Nucleocytoplasmic ß-catenin expression contributes to neuroendocrine differentiation in muscle invasive bladder cancer.

Bladder cancers are heterogeneous in nature, showing diverse molecular profiles and histopathological characteristics, which pose challenges for diagnosis and treatment. However, understanding the molecular basis of such heterogeneity has remained elusive. This study aimed to elucidate the molecular landscape of neuroendocrine-like bladder tumors, focusing on the involvement of ß-catenin localization. Analyzing the transcriptome data and benefiting from the molecular classification tool, we undertook an in-depth analysis of muscle-invasive bladder cancers to uncover the molecular characteristics of the neuroendocrine-like differentiation. The study explored the contribution of transcription factors and chromatin remodeling complexes to neuroendocrine differentiation in bladder cancer. The study revealed a significant correlation between ß-catenin localization and neuroendocrine differentiation in muscle-invasive bladder tumors, highlighting the molecular complexity of neuroendocrine-like tumors. Enrichment of YY1 transcription factor, E2F family members, and Polycomb repressive complex components in ß-catenin-positive tumors suggest their potential contribution to neuroendocrine phenotypes. Our findings contribute valuable insights into the molecular complexity of neuroendocrine-like bladder tumors. By identifying potential therapeutic targets and refining diagnostic strategies, this study advances our understanding of endocrinology in the context of bladder cancer. Further investigations into the functional implications of these molecular relationships are warranted to enhance our knowledge and guide future therapeutic interventions.

Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the presence of predisposing systemic diseases for chronic kidney disease.

Aim of this study is to compare the effects of partial nephrectomy (PN) and radical nephrectomy (RN) for stage I renal cell carcinoma (RCC) on renal functions in patients with diabetes mellitus (DM) and/or hypertension (HT). Charts of patients who underwent surgery for stage I RCC in our department were retrospectively reviewed and patients with DM and/or HT were enrolled. Preoperative and postoperative estimated glomerular filtration rates (eGFR) were calculated according to the Modification of Diet in Renal Disease (MDRD) formulation for both RN and PN groups. Groups were compared for patient demographics, preoperative eGFR, postoperative eGFR and ΔeGFR [(preoperative eGFR) - (postoperative eGFR)] which reflects the renal functional loss. There were 85 patients in the RN and 33 patients in the PN groups. Demographic data were similar but the patients in the PN group had smaller tumor size compared to RN group (32.2 ± 11.8 mm vs 47.1 ± 15.2 mm, p < 0.001). Preoperative eGFR did not differ between groups (75 ± 28.4 mL/min/1.73 m2 vs 75.5 ± 23.8 mL/min/1.73 m2 in RN and PN groups, p = 0.929). However, there were significant differences between groups in terms of postoperative eGFR (57.5 ± 21.7 mL/min/1.73 m2 vs 74 ± 27.5 mL/min/1.73 m2 in RN and PN groups, p < 0.001) and ΔeGFR (17.5 ± 4.2 mL/min/1.73 m2 vs 1.5 ± 0.4 mL/min/1.73 m2 in RN and PN groups, p < 0.001). Our findings favor the use of PN over RN for stage I RCC whenever feasible in patients with predisposing systemic diseases for chronic kidney disease for better preservation of renal functions.

Clinical Behavior of Bladder Urothelial Carcinoma in Young Patients: A Single Center Experience.

Background. There is not enough evidence about clinical behavior of bladder cancer in younger patients. Objective. We aimed to evaluate the clinical characteristics and prognosis of bladder urothelial carcinoma patients under the age of 40 years. Methods. Medical records of patients listed in our cancer database were retrospectively reviewed. A total of 40 patients who were initially diagnosed with bladder urothelial carcinoma at the age less than 40 years were included in the study. Patients' records were reviewed for recurrence and progression rates, demographic data, medical history, and treatment modalities. Results. Pathological results revealed 33 (82.5%) Ta low-grade, 6 (15%) T1 high-grade, and 1 (2.5%) T2 high-grade urothelial carcinomas. Recurrence was detected in 14/39 (35.9%) patients but progression was not observed in any patients. The mean age of recurrent patients was significantly higher than nonrecurrent patients (34.8 versus 28.5 years; p < 0.05). Besides, recurrence was detected in only 1 patient with the age under 30 years (6.2%) and 13 patients (54.1%) between 30 and 40 years old, respectively (p < 0.05). Conclusion. Bladder urothelial carcinoma diagnosed at young age tends to be a low pathologic stage, with relatively low rate of recurrence and progression.

Suture granuloma after orchiectomy: sonography, doppler and elastography features.

Suture granuloma is a mass forming benign lesion that develops at the site of surgery as a foreign body reaction to non-absorbable suture material. We present a case of suture granuloma that developed at the inguinal region after orchiectomy, and define the sonography, color Doppler sonography and real-time ultrasound elastography findings in correlation with the histopathological findings.

Suture granuloma after orchiectomy: sonography, doppler and elastography features

ABSTRACTSuture granuloma is a mass forming benign lesion that develops at the site of surgery as a foreign body reaction to non-absorbable suture material. We present a case of suture granuloma that developed at the inguinal region after orchiectomy, and define the sonography, color Doppler sonography and real-time ultrasound elastography findings in correlation with the histopathological findings.

Prognostic significance of Nestin expression in pT1 high- grade bladder urothelial carcinoma patients treated with intravesical BCG.

BACKGROUND: Possible roles of nestin expression in terms of predicting intravesical BCG therapy response in T1 high grade bladder cancer patients were investigated. MATERIALS AND METHODS: T1 high grade bladder cancer patients who were treated with intravesical BCG between 1990-2009 were included. Immunohistochemical staining for nestin expression was performed. Nestin(+) and nestin(-) patients were compared in terms of recurrence and progression rates. RESULTS: Sixty-three patients were included and median follow-up time was twenty-five months. After staining; 33 patients (52.4%) were classified as nestin (+) and 30 (47.6%) as (-). Nestin (+) patients were more likely to recur compared to nestin (-) patients (60.6% vs. 30%, p<0.05). Progression rates were also higher in nestin (+) patients, although this result did not reach statistical significance (15.2 % vs. 10 %, p=0.710). CONCLUSIONS: Nestin expression, which seems effective in predicting recurrence, appears to have a potential role in the urothelial carcinoma tumorigenesis. Patients with high grade bladder cancer and positive nestin expression need close follow-up and might be informed about more tendency to recur. Further comprehensive studies including larger patient cohorts may clarify the role of nestin in bladder cancer.

The effect of tumor volume on survival in patients with renal cell carcinoma.

PURPOSE: The aim of this study was to investigate the effect of tumor volume on prognosis and the relation of tumor volume with other prognostic factors in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: The study included 46 retrospectively assessed patients with RCC (32 males and 14 females; mean age, 58.13±10.47 years) who underwent surgery between January 2002 and January 2009. Patients were staged according to clinical, radiological, and pathological data. The basic radiological characteristics of tumors and tumor volumes were defined by two observers. The clinical information and the last health status of all patients were recorded. The life duration of the patients after surgery was determined, and cumulative survival rates were calculated. RESULTS: The survival rates showed no difference between the male and female patients (P = 0.569); the five-year survival was 75.7% and 78.5%, respectively. The survival rates demonstrated differences between groups according to potential prognostic markers such as cell type, Fuhrman's grade, the diameter, invasion of perinephric fat, sinus, or adrenal gland, pathological stage, and presence of metastasis. The inter- and intra-observer reliability of radiological volume measurements were 93.6% and 100%, respectively (P < 0.001). Two groups of tumor volume (i.e., smaller and greater than 110 cm < sup > 3 < /sup > ) showed statistically significant difference in terms of survival (P < 0.032). In univariate analysis, only Fuhrman's grade and T stage were independent prognostic variables. CONCLUSION: Tumor volume is predictive of survival in patients with RCC; however, it does not appear to be an independent prognostic factor. The prognostic factors for overall survival are Fuhrman's grade and T stage.

Histologic grading of urothelial papillary neoplasms: impact of combined grading (two-numbered grading system) on reproducibility.

The clinical management of tumor patients is often strongly influenced by the tumor grade. The presence of heterogeneity is well recognized in a variety of tumors. Overall grade is based on highest grade area identified within a tumor. Urothelial carcinoma often contains different histological grades within the same tumor. This study investigates the impact of a combined grading system on the reproducibility of papillary urothelial neoplasms. A set prepared for an earlier study consisting of ten cases of each category (papillary urothelial neoplasm of low malignant potential (PUNLMP), LGPUC, and HGPUC) was used. Agreement between pairs of pathologists was evaluated using κ statistics for the combined scoring system. Interobserver agreement was fair to substantial as reflected by κ values ranging from 0.24 to 0.74 (mean κ = 0.43). The combined scores of 2 and 3 which included PUNLMP showed the lowest degree of agreement and when this category was excluded from the analysis, interobserver agreement increased significantly (mean κ = 0.65; ranging from 0.43 to 0.92) in terms of combined scores of 4, 5, and 6. PUNLMP has been shown to be the least reproducible component of a combined scoring system even among experienced observers. Exclusion of PUNLMP from grading scheme seems to improve interobserver variability.

Significance of P-glycoprotein, p53, and survivin expression in renal cell carcinoma.

OBJECTIVES: This study addresses the relationship between cell cycle control protein p53, apoptosis inhibitor gene survivin, and chemotherapy resistance protein P-glycoprotein (P-gp) expression, and their prognostic impact in renal cell carcinoma (RCC). METHODS: A group consisting of 104 patients with RCC was included from a predefined period of time. The median follow-up was 46 months. Tumor stage was defined according to the 2002 Tumor-Node-Metastasis staging system, and Fuhrman nuclear grading was used. Expression of p53, survivin, and P-gp was assessed on immunohistochemically stained slides of the representative blocks of the tumors. RESULTS: A significant relationship was found between survival and histologic subtype (P = 0.001), tumor stage (P = 0.011), and tumor grade (P < 0.001). Although there was inverse correlation between p53 expression and stage (P = 0.014) and grade (P = 0.04), no correlation was observed with the histopathologic type or survival. There was no correlation between survivin expression and histologic subtype, stage, or survival, but there was a significant inverse correlation between survivin expression and tumor grade (P = 0.018). No significant correlation was found between any parameters tested, and P-gp expression. CONCLUSIONS: Survivin, P-gp, and p53 expression do not play a role in prognosis of RCC. Our results suggest that survivin expression may be positively regulated by mutant p53 in RCC, and this expression may have an impact on resistance to chemotherapy in RCC.

Ezrin immunoreactivity in renal cell carcinomas.

OBJECTIVE: To determine ezrin's association with clinicopathologic features and to investigate the possible effects of the presence of ezrin on the differential diagnosis of subtypes of renal cell carcinoma (RCC). STUDY DESIGN: Ezrin reactivity was examined immunohistochemically in tumor tissues obtained from 78 patients who underwent radical nephrectomy for renal cell carcinoma. Correlation between ezrin expression and RCC subtypes was investigated and compared with tumor stage, grade and other clinicopathologic parameters. RESULTS: There was no correlation between ezrin expression and clinicopathologic features. Furthermore, a significant correlation was found between ezrin reactivity and subtypes of RCC (p = 0.002). Ezrin reactivity was observed mainly in conventional, papillary and mucinous tubular spindle cell carcinoma (MTSCC) subtypes of RCC, while none of the chromophobe RCC was positive for ezrin. Sarcomatoid and unclassified subtypes of RCC were found to be faint and/or negative for ezrin reactivity. CONCLUSION: Investigation of ezrin reactivity may be beneficial as an additional diagnostic marker in the differential diagnosis of RCC subtypes. Also, it seems to be useful to designate the origin of MTSCC.

Expression of cathepsin D in bladder carcinoma: correlation with pathological features and serum cystatin C levels.

AIMS AND BACKGROUND: The aim of this study is to evaluate the expression of cathepsin D in primary bladder cancer and to determine its relationship with conventional pathological features and serum cystatin C levels. METHODS: The immunohistochemical cathepsin D expression and staining patterns of epithelial and stromal cells were investigated in 21 patients with primary bladder carcinoma. Serum cystatin C levels were determined by immunoturbidimetry and compared with matched controls. RESULTS: There were 7 papillary neoplasms of low malignant potential, 7 low-grade and 7 high-grade carcinomas. Six tumors were invasive. Statistical analysis showed a significant inverse relationship between cathepsin D expression of the tumor cells and tumor grade and stage (P = 0.018 and P = 0.046, respectively). Serum cystatin C levels of the controls and patients varied between 0.39 mg/L and 1.99 mg/L (P > 0.05). There was no significant relation between cathepsin D expression in tumor tissue and serum cystatin C levels. CONCLUSIONS: Loss of cathepsin D expression in bladder carcinomas may be associated with high-grade and invasive tumors. Thus, increased cathepsin D expression by tumor cells may be related to local tumor invasion at an early stage, but it seems that extracellular cystatin C is not affected by cathepsin D expression of tumor or stromal cells, and cystatin C concentrations are not directly correlated with the progression of primary bladder carcinomas.

Vascular endothelial growth factor expression in untreated and androgen-deprived patients with prostate cancer.

The aim of the study was to investigate immunohistochemically the expression of vascular endothelial growth factor (VEGF) in untreated and androgen-deprived patients with prostate cancer. The study included 20 patients with prostate cancer who had undergone transurethral prostatectomy due to infravesical obstruction. All patients had been receiving androgen deprivation therapy for at least 3 months. Transurethral prostatectomy specimens were examined for VEGF expression after androgen deprivation, and the biopsy samples of the same patients were used for the evaluation of VEGF expression before androgen deprivation. VEGF expression was analyzed using immunohistochemistry. Staining patterns determined by the staining scores were compared before and after treatment. The correlation of VEGF expression with PSA, Gleason score, and the percent change in PSA after treatment was also investigated. Eligible biopsy specimens were available in 15 of the 20 patients, allowing for the evaluation of VEGF expression before treatment. All prostate cancer specimens were positive. VEGF was localized mainly in the cytoplasm or on the membrane of carcinoma cells. Staining was strong in 86.7% of patients before androgen deprivation. Heterogeneous staining (strong in 25%, moderate in 35%, and weak in 40%) was observed after treatment. Staining scores were significantly higher in patients before androgen deprivation and showed a significant decrease after androgen deprivation (p = 0.007). Tumor staining correlated with Gleason score. No significant correlation was determined between VEGF expression and pre-treatment PSA and percent change of PSA after treatment. Immunohistochemical results indicate that VEGF expression is downregulated by androgen deprivation therapy. VEGF may be a potential target for therapeutic intervention in prostate cancer.

Echo contrast-enhanced power Doppler ultrasonography for assessment of angiogenesis in renal cell carcinoma.

OBJECTIVE: Tumoral growth is an angiogenesis-dependent event. Although there are studies about the importance of histopathologic angiogenesis in various malignancies, the assessment of the angiogenesis by radiologic techniques is not well established. The aim of this study was to investigate the efficacy of echo contrast-enhanced power Doppler ultrasonography (PDUS) in determining the angiogenic status of renal cell carcinoma (RCC). METHODS: Power Doppler ultrasonography was performed before and after intravenous administration of an echo contrast agent in 42 patients with renal masses. Twenty-one of these renal masses were diagnosed as RCC histopathologically, and these 21 patients were reevaluated retrospectively. The color pixel ratios of selected images were calculated as the ratio of the number of pixels showing power Doppler signals to the total number of pixels within the lesion. The results were compared with the histopathologic microvessel density (MVD). RESULTS: A significant correlation was found between color pixel ratio and MVD values in both PDUS techniques. The use of the echo contrast agent improved this correlation and P values (Spearman rho from 0.436 to 0.551; P from .048 to .01). CONCLUSIONS: Color pixel ratio values reflect the MVD in RCC. Therefore, these results suggest that preoperative quantification of angiogenesis can be possible with the help of PDUS in RCC.

Significance of COX-2 expression in human renal cell carcinoma.

OBJECTIVES: To evaluate the expression of cyclooxygenase-2 (COX-2) and its association with clinicopathologic parameters, and to investigate the relationships between COX-2 expression and inflammation and carcinogenesis in human renal cell carcinoma. COX-2 expression is associated with aggressive clinicopathologic parameters and an unfavorable prognosis in several human malignancies. METHODS: COX-2 expression was examined immunohistochemically in tumor tissues obtained from 71 patients who underwent radical nephrectomy for renal cell carcinoma. The correlation between COX-2 expression and clinicopathologic findings and patient survival was determined. RESULTS: Of 71 tumors, 63.4% were positive for COX-2 expression. Correlation was found between COX-2 expression and various clinicopathologic features, including tumor size, tumor stage, and tumor grade (P = 0.038, P = 0.004, and P = 0.004, respectively). We found no relationship between COX-2 expression and patient survival. However, the immunoreactivity of COX-2 in renal cell carcinoma and peritumoral areas with inflammation was greater than in areas without inflammation. A statistically significant correlation was found between COX-2 expression and the tubules associated with inflammation (P = 0.038). CONCLUSIONS: COX-2 expression in patients with renal cell carcinoma is associated with several clinicopathologic features. COX-2 expression seems to play a role in the inflammation-carcinoma sequence in renal cell carcinoma. Additional research is required to determine the link between carcinogenesis and inflammation in renal cell carcinoma.

Urothelial carcinoma of the bladder with trophoblastic differentiation: a case report.

We report a case of a urothelial carcinoma with trophoblastic differentiation of the bladder that occured in a 23-year-old man. The patient presented with hematuria. Multiple papillary masses were resected transurethrally. Histopathologically, grade III urothelial cell carcinoma contained giant cells that were positive for human chorionic gonadotrophin (HCG), placental alkalen phosphatase, and human placental lactogen. HCG secreting tumors are reported to be highly aggressive. The patient is alive and well without evidence of recurrent disease or metastasis at 10 months from transurethral resection. To our knowledge, this case is the youngest patient in the literature so far.

Reproducibility of the 1998 World Health Organization/International Society of Urologic Pathology classification of papillary urothelial neoplasms of the urinary bladder.

OBJECTIVES: This study assessed the diagnostic agreement and intra- and inter-observer reproducibility of the World Health Organization/International Society of Urologic Pathology Consensus Classification of Urothelial Neoplasms (1998 WHO/ISUP classification) and the 1973 WHO classification. METHODS: A teaching set with 5 slides of each papillary neoplasm of low malignant potential, low-grade papillary carcinoma, high-grade papillary carcinoma, and a guideline, as well as a study set of 30 slides containing ten cases of each category, were sent to participants. Six pathologists expert in urological pathology reviewed the 30 slides of non-invasive papillary urothelial tumors in the study set. Diagnostic accuracy and reproducibility were evaluated using intra- and inter-rater techniques (kappa statistic). RESULTS: A moderate to substantial intra- and inter-observer reproducibility was achieved for both the 1998 WHO/ISUP and 1973 WHO classification. The results of the two classification systems were not different statistically ( P>0.05). Reproducibility was lower in low-grade tumors for both classifications. CONCLUSIONS: The new proposed classification system for non-invasive urothelial neoplasms does not increase the reproducibility. There is still a need for uniformity in grading in order to compare the different studies and therapies and to provide more accurate information for management.

Expression of p53 and mdm2 and their significance in recurrence of superficial bladder cancer.

The purpose of this study is to evaluate the expression of p53 and mdm2 and to determine whether they may be used as additional predictors of recurrence in superficial transitional cell carcinoma of the bladder. Paraffin sections of 80 patients with superficial transitional cell carcinoma of the bladder, who were treated with transurethral resection, were stained with p53 and mdm2 antibodies using the standard avidin biotin immunoperoxidase method. Nuclear staining for both p53 and mdm2 was calculated as the percentage of labeled nuclei out of a total number of tumor cells counted. The percentage of p53- and mdm2-positive cells showed a significant relationship with tumor grade and recurrence (p = 0.002 and p = 0.016; p = 0.01 and p = 0.003, respectively). In addition, a weak inverse relationship was found between p53 and mdm2 values (r = -0.184). p53 and mdm2 reactivities are valuable parameters in predicting recurrence in superficial bladder cancer. Thus, mdm2 expression appears to play a role in predicting biologic behavior in superficial transitional carcinoma of the bladder.