Automated Image Analysis of Endoglin and Microvascular Density in Clear Cell Renal Cell Carcinoma and Its Prognostic Significance.
William Dubinski, Manal Gabril, Vladimir Iakovlev, Youssef Youssef, Kalman Kovacs, Shereen Metias, Fabio Rotando, Madeleine Moussa, Cathy Streutker, George M Yousef. St. Michael's Hospital, Toronto, ON, Canada; London Health Sciences Center, ON, Canada
Background: The metastatic potential of clear cell renal cell carcinoma (ccRCC) is related to tumor angiogenesis. Assessment of angiogenesis by quantifying intratumoral microvascular density (IMVD) may prove to be a useful prognostic parameter in ccRCC. Endoglin is a novel vascular marker that correlates with prognosis in numerous tumors. In this study, we provide the first automated digital assessment of IMVD in ccRCC using endoglin and CD31 and compare our findings with clinical outcome data. This automated approach overcomes many of the limitations of manual quantification.
Design: Fifty cases of ccRCC were immunostained for endoglin and CD31 to highlight tumor vasculature. Immunostained slides were scanned using an Aperio CS Scanner at 20× magnification, and image analysis was used to count IMVD and nuclear density within tumoral and adjacent normal kidney. Clinicopathologic parameters (age, tumor size, follow–up time, nuclear grade and tumor stage) were collected and correlated statistically with IMVD.
Results: Increased expression of endoglin and CD31 was associated with advanced tumor stage (p=0.026 and p=0.039, respectively). There was no correlation between tumor grade and endoglin or CD31 expression (p=0.30). Using a binary cut-off, endoglin-positive patients had significantly lower progression-free survival (p=0.017) compared to endoglin-negative patients. Using endoglin as a continuous variable, increased endoglin expression was associated with reduced survival (HR: 1.87, CI 1.39-2.53, p= <0.001). CD31 positive patients had a tendency for shorter progression-free survival but this was not statistically significant (p=0.13). There was no correlation between CD31 and endoglin expression (r= -0.120, p=0.536). Receiver operating characteristic (ROC) curves showed that the combination between CD31 and CD34 showed the best performance (AUC = 0.81, 95%CI=0.64-0.99; p<0.028), followed by CD34 and Endoglin (AUC= 0.79).
Conclusions: Automated image analysis of endoglin and CD31 expression in ccRCC showed that increased IMVD is associated with higher tumor stage and decreased survival. The advances in digital assessment of immunohistochemical expression can be helpful in evaluating and establishing the clinical significance of new prognostic markers for renal cell carcinoma.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 116, Monday Morning