Different expression patterns of KIT, EGFR, and HER-2 (c-erbB-2) oncoproteins between epithelial and mesenchymal...

Uterine carcinosarcoma histologically comprises the components of epithelial and mesenchymal malignancies, and is known to be clinically highly aggressive. To reveal the significance of the expression of tyrosine-kinase-receptor-type oncoproteins in this tumor type, the incidence and distribution of the KIT, EGFR, and HER-2 (c-erbB-2) oncoproteins were immunohistochemically examined in 16 surgically resected cases. For 6 cases, the EGFR and HER-2 amplifications were also examined by fluorescence in situ hybridization (FISH). In the epithelial component, overexpressions of KIT, EGFR, and HER-2 were detected in 4 (25%), 5 (31%), and 9 (56%) cases, respectively, whereas these overexpressions in the mesenchymal component were detected in 6 (38%), 8 (50%), and 1 (6%) cases, respectively. KIT and EGFR were co-overexpressed in the mesenchymal component of 4 cases and in the epithelial component of 2 cases. However, HER-2 overexpression was mostly detected in the epithelial component only, and tended to occur independently of KIT and/or EGFR overexpression. By FISH, one of the 4 cases with HER-2 overexpression showed low-level gene amplification. In two cases with EGFR overexpression, the gain of EGFR alleles and/or polyploidization of chromosome 7 had occurred. The expression patterns of KIT, EGFR, and HER-2 differed between the epithelial and mesenchymal components, and the regulation of their expression appeared important in the acquisition of mesenchymal metaplasia in uterine carcinosarcoma. Structural and/or numerical alterations of chromosomes might be in part involved in EGFR and/or HER-2 overexpression in this tumor type.