ORIGINAL ARTICLE Cell Cycle Markers in the Evaluation of Bladder Cancer Jéssica Niederauer Leote da Silva 1 & Alana Durayski Ranzi 1 & Caroline Trainotti Carvalho 1 & Tales Vicente Scheide 1 & Yuri Thomé Machado Strey 1 & Túlio Meyer Graziottin 1,2 & Claudia Giuliano Bica 1 Received: 1 March 2016 /Accepted: 8 February 2018 # Arányi Lajos Foundation 2018 Abstract Bladder cancer (BC) is a heterogeneous neoplasia characterized by a high number of recurrences. Standardized clinical and morphological parameters are not always sufficient to predict individual tumor behavior. The aim of this study was to evaluate the expression of cell cycle regulators proteins as potential adjuvant in prognosis and monitoring of this disease. Block paraffin samples from patients with urothelial bladder carcinoma treated by transurethral resection (TUR) were collected to immunohis- tochemistry analysis for proteins p16, p21, p27, p53, pRb and Ki-67. Chisquare, logistic regression and Kaplan-Meier curve were used to analyze the prognostic value of these markers. Of the 93 patients included in the study, the main categories of staging observed were T1 (53%) and Ta (29%), and the distribution between tumor grades was 58% of patients with low grade to 42% of patients with high grade. The expressions of p16, p21, p27, p53, pRb and Ki-67 were altered in 31%, 42%, 60%, 91%, 27% and 56% of patients, respectively. The immunohistochemical expression of Ki-67 was associated with tumor histological grade (p = 0.016), and expression of pRb with recurrence-free survival (p = 0.035), but no isolated marker was significant associated with recurrence and progression in multivariate analysis. More than two markers abnormally expressed were associated with presence of recurrence (p = 0.005) and lower recurrence-free surviva (p = 0.004). Our panel marker has important prognostic value for BC, especially when more than two have altered expression predicting good clinical recurrence implication. Keywords Bladder cancer . Cell cycle markers . Prognosis . Immunohistochemistry Introduction Bladder cancer (BC) is a heterogeneous disease strongly as- sociated with smoking. It is the most frequent urinary tract neoplasia, with approximately 430,000 new cases diagnosed in 2012 [1, 2]. Ninety percent of BC are urothelial carcinomas, classified according to TNM staging as non-muscle-invasive (Ta, Tcis, T1) or muscle-invasive (T2, T3, T4) [3, 4]. The majority of BC (75%) are non-muscle-invasive cancers. These tumours can recidivate in 60%–70% and progress in 20%–30% of cases [5, 6]. Cystoscopy, urinary cytology and transurethral resection (TUR) are utilized to establish diagnosis and follow-up in BC [6, 7]. Histological grade and TNM staging are important prognostic factors for aggressiveness in BC [6]. However, due to BC heterogeneity, there is no definitive parameter to predict the behaviour and prognosis of BC [8, 9]. For this reason, several markers have been investigated to complement standard cytopathology and histopathological examination. Cell cycle and proliferation proteins have been * Claudia Giuliano Bica claudia@ufcspa.edu.br Jéssica Niederauer Leote da Silva jess.niederauer@gmail.com Alana Durayski Ranzi alana_ranzi@hotmail.com Caroline Trainotti Carvalho trainottic@yahoo.com.br Tales Vicente Scheide talesvicente826@hotmail.com Yuri Thomé Machado Strey machadoyt@gmail.com Túlio Meyer Graziottin tgraziottin@gmail.com 1 Research Laboratory of Pathology, Health Sciences Federal University of Porto Alegre (UFCSPA), 245 Sarmento Leite, Porto Alegre, RS 90050-170, Brazil 2 Departament of Urology, Santa Rita Hospital, Hospital system of the Porto Alegre Holy House of Mercy, Porto Alegre, Brazil Pathology & Oncology Research https://doi.org/10.1007/s12253-018-0389-5