Normal human macula densa morphology and cell turnover: A histological, ultrastructural, and immunohistochemical investigation.

The aim was to analyze the morphology of normal human macula densa (MD), evaluate the cells that may be responsible for its turnover, and collect quantitative data. Of four samples of normal human renal tissue, two were embedded in resin to measure the longitudinal extension and examine the ultrastructure of the MD, the other two were embedded in paraffin to study apoptosis and cell proliferation. The MD is composed of a monolayer tissue about 40 µm long, which includes 35-40 cells arranged in overlapping rows. Ultrastructurally, MD cells show two polarized portions: an apical end, with sensory features, and a basolateral aspect, with paracrine function. MD cells are connected apically by tight junctions, with/without adherens junctions, which form a barrier between the distal tubule lumen and the interstitium. Cells in degeneration, often associated with macrophages, and undifferentiated cells were found in the MD and adjacent distal tubule. A filamentous mat previously described in proximal tubule scattered tubular cells (STCs) was detected in the basal cytoplasm in undifferentiated cells. The tissue was consistently negative for the proliferation marker Ki67 and for the apoptotic markers caspase-3 and caspase-9. This work confirms our earlier morphological findings and provides new data: (a) MD cells display both apical adherens and tight junctions, the latter forming a tubulo-mesangial barrier; (b) the MD is a monolayer made up of about 40 cells arranged in rows; (c) the simultaneous presence of degenerating (8-13%) and undifferentiated (4-13%) cells reminiscent of STCs suggests a non-negligible cell turnover.

Prognostic role of BAP1 in pT1 clear cell carcinoma in partial nephrectomy specimens.

BAP1 is a gene situated on chromosome 3p in a region that can be modified in renal cell carcinomas (RCCs). Mutations that cause loss of expression of BAP1 frequently occur in primary clear cell renal carcinoma (ccRCC). In a previous work, we observed that loss of nuclear BAP1 expression was crucial in ccRCC progression; in the current study, we investigated BAP1 expression in a large series of small conventional ccRCCs treated with partial nephrectomy, to assess a possible role as biomarker and the prognostic value in terms of patients' survival at long-term follow-up. One hundred sixty-two patients with single pT1 ccRCC were selected from those who underwent surgery at our Institute of Urology between 1987 and 2000. The features considered in this study were gender, age, tumor size, grade, incidence of metastasis, and patient-specific survival; they were correlated with immunohistochemical BAP1 nuclear expression in tumoral tissue. Median follow-up was 197.24 months (range 19 to 274); median survival was 125.34 months (range 5 to 274 months). None of our pT1 ccRCCs showed total loss of nuclear BAP1 staining; we found a significant negative correlation between nuclear BAP1 expression and tumor size and between nuclear BAP1 expression and grade. In small ccRCCs, nuclear BAP1 staining was not correlated with disease-specific 5-year survival.Our data confirm the established role of BAP1 as a tumor suppressor protein. This is the first report where BAP1 has been studied in pT1 ccRCC tumors, but nuclear BAP1 expression cannot help identify patients having high-risk disease in these patients.

Non-muscle invasive high grade urothelial carcinoma of the bladder. Which factors can influence understaging at the time of radical cystectomy?

OBJECTIVE: To evaluate the main factors which influence understaging in patients with T1G3 non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: 109 patients with T1/G3 underwent transurethral resection of bladder tumor (TURBT) and then radical cystectomy (RC) with pelvic lymph nodes dissection. A number of variables were considered when evaluating the detection of understaging. We considered the patients age and gender, as well as the size, number, location and morphology of their tumor. We also considered coexistence of bladder carcinoma in situ (CIS), microscopic vascular invasion and deep lamina propria invasion. The level of experience of the surgeon was also analyzed. RESULTS: in RC samples muscle invasion, that is understaging, was detected in 74 (67.9%) patients, while 35 (32.1%) patients were appropriately staged. In these cohort of patients with high grade tumors, understaging was associated with deep lamina propria and microscopic vascular invasion, multiple tumors, tumor size > 6 cm, tumor location (trigone and dome), presence of residual tumor; age, gender, tumor morphology, CIS associated, and experience of urological surgeon were not associated with clinical understaging. CONCLUSIONS: in our study, evaluating patients with high grade NMIBC at first TURBT, we identified some risk factors that need to be considered and that are able to increase the risk of understaging: deep lamina propria and microscopic vascular invasion, multiple tumors, tumor size > 6 cm, tumor location (trigone and dome), presence of residual tumor. When these risk factors are present, performing an early cystectomy, and not a re-TURBT, could lower the risk of worse pathological finding due to rapid disease progression of the high grade tumors, and can prolong survival.

Spontaneous recurrent hematuria and hematospermia: Unique manifestations of von Willebrand disease type I. Case report.

In this report we describe the case of a patient with unrecognized von Willebrand disease (vWD), in whom the only presenting symptoms were spontaneous and recurrent hematuria with bladder tamponade, associated with recurrent hematospermia. The diagnosis was made only after several admissions to the hospital. We suggest to include coagulopathies such as vWD as part of the evaluation in patients with unexplained genito-urinary bleeding.

Loss of nuclear BAP1 protein expression is a marker of poor prognosis in patients with clear cell renal cell carcinoma.

INTRODUCTION: BRCA1-associated protein 1 (BAP1) is a gene situated on chromosome 3p in a region that is deleted in more than 90% of renal cell carcinomas (RCCs). In the present study, we studied BAP1 immunohistochemical expression in a large series of conventional clear cell RCCs (ccRCCs) treated with radical nephrectomy; we assessed the prognostic value of their expression in terms of patients׳ survival at long-term follow-up. MATERIALS AND METHODS: A total of 154 consecutive patients with ccRCC were selected from a prospective database and considered for the study purpose; all patients were treated with radical nephrectomy and lymphadenectomy at our Institute of Urology between 1983 and 1985. The features considered in this study were tumor size, grade and stage, vascular and capsular invasion, incidence of metastasis, and patient-specific survival; all these parameters were correlated with immunohistochemical cytoplasmic and nuclear expression of BAP1 in tumoral tissue. RESULTS: Median follow-up was 196.18 months and median survival was 125.34 months. Nuclear BAP1 expression showed a high frequency of loss in tumoral cells; nuclear BAP1-negative tumors had higher tumor size, higher Fuhrman grade, and higher stage, a greater amount of vascular and capsular invasion and a higher incidence of metastases. In multivariate analysis, pathological stage and nuclear BAP1 expression resulted independent prognostic factors. CONCLUSION: We have demonstrated that nuclear BAP1 expression is a marker of prognosis in ccRCC, having an influence on cancer-specific survival. The clinical importance for BAP1 will be realized with the identification and application of targeted therapies and with individualized approaches in the adjuvant setting or in the metastatic setting or in both the settings.

Enhanced Efficacy of Combinations of Pexiganan with Colistin Versus Acinetobacter Baumannii in Experimental Sepsis.

We investigated the efficacy of colistin combined with pexiganan in experimental mouse models of Acinetobacter baumannii infection.Adult male BALB/c mice received intraperitoneally 1 mL saline containing 2 × 10 CFU of susceptible and multiresistant A. baumannii. Two hours after bacterial challenge, animals received 1 mg/kg of colistin, 1 mg/kg of pexiganan, or 1 mg/kg of colistin plus 1 mg/kg of pexiganan.Blood culture positivity, the quantities of bacteria in the intra-abdominal fluid, the rate of lethality and immunological studies, such as immunophenotyping and NK cytotoxicity, were evaluated.In the in vitro study, A. baumannii showed susceptibility to colistin and pexiganan and a strong synergy was observed by testing colistin combined with pexiganan with fractionary inhibitory concentration index of 0.312 for both strains.In the in vivo study colistin or pexiganan alone showed a good antimicrobial efficacy. When colistin was combined with pexiganan, the positive interaction produced low bacterial counts that were statistically significant versus singly treated groups. For both strains the highest rate of survival was observed in combined-treated groups (90%).Pexiganan increased NK cytotoxic activity over the levels of infected and colistin-treated animals.In conclusion, pexiganan combined with colistin was found to be efficacious against A. baumannii infection.

Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer.

PURPOSE: Evidences have shown that neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with cancer. We wanted to test the prognostic significance of NLR in prostatic cancer of patients who are candidate to radical prostatectomy. METHODS: We have considered 731 patients. Complete demographic data including age, tumor stage, Gleason score, complete blood count and serum biochemical profile were collected. Pre-treatment percentage of neutrophils and NLR were considered, and correlated with patients data and recurrence free survival. RESULTS: 389 patients were evaluated, mean age 65 years, mean follow-up 51.5 months, mean recurrence free survival 51.3 months. Total neutrophil count does not correlate with biochemical recurrence and disease free survival. Patients with a value higher of 60% of neutrophils are more likely to have a recurrence. Patients with a total lymphocyte count <1,500 have a higher rate of relapse. NLR was not correlated with baseline total PSA, with Gleason score and with pathological stage; patients with a NLR >3 has a higher incidence of recurrence. In multivariate analysis including age, total PSA and NLR, NLR is the most important factor able to predict recurrence. There are some limitations to this study; first, this is a retrospective study, and the total number of patients analyzed is relatively small. CONCLUSIONS: Our study suggests that pre-treatment NLR may be associated with disease free survival in patients with prostate cancer, and could be introduced in clinical practice. NLR has the advantage of low economic cost and wide availability.

A conservative approach to perineal Fournier's gangrene.

Fournier's gangrene (FG) is a disease involving necrosis of perineum and external genitalia; in 95% of cases it is possible to diagnose the Fournier's gangrene just by physical examination. The clinical presentation of FG varies from an initial localized infection to large areas with necrotizing infection. The disease typically affect elderly men (6°-7° decade) with important systemic comorbidities; women are less frequently affected. Despite improvements in diagnosis and management, the mortality rate nowadays is between 20% and 43%. The severity and mortality of the disease is dependent upon the general condition of the patient at presentation and upon the rate of spread of the infection. Treatment involves a multidisciplinary approach: intensive systematic management, broad-spectrum antibiotic therapy, early surgical debridement (wide abscission of necrotic tissues and surgical drainage of peritoneum, scrotum, penis, and inguinal areas), hyperbaric oxygen therapy; surgery can eventually be repeated if necessary; reconstructive surgery has an important role in the final treatment of the disease. The technical difficulties frequently encountered and the inability to make a complete removal of the necrotizing tissues at the time of surgery in some cases has led to the application of combined techniques, in view of the enhancement effect of specific advanced medications, targeted antibiotic therapy and hyperbaric medicine. We have considered 6 patients affected by Fournier's gangrene treated at our institution; all the patients received treatment with the help of plastic surgeons of the same institution. After debridement, all the patients were treated with advanced specific dressings consisting of plates and strips made of calcium alginate, hydrogels and polyurethane and twodimensional cavity foams. Reconstructive surgery was necessary in one case. Hyperbaric oxygen therapy (HBO) has been performed in all cases. The multidisciplinary approach, the combined use of HBO therapy and the adoption of advanced specific dressings, have made possible the complete healing of the lesions in a shorter period, avoiding further surgery in 5 out of 6 patients.

Is it possible to predict the need of inguinal lymphadenectomy in patients with squamous cell carcinoma of the penis? A clinical and a pathological study.

OBJECTIVE: to investigate the role of CD- 44 immunohistochemical expression within tumoural and non-tumoural tissue, aiming to understand if it can help us to predict the need of performing inguinal lymph nodes dissection to complete surgery of the penis. MATERIALS AND METHODS: CD44 immunohistochemical expression was investigated in tissue specimens from 39 patients with squamous cell carcinoma of the penis who underwent partial or total penectomy between 1987 and 2008. Patient age, tumour size, and grade; CD44 intensity score, cytological expression, topographic and distribution pattern were evaluated by immunohistochemistry on archived material and correlated with disease-specific survival. RESULTS: mean patients age was 67.7 years; mean followup was 130.44 months. Bilateral inguinal lymphadenectomy was performed in 14 patients; there were 8 N+ patients (23.5%). pTis-pT1 vs. > pT1 and the EAU classification of risk group resulted to be predictive of lymph nodal metastases at univariate analysis (respectively p = 0.006 and p = 0.045), but not the grading. The intensity score, cytological expression, topographic and distribution pattern of CD44 staining did not correlate with stage, grade and lymph nodes metastases. All disease related deaths occurred only in patients showing an high CD44 intratumoral expression, but this correlation is not statistically significant. Multivariate analysis showed that only lymph node metastasis was an independent prognostic factor predictive of lymph nodes metastases. CONCLUSIONS: CD44 expression in patients with squamous cell carcinoma of the penis is not able to predict the need of performing inguinal lymphadenectomy; staging and the EAU classification of risk group resulted to be predictive of lymph nodal metastases.

Survival in patients with clear cell renal cell carcinoma is predicted by HIF-1α expression.

AIM: To investigate hypoxia inducible factor-1α's (HIF-1α) immunohistochemical expression in clear cell renal cell carcinoma (ccRCC) treated with radical nephrectomy. PATIENTS AND METHODS: One hundred and forty-eight patients were considered from those who underwent radical nephrectomy between 1983 and 1993. Archived materials were retrieved from the Institute of Pathological Anatomy for immunostaining. The features considered on the histological specimens were tumor stage, grade, as well as cellular and vascular HIF-1α expression. All considered parameters were correlated with time to recurrence (TTR) and overall survival (OS). RESULTS: TTR was significantly longer in patients with low cellular HIF-1α expression; patients' survival was higher in those with low HIF-1α expression. Regarding vascular HIF-1α expression, the differences were not statistically significant when considering TTR and OS. On univariate analysis, age, clinical stage and HIF-1α cellular expression showed a significant association with OS. CONCLUSION: Cellular HIF-1α is an important indicator of prognosis in patients with ccRCC; high HIF-1α expression predicts poor survival.

Recent aspects of sunitinib therapy in patients with metastatic clear-cell renal cell carcinoma: a systematic review of the literature.

Sunitinib is an orally available inhibitor of multiple tyrosine-kinase receptors approved for the treatment of advanced clear-cell renal cell carcinoma (ccRCC), a disease which has habitually had a very poor patient survival rate. Although it has become the most widely used drug for this disease, it remains not completely clear the best treatment strategy with these agent. The aim of this review is to highlight the most recent and interesting aspects of the research on treatment of advanced ccRCC with sunitinib and eventually determine alternative treatment schedule to reduce the incidence of side effects; we also wanted to review recent biomarkers able to predict response to therapy and also to point out the mechanism of acquired resistance to this drug.

Tumor VEGF expression correlates with tumor stage and identifies prognostically different groups in patients with clear cell renal cell carcinoma.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is a potent inducer of tumor angiogenesis and represents the key element in the pathogenesis of clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the use of tumor VEGF expression as a parameter to identify tumor stage and prognostically different patient groups. METHODS AND MATERIALS: We retrospectively collected clinical data of 137 patients treated with partial or radical nephrectomy at our institutions for organ-confined, locally advanced, and metastatic ccRCCs between 1984 and 2013. Tumor cell VEGF immunohistochemical expression was compared with pathological and clinical features including age, sex, tumor stage, and Fuhrman grade. Comparison of VEGF expression levels between tumor stages was performed via Kruskal-Wallis nonparametric test. Survival analysis was conducted via Kaplan-Meier product-limit method, and Mantel-Haenszel log-rank test was employed to compare survival among groups. RESULTS: Median age at diagnosis was 61 years (range: 33-85 y). Tumor stage was pT1N0M0 in 67 patients (49%), pT2N0M0 in 5 (4%), and pT3N0M0 in 25 (18%), while 40 patients (29%) had metastatic tumors at diagnosis. Fuhrman nuclear grade was G1 in 22 patients (16%), G2 in 60 (44%), G3 in 33 (24%), G4 in 13 patients (9%), and unknown in 9 patients. Tumor VEGF was differentially expressed among different stages (P<0.001) and in low (G1-2) and high (G3-4) Fuhrman grade tumors (P<0.001). No significant differences were found when stratifying by sex (P = 0.06) or age (P = 0.29). Median overall survival (OS) from partial or radical nephrectomy was 161 months (range: 1-366). We observed a significantly longer OS in patients with low (<25%) vs. high (>25%) VEGF expression levels (median OS 206 vs. 65 mo, P<0.001). CONCLUSIONS: Our data show that tumor cell VEGF expression is significantly associated with tumor stage and Fuhrman grade and is able to predict patient outcome, suggesting a potential use of this parameter in identifying prognostically different patients with ccRCC.

α1-Blockers for the treatment of recurrent urinary tract infections in women with dysfunctional voiding: a prospective randomized study.

OBJECTIVES: To evaluate the therapeutic effects of tamsulosin on recurrent urinary tract infections in women with dysfunctional voiding. METHODS: A total of 155 women with recurrent urinary tract infections and dysfunctional voiding were included and randomly assigned to the following groups: uroflowmetry biofeedback (group 1), α1-adrenoceptor antagonists (group 2), uroflowmetry biofeedback combined with α1-adrenoceptor antagonists (group 3) and no treatment (group 4). Patients were evaluated by the American Urological Association Symptom Index at 3, 6 and 12 months. Urodynamics was carried out in patients of groups 1, 2, and 3 at 3, 6 and 12 months, whereas urodynamics was only carried out at 12 months in group 4. All patients were followed up for 1 year with monthly urine cultures. RESULTS: The incidence of storage and emptying symptoms decreased significantly at 3, 6 and 12 months. Mean flow rate, flow time and voiding volume increased significantly (with a better outcome in patients of group 3), whereas post-void residual urine decreased. Mean opening detrusor pressure and detrusor pressure at maximum flow decreased significantly (with a better outcome in patients of group 3). Mean urethral closure pressure and maximum urethral closure pressure decreased significantly with a more significant decrease for patients in group 3. The prevalence of urinary tract infection decreased significantly in all groups after treatment, and this decrease remained stable during the follow up. CONCLUSIONS: In women with dysfunctional voiding and recurrent urinary tract infection, tamsulosin associated with uroflowmetry biofeedback might be an effective and safe treatment option for improving urinary symptoms and quality of life.

Nebivolol induces, via ß3 adrenergic receptor, lipolysis, uncoupling protein 1, and reduction of lipid droplet size in human adipocytes.

OBJECTIVES: Most ß-blockers may induce weight gain, dysglycemia, and dyslipidemia. Nebivolol is a third-generation ß1-blocker with vasodilating properties mediated by ß3 adrenergic receptors (ß3AR). We investigated whether nebivolol is able to induce ß3AR-mediated lipolysis, uncoupling protein 1 (UCP1), and size-reduction in human adipocytes. METHODS: Human visceral (n = 28) and subcutaneous adipose tissue (n = 26) samples were used to obtain differentiated subcutaneous and visceral preadipocytes. Adipocytes were used to verify the effects of nebivolol onlipolysis, uncoupling protein 1 (UCP1) and other genes of the thermogenic program. RESULTS: Lipolysis was induced by isoproterenol and specific ß3AR agonist, as expected,and also by nebivolol at 100 nmol/l and by its L-enantiomer at 10 nmol/l (P < 0.01). Nebivolol-mediated lipolysis was blocked by SR59230A, a specific ß3AR antagonist, suggesting that nebivolol acts through ß3AR in human adipocytes. Interestingly, in human adipocytes, nebivolol activated UCP1, PPARγ coactivator-1α (PGC-1α) and cytochrome c (CYCS) gene expression in a p38 MAPK-dependent manner. Using propranolol (ß1 and ß2 antagonist) together with nebivolol we showed that the induction of these genes was still present suggesting again ß3AR activation. Moreover, nebivolol significantly reduced the diameter of lipid droplets in cultured adipocytes. CONCLUSION: In summary, nebivolol, through ß3AR, is able to induce lipolysis and promote thermogenic and mitochondrial genes. The induction of lipolysis and the thermogenic program could explain the reduction of lipid droplets size. In conclusion, the lower dysmetabolic effects of nebivolol in humans may depend on its ß3 agonist activity and the consequent induction of thermogenic program in human adipocytes.

In vitro and in vivo effects of sub-MICs of pexiganan and imipenem on Pseudomonas aeruginosa adhesion and biofilm development.

An in vitro and in vivo study was performed to quantify adhesion and biofilm formation ability of Pseudomonas aeruginosa slime producer under the effect of sub-minimal inhibitory concentrations (MICs) of pexiganan and imipenem. To evaluate adherence, squares of ureteral stents were placed in six-well tissue-culture plates containing 6 ml of a cell suspension grown in the presence of sub-MICs of study antibiotics. To evaluate biofilm formation sterilized squares were placed in six-well tissue culture plates containing 6 ml of triptic soy broth (TSB) supplemented with 0.25% of glucose and the respective amount of antibiotic. For in vivo study a biofilm infection rat model was performed. The study included an uninfected control group to evaluate the sterility of surgical procedure, a group infected with a slime-producer P. aeruginosa strain not previously treated with antibiotics and two groups infected with the strain previously treated with imipenem or pexiganan. Adherence and biofilm in vitro formation was strongly affected by pre-treatment with pexiganan and imipenem, with the latter being the more effective antibiotic. The in vivo results showed a reduction in bacterial load on the ureteral stent tissue of the pre-treated strain. Differently, urine cultures showed no differences in bacterial growth for the pre-treated strain showing that it retained its ability to cause infection. This study suggests that sub-MIC imipenem and pexiganan could be a good strategy to target the adhesion process during the infection cycle.

VEGF expression and response to sunitinib in patients with metastatic clear cell renal cell carcinoma.

AIM: To verify whether vascular endothelial growth factor (VEGF) is associated with distant metastasis free survival (DMFS) and Overall Survival (OS) of patients with renal cell carcinoma (RCC) treated with sunitinib. PATIENTS AND METHODS: We have studied 41 patients with metastatic RCC treated with radical nephrectomy, between 2008 and 2010, and sunitinib. Pathological features were compared with the Memorial Sloan-Kettering Cancer Center (MSKCC) score, DMFS, and with OS, and PFS after first-line therapy. RESULTS: Tumor stage and grade, VEGF expression and H-score correlated with MSKCC score, DMFS, and with OS; VEGF expression correlated with stage and OS. Patients with higher H-score and higher VEGF expression had a significantly shorter survival; OS after first-line sunitinib therapy and PFS correlated with MSKCC score and DMFS but not with VEGF expression and H score. CONCLUSION: Our data suggest the potential use of tumor cell VEGF expression as a prognostic marker for DMFS and OS, but VEGF does not appear promising as a marker of response to therapy.

Prognostic value of CD44 expression in penile squamous cell carcinoma: a pilot study.

BACKGROUND: Several studies have reported on the prognostic value of molecular markers for metastasis risk and survival in penile squamous cell carcinoma (SCC) patients. The usefulness of CD44 expression as such a marker has been studied in different tumors, but not in penile SCC. Our aim was to determine whether CD44 expression may serve as a prognostic marker for lymph node metastasis and survival in penile SCC patients. METHODS: CD44 immunoistochemical expression was investigated in tissue specimens from 39 patients with penile SCC. CD44 cell positivity, staining intensity and distribution were analyzed and correlated with tumor stage, grade, lymph node status and disease-specific survival. RESULTS: CD44 expression was detected in epithelial cells of both intratumoral and normal tissues with different intensities and staining distributions. In normal tissues CD44 protein was mainly detected in cell membranes, whereas in the tumor compartments it was found in both the cell membranes and the cytoplasm. The intensities and percentages of CD44 expressing cells did not correlate with tumor stage and/or grade. Seventy-three percent of the patients with lymph node metastasis showed high intensities of CD44 staining, as compared to 44% of the patients without lymph node metastasis (P = 0.03). Lymph node-positive patients showed both cytoplasmic and membranous CD44 expression. High CD44 expression was found to be significantly correlated with a decreased 5 year overall survival (P = 0.01). CONCLUSIONS: CD44 levels and patterns of expression can be considered as markers for penile SCC aggressiveness and, in addition, may serve as predictive markers for lymph node metastasis, also in patients with clinically negative lymph nodes. CD44 expression may provide prognostic information for penile SCC patients, next to classical clinical-pathological factors.

Pathogenic and Diagnostic Potential of BLCA-1 and BLCA-4 Nuclear Proteins in Urothelial Cell Carcinoma of Human Bladder.

Transitional cell carcinoma (TCC) of the bladder is one of the most common malignancies of genitourinary tract. Patients with bladder cancer need a life-long surveillance, directly due to the relatively high recurrence rate of this tumor. The use of cystoscopy represents the gold standard for the followup of previously treated patients. Nevertheless, several factors, including cost and invasiveness, render cystoscopy not ideal for routine controls. Advances in the identification of specific alterations in the nuclear structure of bladder cancer cells have opened novel diagnostic landscapes. The members of nuclear matrix protein family BLCA-1 and BLCA-4, are currently under evaluation as bladder cancer urinary markers. They are involved in tumour cell proliferation, survival, and angiogenesis. In this paper, we illustrate the role of BLCA-1 and BLCA-4 in bladder carcinogenesis and their potential exploitation as biomarkers in this cancer.