: HigherTOP2a expression is associated with later stage, higher grade and higher Mayo SSIGN score (all p < 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend < 0.0001). Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.31 95% CI 1.64-3.25; p < 0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ~95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.09 95% CI 1.29-7.40; p = 0.01). Conclusions: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15539-e15539
Author(s):  
Faithlore Patrice Gardner ◽  
Richard Wayne Joseph ◽  
Daniel Serie ◽  
Tracy W. Hilton ◽  
Mansi Parasramka ◽  
...  

e15539 Background: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. Methods: We identified 1,380 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/16/1990 and 4/14/2009. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features we employed Kruskal-Wallis tests and for associations with cancer-specific survival we generated Cox proportional hazard regression models. Results: HigherTOP2a expression is associated with later stage, higher grade and higher MayoSSIGN score (all p < 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend < 0.0001), and this association remained strong after after multivariate adjustment for well-known predictors of RCC aggressiveness. Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.62 95% CI 1.95-3.54; p<0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ~95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.48 95% CI 1.56-7.76; p =0.002). Conclusions: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160570 ◽  
Author(s):  
Vesna M. Coric ◽  
Tatjana P. Simic ◽  
Tatjana D. Pekmezovic ◽  
Gordana M. Basta-Jovanovic ◽  
Ana R. Savic Radojevic ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-3
Author(s):  
Jessica Tran ◽  
Auris Huen ◽  
Madeleine Duvic

Patients with mycosis fungoides have an increased risk for additional malignancies, particularly hematologic malignancies. Of the malignancies that have been associated with mycosis fungoides, renal cell carcinoma and other solid tumor malignancies have not been studied extensively. In this case series, we describe three mycosis fungoides patients who were diagnosed with clear cell renal cell carcinoma and discuss the potential pathophysiology underlying this association.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yunlai Zhi ◽  
Xiao Li ◽  
Feng Qi ◽  
Xin Hu ◽  
Wenbo Xu

The purpose of this article was to explore the association of tumor size with lymph node metastases (LNM) risk in patients with clear cell renal cell carcinoma (ccRCC). Based on the Surveillance, Epidemiology, and End Result (SEER) database, patients diagnosed with ccRCC from 1988 to 2015 were included in this study. For each patient, personal characteristics, clinicopathological data, and survival outcomes were, respectively, collected. Subsequently, the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to investigate the potential risk factors for LNM in ccRCC. Finally, Kaplan-Meier (KM) survival plots of overall survival (OS) and ccRCC-specific survival (CSS) were evaluated on the basis of different tumor sizes. A total of 8,292 patients were finally enrolled in the study, 1,170 of whom (14.11%) had LNM. According to the heatmap, we could intuitively interpret that larger tumor size was related to an increased risk of LNM obviously. The risk of LNM was evidently greater for larger tumor size (4-7 cm: OR = 2.415, 95% CI = 1.708–3.415; 7–10 cm: OR = 3.746, 95% CI = 2.677–5.242; and >10 cm: OR = 4.617, 95% CI = 3.302–6.457) compared with smaller tumor size (≤4 cm). According to the KM survival plots of OS and CSS, we observed a gradual decline in survival with increasing tumor size, while the smallest tumor size had the best survival outcomes. These results indicated the positive relationship of tumor size with risk of LNM in ccRCC. And we also noticed continual decrease survival rates of OS and CSS with increasing tumor size.


Cancer ◽  
2013 ◽  
Vol 120 (7) ◽  
pp. 1059-1067 ◽  
Author(s):  
Richard W. Joseph ◽  
Payal Kapur ◽  
Daniel J. Serie ◽  
Jeanette E. Eckel-Passow ◽  
Mansi Parasramka ◽  
...  

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 516-516
Author(s):  
Sarah P. Psutka ◽  
Suzanne B. Stewart ◽  
Christine M. Lohse ◽  
Matthew K. Tollefson ◽  
Stephen A. Boorjian ◽  
...  

516 Background: The impact of diabetes mellitus (DM) on outcomes in patients with renal cell carcinoma (RCC) is controversial. Herein, we evaluated the association of DM with survival among patients with RCC. Methods: We reviewed 2,589 patients treated with nephrectomy for sporadic, unilateral, M0 RCC between 1990 and 2008 and compared demographic and tumor characteristics in patients with and without DM (nonDM). Patients with DM (n=313) were matched 1:2 to nonDM patients according to date of surgery, age, smoking status, obesity, ECOG performance status (PS), CKD stage, histological subtype, and nuclear grade. Cancer-specific (CSS) and overall survival (OS) were compared by Kaplan-Meier analysis. The association of DM with outcomes was evaluated with Cox proportional hazards regression models. Results: A total of 313 (12%) patients had DM. DM patients were significantly older at RCC diagnosis, more likely to be obese, and had higher Charlson scores, CKD class, rates of smoking, and worse PS at surgery (p<0.001). Patients with DM were also more likely to have ccRCC (83% vs. 76%, p=0.02) and to undergo nephron-sparing surgery (42% vs. 35%, p=0.01), while other pathologic features were similar in DM and nonDM. Among the 939 matched cases and controls, 463 patients died within a median of 5.5 years after nephrectomy. Median follow-up for survivors was 8.6 years. Five-year CSS was not significantly different among DM patients 84% vs. nonDM patients 87% (p=0.11), although 5-year OS was significantly worse among DM patients (66% vs. 75%; p<0.001). Indeed, even after adjusting for Charlson score, DM patients were noted to have a significantly increased risk of all-cause mortality (HR 1.33; p=0.004). In a subanalysis of patients with clear cell RCC, DM patients were more likely to die from RCC compared with nonDM patients after adjusting for the SSIGN (Stage, Size, Grade, Necrosis) score (HR 1.44; p=0.034). Conclusions: In this surgical cohort, DM was independently associated with decreased CSS among patients with ccRCC and with decreased OS in all RCC subtypes. Further studies to determine the potential biologic mechanism for this interaction are warranted.


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