Study of Epithelial-Mesenchymal Transition in 70 Endometrial Carcinosarcomas (ECS)
KK Van De Vijver, MA Castilla, L Romero, M Biscuola, G Moreno-Bueno, J Palacios, E Oliva. Maastricht University Medical Centre, Maastricht, Netherlands; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Instituto de Investigaciones Biomedicas, Madrid, Spain; Massachusetts General Hospital, Boston
Background: Epithelial-mesenchymal transition (EMT) is a process of cellular trans-differentiation by which epithelial cells lose polarity and cell-cell contacts, reorganize their cytoskeleton, acquire expression of mesenchymal markers and manifest a migratory phenotype. EMT occurs during embryogenesis and although implicated in tumor progression, its occurrence in human neoplasias is controversial. The goal of this study was to compare cadherin switching, expression of mesenchymal markers and snail in the epithelial component of ECS and endometrial endometrioid carcinomas (EEC) in order to know if ECS can be considered a true example of EMT in human neoplasias.
Design: Expression of E-cadherin, N-cadherin and mesenchymal markers (SPARC and fascin) was analyzed by immunohistochemistry on the epithelial component of 70 ECS and 44 grade I and II EECs on tissue microarray sections. Expression for all markers was scored as absent, mild or moderate/intense according to intensity and extension. In addition, mRNA SNAI1 expression was analyzed by real time quantitative RT-PCR in both the epithelial and sarcomatous components of 22 ECS.
Results: Of the 70 ECS, 65 showed an intermingled distribution of carcinoma and sarcomatous components while in 5 the two components appeared to collide. Absent or mild E-cadherin expression was found in 43% ECS and 16% EEC (p= 0.005). Moderate/intense expression of N-cadherin, SPARC and fascin was observed in 38%, 35%, and 33% ECS, but in only 7%, 12%, and 0 EEC (p< 0.01 for all comparisons). E-cadherin was absent but SPARC and fascin were expressed at different levels in the sarcomatous component of all ECS. 90% ECS expressed detectable SNAI1 mRNA in the sarcomatous component but only 50% in the epithelial component. In addition, mean SNAI1 mRNA level was ten-fold higher in the sarcomatous than in the epithelial component.
Conclusions: Switching of cadherin subtypes and expression of snail and mesenchymal markers in the epithelial component of ECS indicate that this tumor represent a true example of stable EMT. Cadherin switching and expression of mesenchymal markers by epithelial cancer cells probably signal EMT capabilities in ECS. Once EMT is established, snail expression probably is necessary to maintain the mesenchymal phenotype in the sarcomatous component.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 2:45 PM
Platform Session: Section C, Monday Afternoon