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.
Highlights
Endometrial cancer (EC) represent the sixth most common cancer in women [1]
In conclusion qRT-PCR analysis is a reliable approach to evaluate L1CAM status in endometrial carcinoma (EC) and L1CAMEXP was highly predictive for distant failure and poor outcome, confirming the large IHC-based studies
Several reports showed that immunohistochemical (IHC) detection of L1CAM in endometrial tumor samples is able to discriminate a subset of highly aggressive tumors with adverse clinical outcome [3,4,5,6] and high risk of distant recurrences [5,6]
Summary
Endometrial cancer (EC) represent the sixth most common cancer in women [1]. EC is known to be a good prognosis cancer, since it is usually detected in its early stages and survival rates are around 85% at 5 years [2]. The current challenge is to identify patients with high risk for recurrence avoiding to the others an overtreatment with its associated toxicities. In order to properly select patients candidate for adjuvant systemic treatment, it is necessary to improve the current risk assessment by the use of highly reliable biomarkers. Several reports showed that immunohistochemical (IHC) detection of L1CAM in endometrial tumor samples is able to discriminate a subset of highly aggressive tumors with adverse clinical outcome [3,4,5,6] and high risk of distant recurrences [5,6]. Management of endometrial carcinoma (EC) still needs improvement of risk assessment. L1CAM immunohistochemical (IHC) evaluation showed a unique value to predict the outcome of early EC. IHC results are often conflicting for lack of inter-laboratory standardisation
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