The significance of L1<scp>CAM</scp> expression in clear cell carcinoma of the endometrium

Fadare, Oluwole; Roma, Andres A.; Desouki, Mohamed Mokhtar; Gwin, Katja; Hanley, Krisztina; Jarboe, Elke A.; Liang, Sharon X.; Quick, Charles M.; Zheng, Wenxin; Parkash, Vinita; Wang, Xuan J.

doi:10.1111/his.13405

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…In our study, L1CAM expression was frequent and associated with impaired survival. Two previous studies did not find a correlation between L1CAM expression and impaired survival, possibly due to a limited sample size 16,33 . L1CAM is a transmembrane protein that is involved in increasing invasiveness, motility and metastatic potential, and has been found to be a poor prognostic factor in several cancers 34,35 .…”

Section: Discussionmentioning

confidence: 98%

“…Two previous studies did not find a correlation between L1CAM expression and impaired survival, possibly due to a limited sample size. 16 , 33 L1CAM is a transmembrane protein that is involved in increasing invasiveness, motility and metastatic potential, and has been found to be a poor prognostic factor in several cancers. 34 , 35 More recently, L1CAM positivity was found to be associated with resistance to platinum‐based chemotherapy in high‐risk EC.…”

Section: Discussionmentioning

confidence: 99%

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Pure and mixed clear cell carcinoma of the endometrium: A molecular and immunohistochemical analysis study

et al. 2023

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Background: Uterine clear cell carcinoma (CCC) consists of either pure clear cell histology but can also display other histological components (mixed uterine CCCs). In this study, the molecular and immunohistochemical background of pure and mixed uterine CCC was compared. Secondly, it was evaluated whether histological classification and molecular background affected clinical outcome. Methods: A retrospective multicenter study was performed comparing pure uterine CCCs (n = 22) and mixed uterine CCCs (n = 21). Targeted next-generation sequencing using a 12-gene targeted panel classified cases as polymerase-ε (POLE) mutated, microsatellite instable (MSI), TP53 wildtype or TP53 mutated. Immunohistochemistry was performed for estrogen receptor, progesterone receptor, L1 cell adhesion molecule, MSH6, and PMS2. Results:The following molecular subgroups were identified for pure and mixed uterine CCCs, respectively: POLE mutated 0% (0/18) and 6% (1/18); MSI in 6%(1/18) and 50% (9/18); TP53 wildtype in 56% (10/18) and 22% (4/18); TP53 mutated in 39% (7/18) and 22% (4/18) (p = 0.013). Patients with mixed CCCs had improved outcome compared to patients with pure CCCs. Frequent TP53 mutations were found in pure CCCs and frequent MSI in mixed CCCs, associated with clinical outcome. Conclusion:Pure and mixed uterine CCCs are two entities with different clinical outcomes, which could be explained by different molecular backgrounds. These results underline the relevance of both morphological and molecular evaluation, and may assist in tailoring treatment.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Pure and mixed clear cell carcinoma of the endometrium: A molecular and immunohistochemical analysis study

et al. 2023

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“…Importantly, several studies have described the association between L1CAM expression and a poor evolution of EC patients [5,30]. In particular, in early-stage EC with endometrioid histology, expression of L1CAM was related to unfavorable pathological findings, distant recurrence, and poor survival, while in high-grade EC and non-endometrioid EC, L1CAM expression was correlated to an advanced stage and lymphovascular space invasion and distant recurrence [3,31,32]. In this work, we observed that L1CAM expression in plasma samples was mainly present as free soluble and not associated with EVs, resulting in no differences between EC patients and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles-Based Biomarkers Represent a Promising Liquid Biopsy in Endometrial Cancer

Herrero

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Casas-Arozamena

et al. 2019

Cancers

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Tumor-derived extracellular vesicles (EVs) are secreted in large amounts into biological fluids of cancer patients. The analysis of EVs cargoes has been associated with patient´s outcome and response to therapy. However, current technologies for EVs isolation are tedious and low cost-efficient for routine clinical implementation. To explore the clinical value of circulating EVs analysis we attempted a proof-of-concept in endometrial cancer (EC) with ExoGAG, an easy to use and highly efficient new technology to enrich EVs. Technical performance was first evaluated using EVs secreted by Hec1A cells. Then, the clinical value of this strategy was questioned by analyzing the levels of two well-known tissue biomarkers in EC, L1 cell adhesion molecule (L1CAM) and Annexin A2 (ANXA2), in EVs purified from plasma in a cohort of 41 EC patients and 20 healthy controls. The results demonstrated the specific content of ANXA2 in the purified EVs fraction, with an accurate sensitivity and specificity for EC diagnosis. Importantly, high ANXA2 levels in circulating EVs were associated with high risk of recurrence and non-endometrioid histology suggesting a potential value as a prognostic biomarker in EC. These results also confirmed ExoGAG technology as a robust technique for the clinical implementation of circulating EVs analyses.

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“…Expression of L1CAM previously described as immunohistochemical staining of more than 10% is absent in normal endometrium [22]. In addition, expression of L1CAM is related to metastasis and poor prognosis in many cancers, including EC [17,[22][23][24][25][26][27][28]. In early-stage EC with endometrioid histology, expression of L1CAM is related to unfavorable pathological findings, distant recurrence and poor survival [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…In early-stage EC with endometrioid histology, expression of L1CAM is related to unfavorable pathological findings, distant recurrence and poor survival [22,23]. Correspondingly, in high grade EC and non-endometrioid EC (NEEC), L1CAM expression is related to unfavorable pathological findings such as advanced stage and lymphovascular space invasion (LVSI) as well as distant recurrence but not survival [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

L1CAM expression in uterine carcinosarcoma is limited to the epithelial component and may be involved in epithelial–mesenchymal transition

et al. 2018

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Uterine carcinosarcoma (UCS) has been proposed as a model for epithelial-mesenchymal transition (EMT), a process characterized by a functional change facilitating migration and metastasis in many types of cancer. L1CAM is an adhesion molecule that has been involved in EMT as a marker for mesenchymal phenotype. We examined expression of L1CAM in UCS in a cohort of 90 cases from four different centers. Slides were immunohistochemically stained for L1CAM and scored in four categories (0%, < 10%, 10-50%, and > 50%). A score of more than 10% was considered positive for L1CAM. The median age at presentation was 68.6 years, and half of the patients (53.3%) presented with FIGO stage 1 disease. Membranous L1CAM expression was positive in the epithelial component in 65.4% of cases. Remarkably, expression was negative in the mesenchymal component. In cases where both components were intermingled, expression limited to the epithelial component was confirmed by a double stain for L1CAM and keratin. Expression of L1CAM did not relate to overall or disease-free survival. Our findings suggest L1CAM is either not a marker for the mesenchymal phenotype in EMT, or UCS is not a good model for EMT.

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The significance of L1CAM expression in clear cell carcinoma of the endometrium

Cited by 5 publications

References 29 publications

Pure and mixed clear cell carcinoma of the endometrium: A molecular and immunohistochemical analysis study

Pure and mixed clear cell carcinoma of the endometrium: A molecular and immunohistochemical analysis study

Extracellular Vesicles-Based Biomarkers Represent a Promising Liquid Biopsy in Endometrial Cancer

L1CAM expression in uterine carcinosarcoma is limited to the epithelial component and may be involved in epithelial–mesenchymal transition

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