Pathology – Research and Practice 209 (2013) 418–423 Contents lists available at SciVerse ScienceDirect Pathology – Research and Practice jo u r n al hom epage: www.elsevier.com/l ocate/prp Original article Beclin 1 and bcl-2 expressions in bladder urothelial tumors and their association with clinicopathological parameters Sirin Baspinar a,∗ , Sema Bircan a , Gulcan Yavuz b , Nilgun Kapucuoglu a a Department of Pathology, Suleyman Demirel University, School of Medicine, Isparta, Turkey b Department of Pathology, Artvin State Hospital, Artvin, Turkey a r t i c l e i n f o Article history: Received 26 January 2013 Received in revised form 27 March 2013 Accepted 16 April 2013 Keywords: Beclin 1 Bcl-2 Bladder urothelial tumor a b s t r a c t Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation, as well as in the development and progression of cancer. The aim of this study was to examine the expression of beclin 1 and bcl-2 in bladder urothelial tumors, and to investigate the relationship between these two markers and clinicopathological parameters. Our study included 84 bladder urothelial tumors and 10 non-tumoral bladder tissues. Immunohistochemistry was performed on tissue microarray (TMA) sections and was evaluated semiquantitatively on the basis of the percentage of positively stained cells (proportion) and staining intensity. A significant association was found between the expression score of beclin 1 and pT stages of the urothelial tumors (p = 0.012). Also, the level of beclin 1 expression inversely correlated with histological grade and pT stages (p = 0.009, r = -0.284; p = 0.001, r = -0.361, respectively). The bcl- 2 expression level positively correlated with histological grade and pT stages of the urothelial tumors (p = 0.026, r = 0.243; p < 0.0001, r = 0.491, respectively). In addition, the level of beclin 1 expression tended to be inversely correlated with the bcl-2 expression level in urothelial tumors (p = 0.055, r = -0.210). According to our data, down-regulation of beclin 1 expression and also bcl-2 overexpression seem to play an important role in the progression and aggressiveness of bladder urothelial tumors. © 2013 Elsevier GmbH. All rights reserved. Introduction Bladder urothelial carcinoma (BUC) is the second most com- mon malignancy of the genito-urinary tract [1]. Similarly, in most developing countries, BUC is the second most common malignancy in Turkey [2]. It takes the seventh place as a cause of cancer-related deaths in our country, and the incidence of BUC increases with age [2]. Although pathological grade and clinical stage have been con- sidered significant indicators for predicting the outcome of bladder cancer, it is difficult to predict an accurate prognosis with any sin- gle factor. Therefore, studies currently focus on protein and genetic markers, as more reliable prognostic factors are needed [3]. Accord- ing to the current belief, bladder cancer development is a multi-step process in which genetic and environmental factors also several oncogenes, tumor suppressor genes, cell cycle regulators, as well as disturbances in apoptotic cell death regulation are involved [4]. Apoptosis and autophagy are biological processes that play a central role in tissue homeostasis, development, disease, and espe- cially in the oncogenesis of mammals [5]. Apoptosis is defined as suicidal cell death which is one of the important mechanisms ∗ Corresponding author at: Suleyman Demirel Universitesi, Tıp Fakultesi, Tıbbi Patoloji AD, Isparta, Turkey. Tel.: +90 246 2119290; fax: +90 246 2371762. E-mail address: sirinbaspinar@gmail.com (S. Baspinar). needed to maintain a stable internal environment [6]. Autophagy at a basal level is an important process regulating the balance between synthesis and degradation of cellular constituents, and plays an important role in cellular homeostasis by degrading exces- sive, damaged, and/or aged proteins and organelles [5]. Defective autophagy has also been implicated in the pathogenesis of a vari- ety of diseases, including neurodegenerative diseases, autoimmune diseases, malignancies, infection, and muscle cell dysfunction [7]. It has been reported that autophagy may play an important role in the regulation of cancer development and progression [8]. Possible molecular mechanisms for crosstalk between autophagy and apoptosis have been suggested [9]. The crosstalk between the autophagy and apoptosis signaling pathways is critical to the overall fate of the cell depending on the nature of the stimulus and the actual metabolic status of the cell, thus autophagy can suppress or enable apoptosis [10]. Beclin 1, the mammalian ortholog of yeast Atg6/Vps30, origi- nally discovered in a yeast two hybrid screen as a bcl-2-interacting protein, is an important mediator of autophagy [8]. Bcl-2 family members functioning as oncogenic and anti-death molecules modulate various homeostatic, developmental, and disease pro- cesses, and the antiapoptotic protein bcl-2 binds to beclin 1 under non-stress conditions and inhibits autophagy [9,11]. Beclin 1 expression promotes autophagy, and suppression of its expres- sion sensitizes the cells to starvation-induced apoptosis. Indeed, 0344-0338/$ – see front matter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.prp.2013.04.006