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04.11.2019 | Preclinical study

Phosphorylation of EphA2 receptor and vasculogenic mimicry is an indicator of poor prognosis in invasive carcinoma of the breast

verfasst von: Debarpan Mitra, Sayantan Bhattacharyya, Neyaz Alam, Sagar Sen, Saunak Mitra, Syamsundar Mandal, Shivani Vignesh, Biswanath Majumder, Nabendu Murmu

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2020

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Abstract

Purpose

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.

Methods

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.

Results

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 < 0.0001 for OS] and phospho-EphA2 (S897)-positive (HR 4.342; 95% CI 1.717–10.983; P = 0.002 for DFS and HR 5.853; 95% CI 1.663–20.602; P = 0.006 for OS) expression proved to be independent indicators of prognosis.

Conclusion

This study evaluated tumour dependency on oncogenic EphA2 receptor regulation and VM in invasive carcinoma of the breast and their prognostic significance. Significant correlations between VM, phospho-EphA2 and several clinicopathologic parameters of breast cancer were found. Subsequently, the occurrence of VM or phospho-EphA2 expression proved to be major contributors for poor prognosis in patients with breast cancer but their simultaneous expression failed to be an independent risk factor.

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Titel: Phosphorylation of EphA2 receptor and vasculogenic mimicry is an indicator of poor prognosis in invasive carcinoma of the breast
verfasst von: Debarpan Mitra
Sayantan Bhattacharyya
Neyaz Alam
Sagar Sen
Saunak Mitra
Syamsundar Mandal
Shivani Vignesh
Biswanath Majumder
Nabendu Murmu
Publikationsdatum: 04.11.2019
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2020
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05482-8

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Phosphorylation of EphA2 receptor and vasculogenic mimicry is an indicator of poor prognosis in invasive carcinoma of the breast