In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 465-465
Abstract:
465 Background: Members of the Wnt/ß-catenin signaling pathway are abnormally expressed in renal cell carcinoma (RCC). This study analyzed the role of Wnt1/ß-catenin alterations in clear cell RCC (ccRCC) with regard to clinicopathology, overall survival (OS) and cancer specific survival (CSS) to prove the options of a Wnt targeted therapy. Methods: Corresponding ccRCCs and benign renal tissue were analyzed in 278 patients for Wnt1 and ß-catenin by immunohistochemistry in tissue microarrays. Expression scores including intensity and percentage of stained cells were compared between normal kidney and ccRCCs. Data was categorized according to the mean expressions core and correlated to tumor and patients’ characteristics and analyzed for OS and CSS according to the Kaplan-Meier and log-rank test. To identify prognostics value of wnt1 and ß-catenin, univariable and multivariable Cox proportional hazard regression models were used. Results: High Wnt1 tumor expression was associated with increased tumor diameter (p=0.01), stage (p=0.004) and vascular invasion (p=0.02). Positive membranous ß-catenin was associated with advanced stage (p=0.003), vascular invasion (p=0.01) and tumor necrosis (p=0.004). Increased tumor diameter (p=0.01), stage (p=0.003), node involvement (0.04), grade (p=0.001), vascular invasion (p=0.002), and sarcomatoid differentiation (p=0.01) were found in patients with high cytoplasmic ß-catenin. Furthermore, this patient subgroup showed reduced OS (p=0.03) and CSS (p=0.009). Conclusions: Significant clinicopathological associations underline the oncogenic potential of Wnt1/ß-catenin pathway parameters. Whereas, cytoplasmic ß-catenin was identified as the most valuable parameter with regard to clinico-prognostic implications for future targeted therapies.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2014.32.4_suppl.465
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2014
detail.hit.zdb_id:
2005181-5
