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Prognostic significance of L1CAM expression and its association with mutant p53 expression in high-risk endometrial cancer.
- Source :
-
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2016 Feb; Vol. 29 (2), pp. 174-81. Date of Electronic Publication: 2016 Jan 08. - Publication Year :
- 2016
-
Abstract
- 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 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Carcinoma, Endometrioid mortality
Carcinoma, Endometrioid secondary
Carcinoma, Endometrioid therapy
DNA Mutational Analysis
Disease Progression
Disease-Free Survival
Endometrial Neoplasms mortality
Endometrial Neoplasms pathology
Endometrial Neoplasms therapy
Female
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Recurrence, Local
Neoplasm Staging
Phenotype
Pilot Projects
Retrospective Studies
Risk Assessment
Risk Factors
Treatment Outcome
Young Adult
Biomarkers, Tumor analysis
Biomarkers, Tumor genetics
Carcinoma, Endometrioid chemistry
Carcinoma, Endometrioid genetics
Endometrial Neoplasms chemistry
Endometrial Neoplasms genetics
Mutation
Neural Cell Adhesion Molecule L1 analysis
Tumor Suppressor Protein p53 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0285
- Volume :
- 29
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
- Publication Type :
- Academic Journal
- Accession number :
- 26743472
- Full Text :
- https://doi.org/10.1038/modpathol.2015.147