L1CAM expression in uterine carcinosarcoma is limited to the epithelial component and may be involved in epithelial–mesenchymal transition

Abstract

Uterine carcinosarcoma (UCS) has been proposed as a model for epithelial-mesenchymal transition (EMT), a process characterized by a functional change facilitating migration and metastasis in many types of cancer. L1CAM is an adhesion molecule that has been involved in EMT as a marker for mesenchymal phenotype. We examined expression of L1CAM in UCS in a cohort of 90 cases from four different centers. Slides were immunohistochemically stained for L1CAM and scored in four categories (0%, < 10%, 10-50%, and > 50%). A score of more than 10% was considered positive for L1CAM. The median age at presentation was 68.6 years, and half of the patients (53.3%) presented with FIGO stage 1 disease. Membranous L1CAM expression was positive in the epithelial component in 65.4% of cases. Remarkably, expression was negative in the mesenchymal component. In cases where both components were intermingled, expression limited to the epithelial component was confirmed by a double stain for L1CAM and keratin. Expression of L1CAM did not relate to overall or disease-free survival. Our findings suggest L1CAM is either not a marker for the mesenchymal phenotype in EMT, or UCS is not a good model for EMT.

Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition

“…It is intriguing to speculate that Fbxw7 -mutant endometrioid adenocarcinomas (were they left in the body) might have a propensity to progress into UCS, perhaps through the acquisition of Tp53 mutations. This is further suggested by the fact that UCSs are more likely to harbor p53 mutations, and our finding that Fbxw7 -mutant endometrioid adenocarcinomas are more likely to express L1CAM, a marker of EMT (59) frequently overexpressed in UCS (58). However, further investigations will be required to better define the natural history, precursors, and histologic intermediates for UCS.…”

“…We studied 28 cases harboring canonical Fbxw7 mutations (WD40 hotspot or definite null mutations) and 20 cases without Fbxw7 single nucleotide variants leading to amino acid alterations ( SI Appendix , Table S3). All cases were subjected to IHC for L1CAM, a well-established marker for EMT in human ECs (58, 59). Notably, only Fbxw7-mutant tumors expressed L1CAM, and all of these were also p53-positive by IHC, although not all p53-positive cases harbored Fbxw7 mutations ( SI Appendix , Fig.…”

Clinical significance and biological role of L1 cell adhesion molecule in gastric cancer

“…Identification of patients at high risk for lymph node and distant metastasis could help oncologists with treatment decision-making and improve prognosis of GC. Recent evidence has demonstrated L1CAM as an oncogenic driver in various malignancies, 23 – 27 and the clinical burden and prognostic biomarker potential of L1CAM expression evaluated by immunohistochemistry has been shown in several cancers, including GC. However, to date, no study has shown that L1CAM can be used for preoperative prediction of risk for recurrence, lymph node metastasis and distant metastasis.…”

Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma

“…In contrast, although the expression of L1CAM is a strong predictor of poor outcome in endometrial cancer and overexpression of L1CAM has been related to EMT in endometrial cancer cell lines [88], in clinical samples of ECS, only the epithelial component was positive in 65% of the cases, while no expression was seen in the mesenchymal part. Thus in ECS, L1CAM is not a marker for the mesenchymal phenotype [89].…”