[781] 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).

Table 1: Composite Score Expression in SC and CC

Marker	% SC¤	% CC¤	Mean Difference	McNemar's Test P-value
E-cadherin	5	48	-2.4*	0.004
N-cadherin	95	95	0.2	1.000
β-catenin (membranous)	24	95	-3.3*	<0.0001
β-catenin (cytoplasmic)	52	22	1.9*	0.03
Snail	100	81	1.0*	0.046
SPARC	100	48	1.9*	0.0009

¤percent with moderate/strong expression (composite score 4-6); *statistically significant


Conclusions: E- to N-cadherin switching, dissemination of β-catenin into the cytoplasm, and increased expression of Snail and SPARC in SC indicate that SRCC is an example of EMT. Increased expression of N-cadherin and Snail in CC suggest involvement in initiating EMT, before mesenchymal phenotypic expression. Once EMT is established, the loss of E-cadherin, release of β-catenin into the cytoplasm, and expression of SPARC correspond with SC seen in SRCC. Future studies will compare these markers in CC to non-sarcomatoid renal cell carcinomas.
Category: Genitourinary (including renal tumors)

Monday, February 28, 2011 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 115, Monday Morning