Ebp1 expression in benign and malignant prostate.
BACKGROUND
ErbB3-binding protein 1 (Ebp1) is a member of the PA2G4 family of proliferation-regulated proteins that is expressed in multiple malignant and non-malignant cells. ErbB3 and other members of the EGFR family have been implicated in cancer progression, it however remains unknown whether Ebp1 participate in prostate cancer progression in vivo. Therefore, the present study examines Ebp1 expression in cancerous and non-cancerous prostates tissues. Ebp1 expression was also correlated to known Ebp1 regulated proteins (Androgen receptor (AR), Cyclin D1 & ErbB3) and the proliferation marker Ki67. Furthermore we evaluated whether Ebp1 expression correlated with biochemical recurrence (BCR) following radical prostatectomy.


METHODS
The expression of Ebp1, AR, Cyclin D1, ErbB3 and Ki67 were evaluated by immunohistochemistry using three separate tissue micro-arrays containing normal prostate tissues, non-cancerous tissue adjacent to the primary tumor, hormone-sensitive and hormone-refractory cancerous tissues. Multivariate COX regression analysis was performed with four clinical parameters in order to correlate Ebp1 expression with PCa progression.


RESULTS
The expression of Ebp1 significantly increased with the progression from normal to hormone sensitive and to hormone refractory PCa. Furthermore, we observed strong correlation between Ebp1 expression and the nuclear expression of AR, Cyclin D1 and ErbB3 in both normal adjacent and cancer tissues. The expression of AR, Cyclin D1 and ErbB3 in normal adjacent tissues correlated with PSA relapse, whereas Ebp1 on its own did not significantly predict PSA relapse. Finally, in a multivariate analysis with a base clinical model (Gleason, Pre-op PSA, surgical margins and P-stage) we identified the multi-marker combination of Ebp1+/Cyclin D1- as an independent predictor of PSA relapse with a hazard ratio of 4.79.


CONCLUSIONS
Although not related to disease recurrence, this is the first in vivo study to report that Ebp1 expression correlates with PCa progression.
Gannon
Philippe O
PO
Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal. 1560 rue Sherbrooke East, Montreal, Quebec, Canada.
Koumakpayi
Ismaël Hervé
IH
Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal. 1560 rue Sherbrooke East, Montreal, Quebec, Canada.
Le Page
Cécile
C
Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal. 1560 rue Sherbrooke East, Montreal, Quebec, Canada.
Karakiewicz
Pierre I
PI
Cancer Prognostics and Health Outcomes Unit & Department of Surgery, Hôpital St-Luc (CHUM), 1058 rue St-Denis, Montreal, Quebec, Canada.
Mes-Masson
Anne-Marie
AM
Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal. 1560 rue Sherbrooke East, Montreal, Quebec, Canada.|Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Saad
Fred
F
Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal. 1560 rue Sherbrooke East, Montreal, Quebec, Canada.|Cancer Prognostics and Health Outcomes Unit & Department of Surgery, Hôpital St-Luc (CHUM), 1058 rue St-Denis, Montreal, Quebec, Canada.|Department of Surgery, CHUM, Université de Montréal, Montreal, Quebec, Canada.