Does Increasing Fuhrman Nuclear Grade Reflect Evolving Epithelial-Mesenchymal Transition in Clear Cell Renal Cell Carcinoma?
Joanna L Conant, Zhihua Peng, Mark F Evans, Shelly Naud, Kumarasen Cooper. University of Vermont College of Medicine, Burlington, VT
Background: We have previously demonstrated that sarcomatoid renal cell carcinoma (SRCC) is an example of epithelial-mesenchymal transition (EMT). E- to N-cadherin switching, dissociation of β-catenin from the membrane into the cytoplasm, and increased expression of Snail and SPARC confirmed that SRCC is an example of EMT. In general, all SRCC are considered Fuhrman nuclear grade 4. Nuclear grade is an important prognostic indicator in clear cell renal cell carcinoma (RCC). The goal of this study was to evaluate the expression of EMT markers in clear cell RCC, Fuhrman grades 1-4 (without a sarcomatoid component), to determine if there is a progression towards SRCC EMT with increasing nuclear grade.
Design: E-cadherin, N-cadherin, β-catenin, Snail, and SPARC expression was analyzed by immunohistochemistry on 40 formalin-fixed, paraffin-embedded clear cell RCC specimens, Fuhrman nuclear grades 1-4. Expression was scored as absent, mild, moderate, or strong according to intensity and extent (composite score 0-6).
Results: Expression of E-cadherin, cytoplasmic N-cadherin, and cytoplasmic β-catenin increased with increasing Fuhrman nuclear grade (Spearman 0.33, 0.59, and 0.40, respectively). The expression of all remaining EMT markers did not differ significantly with Fuhrman nuclear grade (Figure 1).
Conclusions: With increasing Fuhrman nuclear grade, there is a progressive increase in cytoplasmic expression of N-cadherin and β-catenin. While not statistically significant, there is a trend toward progressive decrease in membranous expression of these two markers, suggesting that N-cadherin and β-catenin dissociate from the membrane and into the cytoplasm as nuclear grade increases, representing potentially incipient EMT with increasing Fuhrman nuclear grade.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 164, Monday Morning