Immunohistochemical analysis of the epithelial to mesenchymal transition in uterine carcinosarcoma

Abstract

ObjectiveUterine carcinosarcoma (UCS) is a highly aggressive neoplasm that is composed of an intricate admixture of carcinomatous and sarcomatous elements. The relationship between UCS and the epithelial to mesenchymal transition (EMT) has been reported. In this study, we examined how expression of E-cadherin was associated with the expression of EMT-related proteins in UCS.MethodsUCS samples were histologically divided into three components: carcinomatous, transitional, and sarcomatous regions. Next, we examined the expression of E-cadherin and EMT-related proteins, including SNAI2, ZEB1, and TWIST1, in each component of the UCS using immunohistochemistry. The expression score was determined by combining the staining intensity and staining area of the target cells.ResultsThe expression score of E-cadherin was significantly lower in transitional and sarcomatous components than in the carcinomatous component. In addition, a significant difference in the low expression score of E-cadherin between transitional and sarcomatous components (transitional > sarcomatous components) was found. There were significant differences between the expression scores of ZEB1 in the three components (sarcomatous > transitional > carcinomatous components). However, no difference in the expression of TWIST1 between the components was found. Conversely, the expression level of SNAI2 was higher in sarcomatous or transitional components than in the carcinomatous component. However, a significant difference between the transitional and sarcomatous components was not detected.ConclusionThese results suggest that the EMT plays an essential role in the pathogenesis of UCS.

Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors

“…In addition, we noted that some tumor cells in the mesenchymal component displayed weak immunoreactivity for EMA and CK7, accompanied with a significant reduction or loss of expression of those epithelial markers in the adjacent epithelial component. Given the fact that uterine conventional carcinosarcoma is currently considered as a metaplastic high-grade endometrial carcinoma [57,58], our findings raise the possibility that MLCS may be also a metaplastic MLA in which the mesenchymal component retains at least partially the morphological and/or immunohistochemical features of MLA (i.e., the mesenchymal morphology of MLCS may represent a result of epithelial-mesenchymal transition or transdifferentiation of MLA). Further studies are necessary to investigate whether uterine MLCS shows similar immunohistochemical and molecular features to those of MLA and to confirm the monoclonal origin of uterine MLCS.…”

Lineage Plasticity in Cancer: The Tale of a Skin-Walker

“…When categorized into carcinomatous, transitional and sarcomatous regions, it was observed that the sarcomatous region of tissues showed higher EMT expression markers, namely ZEB1 and SNAI2, as compared to the carcinomatous region. Moreover, the level of ZEB1 was higher in the sarcomatous region when compared to the transitional region [ 93 ]. Similar to UCS, ovarian carcinosarcoma (OCS) showed enriched expression of EMT markers when compared to the cohort of high-grade serous carcinoma in TCGA [ 87 ], suggesting that OCS indicates phenotypic and/or lineage plasticity signatures through the EMT landscape.…”

Lineage Plasticity in Cancer: The Tale of a Skin-walker

“…The tissue was categorized into carcinomatous, transitional and sarcomatous regions and it was observed that the sarcomatous region showed higher EMT expression markers, namely ZEB1 and SNAI2 when compared to the carcinomatous region. Also, the level of ZEB1 was higher in the sarcomatous region when compared to the transitional region [93]. Similar to UCS, ovarian carcinosarcoma (OCS) showed enriched expression of EMT markers when compared to the cohort of high-grade serous carcinoma in TCGA [87] suggesting that OCS indicates phenotypic and/or lineage plasticity signatures through the EMT landscape.…”