Loss of E-Cadherin Is a Shared Feature of Both Sarcomatous and Undifferentiated Components of Uterine Carcinosarcomas and Dedifferentiated Carcinomas
OM Al-Agha, K Garg, LJ Tafe, D Huntsman, RA Soslow. British Columbia Cancer Agency, Vancouver, BC, Canada; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Uterine carcinosarcomas can resemble dedifferentiated endometrial carcinomas (i.e. combined differentiated and undifferentiated endometrial carcinomas). The distinction between carcinosarcoma and dedifferentiated carcinoma essentially depends on the presence of a sarcomatous component in the former even when undifferentiated foci are present in carcinosarcoma. We sought to study mechanisms responsible for mesenchymal differentiation in carcinosarcoma and loss of overt epithelial differentiation in dedifferentiated carcinomas. We hypothesized that loss of expression of the cell adhesion molecule, E-cadherin, would be a shared feature of the undifferentiated regions of these tumors and the sarcomatous regions of carcinosarcomas.
Design: The study comprised of 17 cases of carcinosarcoma and 14 endometrial carcinomas with undifferentiated components (either dedifferentiated or pure undifferentiated carcinomas). E-cadherin expression was examined by immunohistochemistry using an avidin conjugated monoclonal anti-E-cadherin antibody (DAKO, 1:125 dilution).
Results: E-cadherin expression was absent in undifferentiated and sarcomatous regions of 15 of 17 carcinosarcomas (88%) and 12 of 14 de-/undifferentiated carcinomas (86%). E-cadherin was strongly expressed in the carcinomatous components of all 17 carcinosarcomas and in the well-differentiated regions present in 6 of 14 dedifferentiated carcinomas.
Conclusions: Loss of E-cadherin might be linked to alteration of cell morphology from epithelial to sarcomatous and undifferentiated phenotypes in carcinosarcoma and from differentiated to undifferentiated phenotypes in dedifferentiated endometrial carcinoma. The common loss of E-cadherin between the two tumors may also explain their highly aggressive clinical behavior. The mechanisms of E-cadherin loss in these tumors remain unknown, but overt cellular dyshesion in undifferentiated carcinoma and preservation of adhesion in carcinosarcoma suggest that different mechanisms underlie E-cadherin loss in these tumors.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 2:30 PM
Platform Session: Section C, Monday Afternoon