Background: Prostate cancer (PCa) is the second most frequent cause of cancer-related death in men worldwide. It is a heterogeneous disease at molecular and clinical levels which makes its prognosis and treatment outcome hard to predict. The epithelial-to-mesenchymal transition (EMT) marks a key step in the invasion and malignant progression of PCa. We sought to assess the co-expression of epithelial cytokeratin 8 (CK8) and mesenchymal vimentin (Vim) in locally-advanced PCa as indicators of EMT and consequently predictors of the progression status of the disease. Methods: Co-expression of CK8 and Vim was evaluated by immunofluorescence (IF) on paraffin-embedded tissue sections of 122 patients with PCa who underwent radical prostatectomies between 1998 and 2016 at the American University of Beirut Medical Center (AUBMC). EMT score was calculated accordingly and then correlated with the patients' clinicopathological parameters and PSA failure. Results: The co-expression of CK8/Vim (EMT score), was associated with increasing Gleason group. A highly significant linear association was detected wherein higher Gleason group was associated with higher mean EMT score. In addition, the median estimated biochemical recurrence-free survival for patients with < 25% EMT score was almost double that of patients with more than 25%. The validity of this score for prediction of prognosis was further demonstrated using cox regression model. Our data also confirmed that the EMT score can predict PSA failure irrespective of Gleason group, pathological stage, or surgical margins. Conclusion: This study suggests that assessment of molecular markers of EMT, particularly CK8 and Vim, in radical prostatectomy specimens, in addition to conventional clinicopathological prognostic parameters, can aid in the development of a novel system for predicting the prognosis of locally-advanced PCa.
Frontiers in oncology. 2019 Mar 11*** epublish ***
Katia A Cheaito, Hisham F Bahmad, Ola Hadadeh, Eman Saleh, Christelle Dagher, Miza Salim Hammoud, Mohammad Shahait, Zaki Abou Mrad, Samer Nassif, Ayman Tawil, Muhammad Bulbul, Raja Khauli, Wassim Wazzan, Rami Nasr, Ali Shamseddine, Sally Temraz, Marwan E El-Sabban, Albert El-Hajj, Deborah Mukherji, Wassim Abou-Kheir
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon., Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon., Division of Urology, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon., Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon.