Ontology type: schema:ScholarlyArticle Open Access: True
2016-02
AUTHORSInge C Van Gool, Ellen Stelloo, Remi A Nout, Hans W Nijman, Richard J Edmondson, David N Church, Helen J MacKay, Alexandra Leary, Melanie E Powell, Linda Mileshkin, Carien L Creutzberg, Vincent T H B M Smit, Tjalling Bosse
ABSTRACTStudies in early-stage, predominantly low- and intermediate-risk endometrial cancer have demonstrated that L1 cell adhesion molecule (L1CAM) overexpression identifies patients at increased risk of recurrence, yet its prognostic significance in high-risk endometrial cancer is unclear. To evaluate this, its frequency, and the relationship of L1CAM with the established endometrial cancer biomarker p53, we analyzed the expression of both markers by immunohistochemistry in a pilot series of 116 endometrial cancers (86 endometrioid, 30 non-endometrioid subtype) with high-risk features (such as high tumor grade and deep myometrial invasion) and correlated results with clinical outcome. We used The Cancer Genome Atlas (TCGA) endometrial cancer series to validate our findings. Using the previously reported cutoff of 10% positive staining, 51/116 (44%) tumors were classified as L1CAM-positive, with no significant association between L1CAM positivity and the rate of distant metastasis (P=0.195). However, increasing the threshold for L1CAM positivity to 50% resulted in a reduction of the frequency of L1CAM-positive tumors to 24% (28/116), and a significant association with the rate of distant metastasis (P=0.018). L1CAM expression was strongly associated with mutant p53 in the high-risk and TCGA series (P<0.001), although a substantial fraction (36% of endometrioid, 10% of non-endometrioid morphology) of p53-mutant endometrial cancers displayed <10% L1CAM positivity. Moreover, 30% of p53-wild-type non-endometrioid endometrial cancers demonstrated diffuse L1CAM staining, suggesting p53-independent mechanisms of L1CAM overexpression. In conclusion, the previously proposed threshold for L1CAM positivity of >10% does not predict prognosis in high-risk endometrial cancer, whereas an alternative threshold (>50%) does. L1CAM expression is strongly, but not universally, associated with mutant p53, and may be strong enough for clinical implementation as prognostic marker in combination with p53. The high frequency of L1CAM expression in high-risk endometrial cancers suggests that it may also be a promising therapeutic target in this tumor subset. More... »
PAGES174-181
http://scigraph.springernature.com/pub.10.1038/modpathol.2015.147
DOIhttp://dx.doi.org/10.1038/modpathol.2015.147
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1007170292
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/26743472
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]Download the RDF metadata as:Â json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/modpathol.2015.147'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/modpathol.2015.147'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/modpathol.2015.147'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/modpathol.2015.147'
This table displays all metadata directly associated to this object as RDF triples.
390 TRIPLES
21 PREDICATES
87 URIs
50 LITERALS
38 BLANK NODES