Comparison of digital image analysis versus visual assessment to assess survivin expression as an independent predictor of survival for patients with clear cell renal cell carcinoma

SummaryWe previously used quantitative digital image analysis to report that high immunohistochemical tumor expression levels of survivin independently predict poor outcome among patients with clear cell renal cell carcinoma. However, given the cumbersome and costly nature of digital image analysis, we evaluated simple visual assessment as an alternative to digital image analysis for assessing survivin as a predictor of clear cell renal cell carcinoma patient outcomes. We identified 310 patients treated surgically for unilateral, sporadic, clear cell renal cell carcinoma at our institution between 1990 and 1994. Survivin expression was quantified independently by digital image analysis and visual assessment in paraffin slides using a commercially available antibody. We examined the agreement between the 2 methods using the κ statistic and then used Cox regression to compare the ability of the 2 methods to predict renal cell carcinoma death. The κ statistic comparing high survivin expression determined by digital image analysis versus visual assessment was .68, indicating substantial agreement between the 2 methods. Moreover, even after multivariate adjustment, the association of high survivin expression with risk of renal cell carcinoma death was similar for both visual assessment (risk ratio = 2.01; 95% confidence interval, 1.26-3.22) and digital image analysis (risk ratio = 1.75; 95% confidence interval, 1.10-2.80). Finally, among patients with “moderate risk” (Stage, Size, Grade, and Necrosis scores 3-6) and “high risk” (Stage, Size, Grade, and Necrosis scores 7 or greater) clear cell renal cell carcinoma, high survivin expression determined by visual assessment was significantly associated with poorer survival (P = .006 and P = .017, respectively). Herein, we demonstrate substantial agreement between survivin quantification by digital image analysis and visual assessment. We further confirm that high survivin expression assessed by visual assessment remains an independent predictor of aggressive clear cell renal cell carcinoma behavior. Thus, visual assessment represents an economical, widely available, and reliable method to assess survivin as a predictor of clear cell renal cell carcinoma patient outcomes.