Abstract
ObjectivesIn patients with cancer, myoferlin protein hyperexpression has been correlated with poor patient prognosis. Here, we evaluated myoferlin expression in patients with clear cell renal cell carcinoma (ccRCC) and investigated the prognostic significance of myoferlin expression in these patients.Materials and MethodsOne hundred and fifty-two patients with ccRCC who underwent treatment at Gyeongsang National University Hospital, Korea, between January 2000 and December 2009 were enrolled. Immunohistochemical analysis was performed on tissue microarray blocks produced from surgical specimens. Surgical specimen cancerous cells were graded as showing myoferlin hyperexpression or hypoexpression by comparison with intratumoral endothelial cells. Disease-free survival was evaluated using Kaplan-Meier analysis. Cox regression analysis was used to determine the relationships between myoferlin expression levels, risk factors, and prognosis.ResultsSeventy-one of 304 cores exhibited myoferlin hyperexpression. T stage was not associated with myoferlin hyperexpression, whereas a high Fuhrman nuclear grade was significantly associated with myoferlin hyperexpression. Kaplan-Meier analysis revealed that patients with T stage >2, Fuhrman nuclear grade >2, and those with myoferlin hyperexpression had poorer disease-free survival compared to those with lower T stage, lower Fuhrman nuclear grade, and myoferlin hypoexpression (all p <0.001). Furthermore, myoferlin hyperexpression was significantly associated with disease-free survival on Cox regression analysis (hazard ratio, 4.604; 95% confidence interval, 1.893–11.199; p = 0.001).ConclusionMyoferlin expression could be a potential prognosticator in patients with ccRCC, and might be a useful marker for oncologic surveillance in such patients.
Highlights
Clear cell renal cell carcinoma accounts for 70–80% of RCCs [1], and ~20–30% of these patients progress to an advanced stage after surgery [2]
T stage was not associated with myoferlin hyperexpression, whereas a high Fuhrman nuclear grade was significantly associated with myoferlin hyperexpression
Kaplan-Meier analysis revealed that patients with T stage >2, Fuhrman nuclear grade >2, and those with myoferlin hyperexpression had poorer disease-free survival compared to those with lower T stage, lower Fuhrman nuclear grade, and myoferlin hypoexpression
Summary
Clear cell renal cell carcinoma (ccRCC) accounts for 70–80% of RCCs [1], and ~20–30% of these patients progress to an advanced stage (recurrence or distant metastasis) after surgery [2]. The tumor-node-metastasis staging of the American Joint Committee on Cancer (AJCC) [5] and Fuhrman nuclear grade [6] are well established predictive risk factors for recurrence. Myoferlin protein expression has been recently associated with poor prognosis in patients with cancer [7,8,9]. Fer-1 defects have been associated with infertility due to the abnormal fusion of cellular membranes in developing sperm [11]. In normal embryonic development or muscle regeneration, myoferlin is highly expressed during myoblast fusion [12]. The physiological function(s) of myoferlin have not been fully elucidated
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