PURPOSE: To evaluate the expression of multiple molecular markers associated with autophagy, a cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles, in clear cell renal cell carcinoma (CCRCC) in order to identify the prognostic significance of these markers in patients undergoing radical nephrectomy. METHODS: Expression levels of five markers, including autophagy-related gene 5 (Atg5), Atg9, Beclin 1, microtubule-associated protein light chain 3 (LC3), and UNC-51-like kinase 1 (ULK1), in radical nephrectomy specimens from a total of 100 patients with non-metastatic CCRCC were measured by immunohistochemical staining. RESULTS: All the five markers were significantly correlated with some pathological factors reflecting an aggressive phenotype, including the pathological T stage, tumor grade, and microvascular invasion. During the follow-up period of this series (median 58.0 months), disease recurrence developed in 41 of the 100 patients, with a 5-year recurrence-free survival (RFS) rate of 61.3%. On univariate analysis, expression levels of Atg5 and Beclin 1, in addition to the pathological T stage, microvascular invasion, and preoperative CRP level, were identified as significant predictors of disease recurrence. Of these factors, the expression of Beclin 1 and preoperative CRP level were independently correlated with RFS on multivariate analysis. CONCLUSION: These findings suggest that the combined assessment of expression levels of autophagy-associated markers, particularly Beclin 1, in radical nephrectomy specimens with conventional prognostic parameters, would contribute to the precise prediction of postoperative disease recurrence in patients with non-metastatic CCRCC.
PURPOSE: To evaluate the expression of multiple molecular markers associated with autophagy, a cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles, in clear cell renal cell carcinoma (CCRCC) in order to identify the prognostic significance of these markers in patients undergoing radical nephrectomy. METHODS: Expression levels of five markers, including autophagy-related gene 5 (Atg5), Atg9, Beclin 1, microtubule-associated protein light chain 3 (LC3), and UNC-51-like kinase 1 (ULK1), in radical nephrectomy specimens from a total of 100 patients with non-metastatic CCRCC were measured by immunohistochemical staining. RESULTS: All the five markers were significantly correlated with some pathological factors reflecting an aggressive phenotype, including the pathological T stage, tumor grade, and microvascular invasion. During the follow-up period of this series (median 58.0 months), disease recurrence developed in 41 of the 100 patients, with a 5-year recurrence-free survival (RFS) rate of 61.3%. On univariate analysis, expression levels of Atg5 and Beclin 1, in addition to the pathological T stage, microvascular invasion, and preoperative CRP level, were identified as significant predictors of disease recurrence. Of these factors, the expression of Beclin 1 and preoperative CRP level were independently correlated with RFS on multivariate analysis. CONCLUSION: These findings suggest that the combined assessment of expression levels of autophagy-associated markers, particularly Beclin 1, in radical nephrectomy specimens with conventional prognostic parameters, would contribute to the precise prediction of postoperative disease recurrence in patients with non-metastatic CCRCC.
Authors: Tobias Klatte; David B Seligson; Jeffrey LaRochelle; Brian Shuch; Jonathan W Said; Stephen B Riggs; Nazy Zomorodian; Fairooz F Kabbinavar; Allan J Pantuck; Arie S Belldegrun Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-02-24 Impact factor: 4.254
Authors: Maxine Sun; Shahrokh F Shariat; Christopher Cheng; Vincenzo Ficarra; Masaru Murai; Stéphane Oudard; Allan J Pantuck; Richard Zigeuner; Pierre I Karakiewicz Journal: Eur Urol Date: 2011-06-30 Impact factor: 20.096
Authors: M K Kashyap; A Kumar; N Emelianenko; A Kashyap; R Kaushik; R Huang; M Khullar; S K Sharma; S K Singh; A K Bhargave; S K Upadhyaya Journal: Biomarkers Date: 2005 Jul-Aug Impact factor: 2.658
Authors: S P K Jagdev; W Gregory; N S Vasudev; P Harnden; S Sim; D Thompson; J Cartledge; P J Selby; R E Banks Journal: Br J Cancer Date: 2010-11-09 Impact factor: 7.640