EGFR as a stable marker of prostate cancer dissemination to bones
Menée à l'aide d'échantillons tumoraux prélevés sur 1 039 patients atteints d'un cancer de la prostate, de cellules tumorales circulantes issues de 39 patients présentant un risque élevé de récidive et d'échantillons de métastases provenant de 21 patients atteints d'un cancer de la prostate résistant à la castration, cette étude démontre que le récepteur EGFR est un marqueur stable de la dissémination des cellules cancéreuses vers les os
Background : Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains incurable. Therefore, there is a need for markers indicating metastatic dissemination.
Methods : EGFR overexpression (EGFRover) was tracked in 1039 primary tumours, circulating tumour cells from 39 d’Amico high-risk patients and metastatic samples from 21 castration-resistant PCa cases. EGFR status was compared to clinical parameters and multiple molecular factors were assessed using immunohistochemistry and gene ontology analysis. The functional aspect of EGFR was evaluated by plating PC-3 cells on soft and rigid matrices.
Results : EGFRover was found in 14% of primary tumours, where it was associated with shorter metastasis-free survival and was an independent indicator of worse overall survival. EGFRover correlated with a pro-migratory and pro-metastatic phenotype of tumour cells as well as rich collagen fibre content. All circulating tumour cells (detected in 13% of cases) were positive for EGFR, independent of their EMT-related phenotype. EGFRover was more prevalent in castration-resistant bone metastases (29% of patients) and supported growth of human PCa cells on rigid matrices mimicking bone stiffness.
Conclusions : EGFRover is a stable, EMT-independent marker of PCa disseminating to rigid organs, preferentially bones.
British Journal of Cancer , résumé, 2020