Oncotarget

Research Papers:

Evaluating L1CAM expression in human endometrial cancer using qRT-PCR

Sara Notaro _, Daniel Reimer, Michaela Duggan-Peer, Heidi Fiegl, Annamarie Wiedermair, Julia Rössler, Peter Altevogt, Christian Marth and Alain Gustave Zeimet

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Oncotarget. 2016; 7:40221-40232. https://doi.org/10.18632/oncotarget.9574

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Abstract

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

Correspondence to:

Alain Gustave Zeimet, email: alain.zeimet@uki.at

Keywords: L1CAM, endometrial cancer, qRT-PCR, outcome, methylation

Received: January 04, 2016    Accepted: May 08, 2016    Published: May 24, 2016

ABSTRACT

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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