Evaluating L1CAM expression in human endometrial cancer using qRT-PCR
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. Meth...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
May 24, 2016
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| In: |
OncoTarget
Year: 2016, Jahrgang: 7, Heft: 26, Pages: 40221-40232 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.9574 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.18632/oncotarget.9574 Verlag, Volltext: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=9574&path[]=29971 
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| Verfasserangaben: | Sara Notaro, Daniel Reimer, Michaela Duggan-Peer, Heidi Fiegl, Annamarie Wiedermair, Julia Rössler, Peter Altevogt, Christian Marth, Alain Gustave Zeimet |
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| 520 | |a 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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