L1 cell adhesion molecule (L1CAM) expression in endometrial cancer is associated with SRC pathway activation with potential for targeted therapy with dasatinib

2021 ◽  
Vol 162 ◽  
pp. S195
Author(s):  
Jordan Mattson ◽  
Jinhua Wang ◽  
Sabrina Bedell ◽  
Mihae Song ◽  
James Richter ◽  
...  
2020 ◽  
Vol 8 (A) ◽  
pp. 113-118
Author(s):  
Aya Magdy Elyamany ◽  
Solafa Amin Abd-ElAziz ◽  
Samar A. Elsheikh ◽  
Somia A. M. Soliman

BACKGROUND: Endometrial cancer is the most common cancer of the female genital tract. No effective biomarkers currently exist to allow for an efficient risk classification of endometrial carcinoma or to direct treatment (adjuvant radiation and/or chemotherapy) or to triage pelvic and para-aortic lymphadenectomy. L1 cell adhesion molecule (L1CAM) a transmembrane protein of the immunoglobulin family that has been implicated in promoting tumor cell proliferation, migration, invasion, and metastasis became an attractive candidate as a potential biomarker in endometrial carcinoma and potential therapeutic target in high-risk groups. OBJECTIVES: Evaluation of L1CAM expression in endometrial carcinoma and correlation of this expression with various pathological parameters. MATERIALS AND METHODS: Immunohistochemical staining for L1CAM was performed on paraffin-embedded sections of 80 cases of endometrial carcinomas that underwent total hysterectomy with bilateral salpingo-oophorectomy. Expression of L1CAM in >10% of tumor cells was interpreted as positive. RESULTS: L1CAM expression was detected in 22.5% of cases and showed statistically significant correlation with non-endometrioid histological type, high grade, high FIGO stage, high pathological (T) stage, cervical involvement, nodal metastasis, lymphovascular space invasion, and high-risk tumor according to the European Society for Medical Oncology system for risk stratification (p < 0.05). CONCLUSION: The high rate of L1CAM expression in high-risk endometrial carcinomas suggests that L1CAM represents a potential marker for the identification of patients needing closer follow-up and aggressive treatment. In addition, its potential role as a therapeutic target for high-risk endometrial cancer seems promising.


2016 ◽  
Vol 26 (8) ◽  
pp. 1465-1471 ◽  
Author(s):  
Annukka Pasanen ◽  
Taru Tuomi ◽  
Jorma Isola ◽  
Synnöve Staff ◽  
Ralf Bützow ◽  
...  

ObjectiveThe aim was to study the association of L1 cell adhesion molecule (L1CAM) expression with the outcome of patients with endometrial cancer, especially with regard to conventional risk variables, and to compare the patterns of relapse in L1CAM-positive and -negative cancers.MethodsThis was a retrospective study of 805 women. The Kaplan–Meier method and univariate and multivariate Cox regression models were applied for survival analyses. Missing data were replaced using multiple imputation. The median follow-up time was 51 months (range, 1–98).ResultsOne hundred twenty-one (15.0%) cases were L1CAM positive. L1CAM positivity was associated with high stage (I vs II–IV) (odds ratio [OR], 2.3), lymph node involvement (OR, 2.9), poor differentiation (OR, 6.1), non-endometrioid histology (OR, 9.9), lymphovascular space invasion (OR, 2.8), cervical stromal invasion (OR, 1.8), positive peritoneal cytology (OR, 4.1), and age older than 65 years (OR, 2.8). The frequencies of deep myometrial invasion (50% or deeper), tumor size 2 cm or greater, and body mass index 30 kg/m2 or greater were not significantly different between L1CAM-positive and -negative cases. L1CAM predicted poor disease-specific survival in endometrioid (P < 0.0001) but not in non-endometrioid carcinomas (P = 0.934). The negative impact of L1CAM on outcome was confirmed in a Cox multivariate disease-specific survival analysis. Univariate survival analyses in the different ESMO–ESGO–ESTRO endometrial cancer risk groups showed an association between L1CAM positivity and poor outcome in intermediate (hazard ratio, 12) and high-risk advanced metastatic (hazard ratio, 2.0) groups. Extra-abdominal relapses were more frequent in L1CAM-positive (13.2%) than L1CAM-negative (1.9%) stage I endometrioid carcinomas (P < 0.0001), whereas other site-specific relapses in local cancers were L1CAM independent.ConclusionsL1CAM is associated with the occurrence of poor prognostic variables and predicts advanced disease in endometrial cancer. L1CAM predicts extra-abdominal relapses and poor survival in endometrioid endometrial cancer, but seems not to be a prognostic factor in non-endometrioid carcinomas.


PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0209294 ◽  
Author(s):  
Daniela de Freitas ◽  
Fernando Nalesso Aguiar ◽  
Cristina Anton ◽  
Carlos Eduardo Bacchi ◽  
Jesus Paula Carvalho ◽  
...  

2019 ◽  
Vol 121 (12) ◽  
pp. 1058-1068 ◽  
Author(s):  
Takashi Ichikawa ◽  
Yoshinaga Okugawa ◽  
Yuji Toiyama ◽  
Koji Tanaka ◽  
Chengzeng Yin ◽  
...  

Abstract Background L1 cell adhesion molecule (L1CAM) is highly expressed in malignant tumours and might play a pivotal role in tumour progression. Methods We analysed by immunohistochemistry L1CAM protein expression in formalin-fixed, paraffin-embedded specimens from 309 GC patients. We performed propensity score matching (PSM) analysis to clarify the prognostic impact of L1CAM in GC patients. We evaluated L1CAM gene expression in fresh frozen specimens from another group of 131 GC patients to establish its clinical relevance. The effects of changes in L1CAM were investigated in vitro and in vivo. Results L1CAM was mainly expressed in tumour cells of GC tissues. Elevated L1CAM expression was an independent prognostic factor for overall and disease-free survival, and an independent risk factor for distant metastasis in GC patients. PSM analysis showed that high L1CAM expression was significantly associated with poor prognosis. L1CAM gene expression using fresh frozen specimens successfully validated all of these findings in an independent cohort. Inhibition of L1CAM suppressed cell proliferation, cycle progress, invasion, migration and anoikis resistance in GC cells. Furthermore, L1CAM inhibition suppressed the growth of peritoneal metastasis. Conclusion L1CAM may serve as a feasible biomarker for identification of patients who have a high risk of recurrence of GC.


2007 ◽  
Vol 27 (36) ◽  
pp. 9653-9663 ◽  
Author(s):  
M. A. Wolman ◽  
A. M. Regnery ◽  
T. Becker ◽  
C. G. Becker ◽  
M. C. Halloran

Sign in / Sign up

Export Citation Format

Share Document