Sarcomatoid Renal Cell Carcinoma Is an Example of Epithelial-Mesenchymal Transition.
Joanna L Conant, Zhihua Peng, Mark F Evans, Shelly Naud, Kumarasen C Cooper. University of Vermont College of Medicine, Burlington
Background: Sarcomatoid renal cell carcinomas (SRCC) are composed of a sarcomatous component (SC) and a carcinomatous component (CC). Studies suggest that mesenchymal cells in SC have undergone a morphologic change from their epithelial origin through a process known as epithelial-mesenchymal transition (EMT). In EMT, cells lose their epithelial characteristics and gain a mesenchymal phenotype, leading to an increased ability to migrate and metastasize. The goal of this study was to evaluate cadherin switching, membranous vs. cytoplasmic/nuclear localization of β-catenin, and expression of Snail (Snai1, an E-cadherin transcriptional repressor) and SPARC (a mesenchymal marker) in SC and CC to determine if SRCC is an example of EMT.
Design: E-cadherin, N-cadherin, β-catenin, Snail, and SPARC expression was analyzed by immunohistochemistry on SC and CC of 21 formalin-fixed, paraffin-embedded SRCC specimens. Expression was scored as absent, mild, moderate, or strong according to intensity and extent (composite score 0-6).
Results: E-cadherin expression was decreased in SC compared to CC (Wilcoxon signed-rank test, p=0.0004) while N-cadherin expression was similar (p=0.46). Membranous β-catenin expression was decreased in SC (p<0.0001), but cytoplasmic expression was increased (p=0.0002). No nuclear expression of β-catenin was seen. Snail and SPARC were more likely to be expressed in SC (p=0.002 and <0.0001). When the scores were dichotomized into absent/mild and moderate/strong expression levels, the results using McNemar's test substantiated the results above (Table 1).
|Marker||% SC¤||% CC¤||Mean Difference||McNemar's Test P-value|