Abstract 2269: Loss of NDRG2 expression is an independent prognostic factor in patients with localized clear cell renal cell carcinoma
Authors: Lee Hyo Jin , Liang Zhe Long , Huang Song Mei , Yun Hwan Jung , Jo Deog Yeon , Kim Samyong , Lim Jong Seok , Kim Jin Man 
Published: June 2012

Background: NDRG2 is a candidate tumor suppressor because it induced apoptosis and was down-regulated or absent in some cancers. About renal cell carcinoma it has been reported that NDRG2 inhibit the proliferation of clear cell RCC (CCRCC) cell and induce arrest at G1 phase. Moreover, NDRG2 were down-regulated in fresh CCRCC tissues, suggesting NDRG2 may play an important role in the development of CCRCC as a tumor suppressor. However, the clinical effect of NDRG2 expression in RCC has not been previously investigated.

Method: NDRG2 mAb was generated using recombinant protein consisting of aminoacids 150-337 of NDRG2 (NM_201541). The expression of NDRG2 proteins were studied by immunohistochemistry in 112 TMA of patients who underwent nephrectomy for localized CCRCC. Tumors were classified into four grades based on the staining intensity (0, no staining intensity; +1, weak; +2, intermediate; +3, strong). The cases with 0 staining intensity were considered the NDRG2-negative group, whereas those with +1 to +3 staining intensity were considered the NDRG2-positive group. Correlations between NDRG2 expression and clinicopathologic features as well as patient survival were determined.

Results: A total of 7 cases (6.3%) showed 0 staining intensity (NDRG2-negative group), whereas 105 cases showed +1 (35 cases), +2 (33 cases), or +3 (37 cases) staining intensity (NDRG2-positive group). NDRG2-negative tumors tended to show higher T stage (pT2-3) compared to NDRG2-positive group (85.7% vs. 55.2%). Furthermore, NDRG2-negative group was significantly associated with higher proportion of tumor larger than 10 cm (P = .012) and higher nuclear grade (P = .003). About survival, the 5-year recurrence-free survival (RFS) rates of the NDRG2-positive and -negative group were 86.7% and 28.6%, respectively (P &lt; .001), and the rates of 5-year disease-specific survival (DSS) for NDRG2-positive and -negative group were 92.4% and 28.6%, respectively (P &lt; .001). Univariate analyses indicated that Fuhrman nuclear grade (P = .009) and loss of NDRG2 expression (P &lt; .001) were statistically significant risk factors affecting RFS of CCRCC patients. About DSS, Fuhrman nuclear grade (P = .005) and loss of NDRG2 expression (P &lt; .001) were also significant risk factors. Furthermore, Multivariate analyses showed that Fuhrman nuclear grade (HR, 2.990; P = .025) and loss of NDRG2 expression (HR, 7.901; P &lt;.001) were independent risk factors predicting RFS of CCRCC patients. Loss of NDRG2 expression was still an independent prognostic factor (HR, 15.395; P &lt; .001) for DSS.

Conclusion: NDRD2 expression was lost in some population of CCRCC patients, and loss of NDRG2 expression was correlated with larger tumor size and higher nuclear grade. Furthermore, loss of NDRG2 expression was an independent poor prognostic factor predicting RFS and DSS, suggesting that it could be a useful marker to predict outcomes in patients with CCRCC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2269. doi:10.1158/1538-7445.AM2011-2269