Evaluating L1CAM expression in human endometrial cancer using qRT-PCR
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Sara Notaro1,2, Daniel Reimer1, Michaela Duggan-Peer1, Heidi Fiegl1, Annamarie Wiedermair1, Julia Rössler1, Peter Altevogt3,4, Christian Marth1, Alain Gustave Zeimet1
1Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria
2Department of Gynecology and Obstetrics, University of Brescia, Brescia, Italy
3Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
4Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
Alain Gustave Zeimet, email: firstname.lastname@example.org
Keywords: L1CAM, endometrial cancer, qRT-PCR, outcome, methylation
Received: January 04, 2016 Accepted: May 08, 2016 Published: May 24, 2016
Background: Management 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.
Methods: Here, 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.
Results: High 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.
Conclusions: In 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.
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