The Combined Role of EN2, CD73 and KI67 in Predicting Recurrence and Progression of Non-muscle Invasive Bladder Cancer

Abstract

Objectives: The survival rate for the most of patients with non- muscle invasive bladder cancer (NMIBC) is favorable; however, the rates of recurrence and progression to muscle invasive bladder cancer (MIBC) are the major principles of long- term outcome. There is an essential need to find a panel of markers to predict tumor recurrence and progression to be used in regular clinical practice and treat the disease appropriately. Therefore, we investigated in this study, the immunohistochemical expression of EN2, CD73, p63 and Ki-67 in NMIBC in order to evaluate the ability of this panel of markers to predict tumor recurrence and progression. Methods: In all, 122 patients diagnosed with NMI transitional cell carcinoma of the bladder in a Urology and Pathology Department from January 2014 to December 2016, were included in the study. Paraffin-embedded specimens were obtained by transurethral resection of the bladder tumors. After grading and staging of the sections stained with haematoxylin and eosin, they were evaluated using EN2, CD73 p63 and KI67 immunohistochemical staining before and after immunotherapy with bacille Calmette-Guerin (BCG), and patients were followed up for 3 years. Results: High CD73 expression is significantly associated with lower stage (p= 0.01) and lower grade (p= 0.02). There was no significant relationship between EN2, p63 and KI67 expression and tumor staging or grading. There was a significant relation between EN2, Ki67 positivity and CD73 negativity with recurrence, progression and death of the studied cases. Conclusions: Patients with TCC who are selected for BCG treatment should preferably be positively immunoreactive for CD73 but negative for both EN2 and Ki67. These patients are likely to be less susceptible to recurrence and/or progression after BCG adjuvant therapy. On the other hand different immunological profile necessitates closer follow up for early detection of tumor recurrence and progression.