Urologic Oncology: Seminars and Original Investigations
Original articleExpression of cell cycle-associated proteins in non-muscle-invasive bladder cancer: Correlation with intravesical recurrence following transurethral resection
Introduction
Approximately 80% of newly diagnosed bladder cancers are non-muscle-invasive tumors that are limited to the urothelium or infiltrate no deeper than the lamina propria. Complete transurethral resection (TUR) of the visible tumor burden is the current standard of care in patients with non-muscle-invasive bladder cancer (NMIBC), and the prognosis of such patients is generally favorable, achieving survival rates at 5 years greater than 80% [1]. However, intravesical recurrence following TUR has been reported in 30% to 80% of patients with NMIBC [1], [2], [3]. Intensive efforts, therefore, have been made for the development of systems precisely predicting the outcome of TUR, which are of great utility in planning both postoperative adjuvant therapy and follow-up schedule in an individual patient.
Although a number of investigators have identified risk factors associated with intravesical recurrence of NMIBC, including tumor multiplicity, maximal tumor size, grade, stage, growth pattern, and microvascular invasion [3], [4], [5], [6], [7], the outcomes of these studies are not consistent. Hence, in order to provide more reliable information regarding the probability of intravesical recurrence in patients with NMIBC following TUR, several studies have investigated the value of a wide variety of molecular markers, and some of these molecules were shown to be significantly related to postoperative prognostic outcomes [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]. For example, Choi et al. performed cDNA microarray analysis and identified metalloproteinase-1 and -12, transforming growth factor-β1, vascular endothelial growth factor, and fos as useful predictors of recurrence in patients with low grade NMIBC [13]. We also previously reported the significantly higher intravesical recurrence rate in patients with strong clusterin expression in resected NMIBC specimens than in those with weak expression [14]. However, to date, there are no established systems for predicting clinical outcomes in patients with NMIBC who were treated with TUR; therefore, it would be an attractive approach to incorporate the profile of molecular markers into currently available clinicopathologic information of NMIBC to accurately predict the postoperative recurrence of NMIBC.
Considering these findings, we focused on the significance of markers involved in cell cycle regulation, which has been shown to be a key event in determining the biological behavior of NMIBC [19], evaluated the expression level of 7 potential cell cycle-associated proteins, including Aurora-A, c-erbB2, cyclin-D1, Ki-67, p21, p27, and p53, in TUR specimens with immunohistochemical staining, and analyzed these outcomes according to several clinicopathologic parameters.
Section snippets
Patients and methods
This study included a total of 161 consecutive patients who were treated with TUR of newly diagnosed primary urothelial carcinoma of the bladder between January 2000 and December 2007, and were subsequently diagnosed as having NMIBC (i.e., stage Ta or T1 tumor). Tumor size is defined as the largest tumor measured with a resection loop that is 1 cm long. The growth pattern was macroscopically classified into either papillary or non-papillary type. Complete resection of all visible tumors was
Results
During the observation period of this study (median, 47 months; range, 13–93 months), 71 of the 161 patients (44.1%) developed disease recurrence, and 1-, 3-, and 5-year recurrence-free survival rates were 67.7%, 53.9%, and 45.2%, respectively (Fig. 1). In addition, progression to muscle-invasive disease was detected in 5 of the 161 patients (3.1%), who subsequently underwent radical cystectomy. Table 1 summarizes the characteristics of 161 patients included in this study according to whether
Discussion
Despite a number of studies that evaluated the factors predicting intravesical recurrence following TUR of NMIBC, these studies are sometimes difficult to compare, resulting in a failure to show consistent findings [3], [4], [5], [6], [7]. This could be due to several factors as follows: (1) indications of intravesical therapy after TUR differed at each institution; (2) the same variable has been evaluated according to different cut off points; (3) the study designs varied from small
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Immunohistochemical expression of Ki-67, Cyclin D1, p16INK4a, and Survivin as a predictive tool for recurrence and progression-free survival in papillary urothelial bladder cancer pTa / pT1 G2 (WHO 1973)
2019, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :Statistical tools for the MD like RSF and LASSO, have shown that they can be used in the selection of variables, such as IHC markers, pondering their participation in the behavior of this specific type of bladder tumor. With respect to the IHC markers selected, there was a prognostic utility of Cyclin D1 nuclear expression and p16INK4a citoplasmatic expression in terms of recurrence-free survival [19,20]. Our results confirm this association specifically in the UBC pTa/pT1 G2 (WHO 1973).
Expression profile of epithelial-mesenchymal transition markers in non-muscle-invasive urothelial carcinoma of the bladder: Correlation with intravesical recurrence following transurethral resection
2015, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :In this series, the indication for adjuvant intravesical instillation therapy was generally determined according to the pathological findings showing the presence of concomitant carcinoma in situ (CIS) or T1G3 disease or both; therefore, bacillus Calmette-Guérin was administered for most patients who received adjuvant intravesical instillation therapy. Follow-up after TUR of NMIUCB was performed based on the schedule, as previously described [10]: cystoscopy and urinary cytological examination were performed every 3 to 6 months for 3 years after TUR, and then every 6 to 12 months until 5 years after TUR, and intravenous pyelography was performed every 6 to 12 months for 5 years after TUR. When detecting tumors or hyperemic mucosa by cystoscopy or positive findings on urinary cytology, TUR of the tumor or transurethral biopsy of the abnormal region or a combination of both was performed.
Urinary immunocytology-Promise or nonseller? A review with an opinion
2014, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :With regard to oncoproteins and tumor suppressors probably a combination of candidates yields additional diagnostic information, such as a combination of cell cycle–regulating proteins p53, pRb, p21, and p27 [78]. Expression of p21 can—unlike other cell cycle–associated proteins—together with clinical parameters, tumor size, and accompanying carcinoma in situ helps predict the tendency for recurrence of non–muscle-invasive bladder carcinomas [79]. Immunocytochemistry of p16 (INK4a) can improve the detection of low-grade [80] and high-grade [81] urothelial carcinomas.
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