Prognostic significance of L1CAM expression and its association with mutant p53 expression in high-risk endometrial cancer

• DOI: 10.1038/modpathol.2015.147
• Publication Date: 2016-01-08T12:57:51Z
• Authors: Inge 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
• Keywords: L1; Clinical Significance

Studies 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 high-risk is unclear. To evaluate this, frequency, the relationship L1CAM with established biomarker p53, we analyzed expression both markers by immunohistochemistry a pilot series 116 cancers (86 endometrioid, 30 non-endometrioid subtype) features (such as high tumor grade deep myometrial invasion) correlated results clinical outcome. We used The Cancer Genome Atlas (TCGA) to validate our findings. Using previously reported cutoff 10% positive staining, 51/116 (44%) tumors were classified L1CAM-positive, no significant association between positivity rate distant metastasis (P=0.195). However, increasing threshold for 50% resulted reduction frequency L1CAM-positive 24% (28/116), (P=0.018). was strongly associated mutant p53 TCGA (P<0.001), although substantial fraction (36% morphology) p53-mutant displayed <10% positivity. Moreover, 30% p53-wild-type diffuse suggesting p53-independent mechanisms overexpression. In conclusion, proposed >10% does not predict prognosis cancer, whereas an alternative (>50%) does. strongly, but universally, may be strong enough implementation marker combination p53. suggests it also promising therapeutic target this subset.