Phosphorylation of EphA2 receptor and vasculogenic mimicry is an indicator of poor prognosis in invasive carcinoma of the breast
| Autor: | Shivani Vignesh, Nabendu Murmu, Debarpan Mitra, Sayantan Bhattacharyya, Neyaz Alam, Biswanath Majumder, Sagar Sen, Saunak Mitra, Syamsundar Mandal |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Gene Expression Breast Neoplasms Triple Negative Breast Neoplasms Kaplan-Meier Estimate 03 medical and health sciences 0302 clinical medicine Breast cancer Cell Line Tumor Internal medicine Biomarkers Tumor medicine Humans Vasculogenic mimicry Phosphorylation Risk factor Survival analysis Aged Neoplasm Staging Proportional Hazards Models Neovascularization Pathologic business.industry Receptor EphA2 Hazard ratio Middle Aged Prognosis medicine.disease Immunohistochemistry 030104 developmental biology 030220 oncology & carcinogenesis Cohort Nottingham Prognostic Index Female business |
| Zdroj: | Breast Cancer Research and Treatment. 179:359-370 |
| ISSN: | 1573-7217 0167-6806 |
| Popis: | The occurrence of vasculogenic mimicry (VM) and EphA2-mediated tumour progression are associated with poor prognosis in various solid tumours. Here, we aimed to investigate the prognostic implications of VM and its association with phosphorylated EphA2 receptor in invasive carcinoma of the breast. The patients were stratified based on CD-31/PAS dual staining and subsequently the expression status of phospho-EphA2 (S897), FAK, phospho-ERK1/2 and Laminin 5Ƴ2 was analysed by immunohistochemistry. Survival of patients was correlated within the stratified cohort. The pathologically defined VM phenotype and phospho-EphA2 (S897) expression status were significantly associated with lower disease-free survival (DFS) and overall survival (OS). Both the features were also found to be significantly associated with higher nodal status, poor Nottingham Prognostic Index (NPI) and were more prevalent in the triple-negative breast cancer (TNBC) group. Incidentally, there were no significant association between age of the patient, grade and size of the tumour with VM and phospho-EphA2 (S897). The effector molecules of phospho-EphA2 (S897) viz., Focal Adhesion Kinase (FAK), phospho-ERK1/2 and Laminin 5Ƴ2 were significantly upregulated in the VM-positive cohort. Survival analysis revealed that the VM and phospho-EphA2 (S897) dual-positive cohort had poorest DFS [mean time = 48.313 (39.992–56.633) months] and OS [mean time = 56.692 (49.055–64.328) months]. Individually, VM-positive [Hazard Ratio (HR) 6.005; 95% confidence interval (CI) 2.002–18.018; P = 0.001 for DFS and HR 11.654; 95% CI 3.195–42.508; P |
| Databáze: | OpenAIRE |
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