Evaluating L1CAM expression in human endometrial cancer using qRT-PCR

Abstract

BackgroundManagement of endometrial carcinoma (EC) still needs improvement of risk assessment. Recently, L1CAM immunohistochemical (IHC) evaluation showed a unique value to predict the outcome of early EC. However IHC results are often conflicting for lack of inter-laboratory standardisation.MethodsHere, as a proof of concept and to increase reproducibility we assayed eighty-two EC and 26 normal endometrium samples for L1CAM expression (L1CAMEXP) via qRT-PCR. The IHC evaluation was performed in 50 cancer samples. Moreover, we aimed to substantiate the in-vitro findings of L1CAM regulation through its promoter methylation (L1CAMMET), miR-34a expression and miR-34a promoter methylation. DNA methylation was assessed with MethyLight PCR technique.ResultsHigh overall concordant results between IHC and RT-PCR evaluations were found. L1CAMEXP was detected in 11% of cancer specimens. These positive cancers exhibited a worse DFS (p=0.032) and OS (p=0.016) in a multivariate COX-regression model. L1CAMEXP predicted distant failure (p=0.007) and L1CAMMET predicted risk-reduction of lymph-node involvement (p=0.005). Inverse correlations between L1CAMEXP and L1CAMMET (p=0.004) and between L1CAMEXP and miR-34a expression (p=0.002) were found.ConclusionsIn conclusion qRT-PCR analysis is a reliable approach to evaluate L1CAM status in EC and L1CAMEXP was highly predictive for distant failure and poor outcome, confirming the large IHC-based studies. Interestingly, L1CAMMET was able to assess the risk of pelvic lymph-node involvement. Especially the latter finding has to be confirmed in larger prospective series.

L1CAM promotes epithelial to mesenchymal transition and formation of cancer initiating cells in human endometrial cancer

“…L1CAM functions mostly in proliferation, migration, invasion, and survival through L1CAM homophilic interaction or heterophilic interactions with other cell adhesion molecules, integrins, or growth factor receptor, while the cellular properties are not homogeneous among different types of cancers ( 12 ). Recently, it has been reported that L1CAM was involved in progression of endometrial cancer ( 13 ).…”

Prognostic significance of L1 cell adhesion molecule in cancer patients: A systematic review and meta-analysis

“…Thirty studies [ 5 – 8 , 12 , 14 , 15 , 17 – 25 , 27 , 28 , 30 – 37 , 39 – 41 , 43 ] with data from 7743 patients were available to evaluate the effect of L1CAM expression on OS. The random-effects model was applied to calculate the pooled HR and 95%CI because of the significant heterogeneity among studies (I 2 =81.8%, P<0.01).…”

A Targeted Mass Spectrometry Strategy for Developing Proteomic Biomarkers: A Case Study of Epithelial Ovarian Cancer

“…THBS1 is an endogenous angiogenesis inhibitor which has previously been associated with the development of tumor microenvironment and angiogenesis and has been shown to promote migration of cancer cells (60 -62). L1CAM is a cell adhesion molecule, which was originally identified as a neural cell adhesion molecule in the central nervous system (63), but L1CAM expression has been identified in a variety of tumor types (64) and has been recently reported the be involved in the progression of endometrial cancer (65). Lastly, IGHG2 forms the constant region of immunoglobulin heavy chains.…”