Clinical value of perioperative levels of DNA and mRNA in plasma of patients with renal cell carcinoma.

INTRODUCTION: The current challenge on renal cell carcinoma (RCC) is to finding a non-invasive biomarker for improving their diagnostic and therapeutic management. In the present study, we analyzed the clinical value of plasma levels of cell-free DNA (cfDNA) and RNA (cfRNA) of two genes: glyceraldehyde 3-phosphate-dehydrogenase (GAPDH) and human telomerase reverse transcriptase (hTERT). MATERIALS AND METHODS: We recruited 82 patients with RCC, and 20 healthy subjects. Using RT-PCR techniques, plasma levels of cfDNA and cfRNA from hTERT and GAPDH genes were quantified pre- and post-operatively, and one year after surgery. Relationships between such plasma levels and clinicopathological features and evolution of disease were analyzed. RESULTS: Levels of GAPDH cfDNA and cfRNA were significantly higher in patients than in healthy subjects. hTERT cfDNA was detected in plasma from 35% of RCC patients and in none healthy subject. At diagnosis, plasma levels of GAPDH cfDNA were higher in advanced pT and TNM stages, and hTERT cfDNA in patients with 3-4 Fuhrman grade and affected lymph nodes. Levels of cfNAs were not related to the presence of metastasis. Following nephrectomy, GAPDH cfDNA levels dropped, and patients with higher levels before and after nephrectomy, showed lower overall survival (OS). However, Cox's multivariate model did not prove any association of the cfNA levels with progression. CONCLUSION: Plasma levels of cfDNA from GADPH and hTERT genes were correlated to tumor diagnosis and progression and, thus, such analyses might help to diagnosis and prognosis of RCC patients.

Frailty, physical function and affective status in elderly patients on hemodialysis.

OBJETIVES: To analyze depression, cognition, and physical function change in older adults on hemodialysis at 12-month follow-up, depending on frailty status. DESIGN: Ongoing cohort study. PARTICIPANTS: 117 patients older than 69 years on hemodialysis; 75 men. MEASUREMENTS: Frailty was measured with the frailty phenotype, disability in basic and instrumental activities of daily living with the Barthel and Lawton index respectively, physical function with the Short Physical Performance Battery (SPPB), cognitive status with the Mini Cognitive Examination, and depression with the Yesavage´s Geriatric Depression Scale (GDS), at hemodialysis initiation and after 12-month follow-up. Inflammatory and nutrition profile was determined with C-reactive protein (CRP), albumin, and haemoglobin levels. RESULTS: The mean age of the participants was 78.1 years; 63 (53.8 %) were frail. Frail participants had a higher 12-month mortality risk compared to the non frail ones, hazard ratio 2.6 (95 % CI 0.9-7.9). Frail 12-month survivors presented an improvement in median GDS scores (10 to 9; p = .009). There was no change in frail survivors from SPPB ≤ 6 to SPPB > 6 and a shift in 29.3 % of non-frail survivors from SPPB > 6 to SPPB ≤ 6 (p = .007) after 12-month follow-up. Median CRP and haemoglobin levels improved in frail 12-month survivors from 13.9 to 8.3 mg/dL (p = .019) and 9.9-11.1 g/dL (p < .001) respectively. CONCLUSIONS: Frail older adults that initiate hemodialysis present higher mortality than the non-frail ones at 12-month follow-up. Frail patients that survive improve physical function, depression and inflammatory profile compared to the non frail ones.

Diagnostic and prognostic value of the detection of hTERT mRNA in renal tumors.

INTRODUCTION: Elevated mRNA expression of human telomerase reverse transcriptase (hTERT mRNA) is common in many types of tumors, participating in tumor growth and progression. Such expression has not been sufficiently examined in renal cancer. The goal of the present study was to quantify it and analyze its possible clinical value in the management of this pathology. PATIENTS AND METHODS: The study included 111 patients who underwent surgery for renal cell carcinoma (RCC) between 2015 and 2017. Tumor samples were taken from all patients and, in 94 of them, healthy renal tissue adjacent to the tumor was also sampled. The 2 types of tissue were histologically confirmed, after which mRNA was extracted. Using real-time quantitative PCR, the expression of hTERT and glyceraldehyde-3-phosphate dehydrogenase (as endogenous control) were indirectly quantified using the crossing point (CP), which is inversely correlated with the number of sample replicates yielding positive results. These values were correlated with patient socio-demographic variables and clinical-pathological factors of the RCC. RESULTS: The majority of patients were males, with an average age of 60.5 years (SD: 14.02). Most tumors (69.4%) were clear cell carcinomas. The most frequent stages were pT2 or lower (73%), while 5% were pN1 and 12% pM1. The majority of tumors (58%) were Fuhrman grades 1 or 2 (low grade). All samples of tumor and nontumor tissue expressed glyceraldehyde-3-phosphate dehydrogenase mRNA, with the CP in the tumor sample significantly lower than in the nontumor tissue (P < 0.001). The expression of hTERT mRNA was detected in 68% of tumor tissues and significantly correlated with histopathology: 100% in sarcomatoid RCC and 77.9% in clear cell carcinomas (P < 0.0001). The CP was lower in pN1 (P = 0.018), pM1 (P = 0.046), and TNM IV stages (P = 0,041). A greater number of hTERT mRNA replicas were detected in M1 patients (P = 0.0005) and TNM IV stage (P = 0.017). There was no correlation of hTERT mRNA expression with Fuhrman grade. CONCLUSIONS: The quantitation of hTERT mRNA expression in RCC might be useful as a complementary diagnostic tool as well as for assessing aggressiveness of the tumor.

Autophagic cell death associated to Sorafenib in renal cell carcinoma is mediated through Akt inhibition in an ERK1/2 independent fashion.

OBJECTIVES: To fully clarify the role of Mitogen Activated Protein Kinase in the therapeutic response to Sorafenib in Renal Cell Carcinoma as well as the cell death mechanism associated to this kinase inhibitor, we have evaluated the implication of several Mitogen Activated Protein Kinases in Renal Cell Carcinoma-derived cell lines. MATERIALS AND METHODS: An experimental model of Renal Cell Carcinoma-derived cell lines (ACHN and 786-O cells) was evaluated in terms of viability by MTT assay, induction of apoptosis by caspase 3/7 activity, autophagy induction by LC3 lipidation, and p62 degradation and kinase activity using phospho-targeted antibodies. Knock down of ATG5 and ERK5 was performed using lentiviral vector coding specific shRNA. RESULTS: Our data discard Extracellular Regulated Kinase 1/2 and 5 as well as p38 Mitogen Activated Protein Kinase pathways as mediators of Sorafenib toxic effect but instead indicate that the inhibitory effect is exerted through the PI3K/Akt signalling pathway. Furthermore, we demonstrate that inhibition of Akt mediates cell death associated to Sorafenib without caspase activation, and this is consistent with the induction of autophagy, as indicated by the use of pharmacological and genetic approaches. CONCLUSION: The present report demonstrates that Sorafenib exerts its toxic effect through the induction of autophagy in an Akt-dependent fashion without the implication of Mitogen Activated Protein Kinase. Therefore, our data discard the use of inhibitors of the RAF-MEK-ERK1/2 signalling pathway in RCC and support the use of pro-autophagic compounds, opening new therapeutic opportunities for Renal Cell Carcinoma.

Prognostic Value of the VHL, HIF-1α, and VEGF Signaling Pathway and Associated MAPK (ERK1/2 and ERK5) Pathways in Clear-Cell Renal Cell Carcinoma. A Long-Term Study.

BACKGROUND: The prognostic value of molecular markers in renal cell carcinoma has been investigated in several studies. Although their value is still not confirmed, various proteins are important. We describe the effect on long-term survival of the status of the von Hippel-Lindau (VHL) hypoxia-inducible factor 1-α (HIF1-α) signaling pathway as well as associated mitogen-activated protein kinase (extracellular signal-regulated kinase [ERK]1/2 and ERK5). PATIENTS AND METHODS: A prospective, longitudinal cohort study was conducted with 50 patients diagnosed with clear-cell renal cell carcinoma to analyze VHL mutations and hypermethylation as well as VHL, HIF1-α, vascular endothelial growth factor (VEGF), ERK1/2, and ERK5 protein expression. Overall survival (OS), disease-specific survival (DSS), and progression- or recurrence-free survival (PFS) were analyzed using the Kaplan-Meier method. Mantel-Haenszel was used for comparisons, and Cox proportional risk models were also constructed. RESULTS: Follow-up was 66.9 months. There were 23 (46.0%) deaths, of which 17 (73.9%) were caused by the tumor. Mean periods were 85.6 months for OS and 94.3 months for DSS. A total of 22 (44.0%) patients showed progression (PFS, 78.1 months). VHL expression (P = .045) and > 10% of HIF1-α expression (P = .034) were associated with greater OS. DSS was greater in patients without VHL methylation (P = .012), with > 10% HIF1-α expression (P = .037), or with ERK5 protein underexpression. Greater PFS was associated with absence of VHL methylation (P = .045), presence of VHL expression (P < .0001), HIF1-α expression > 10% (P = .04), and ERK5 protein underexpression (P = .011). The presence of VHL mutation and/or methylation and VEGF expression had no prognostic value. Fuhrman nuclear grade and Tumor, Node, Metastases (TNM) stage were the only variables that remained in the Cox model. CONCLUSION: The HIF1-α and ERK5 pathway has prognostic value. Patients with no VHL or HIF1-α expression and ERK5 overexpression had a worse course of disease. VHL or VEGF status had no prognostic value. Only TNM stage and Fuhrman nuclear grade remained in the Cox model and, therefore, are still essential in prognostic biomarker panels.

VHL promotes immune response against renal cell carcinoma via NF-κB-dependent regulation of VCAM-1.

Vascular cell adhesion molecule 1 (VCAM-1) is an adhesion molecule assigned to the activated endothelium mediating immune cells adhesion and extravasation. However, its expression in renal carcinomas inversely correlates with tumor malignancy. Our experiments in clear cell renal cell carcinoma (ccRCC) cell lines demonstrated that von Hippel Lindau (VHL) loss, hypoxia, or PHD (for prolyl hydroxylase domain-containing proteins) inactivation decreased VCAM-1 levels through a transcriptional mechanism that was independent of the hypoxia-inducible factor and dependent on the nuclear factor κB signaling pathway. Conversely, VHL expression leads to high VCAM-1 levels in ccRCC, which in turn leads to better outcomes, possibly by favoring antitumor immunity through VCAM-1 interaction with the α4ß1 integrin expressed in immune cells. Remarkably, in ccRCC human samples with VHL nonmissense mutations, we observed a negative correlation between VCAM-1 levels and ccRCC stage, microvascular invasion, and symptom presentation, pointing out the clinical value of VCAM-1 levels as a marker of ccRCC progression.

Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis.

OBJECTIVES: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. MATERIAL AND METHODS: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables. A bivariate and multivariate descriptive logistical regression analysis was performed, using the presence of metastasis at diagnosis as dependent variable. RESULTS: The study identified 13 (26%) VHL mutations related to nuclear grade (P = 0.036). VHL hypermethylation was found in 20% of cases. VHL expression was associated with the presence of mutations (P = 0.013), and the absence of expression was associated with nuclear grade and the presence of metastasis (P<0.05). HIF-1alpha was negative in only 5 cases. Vascular endothelial growth factor (VEGF) was positive in 31 of 47 cases and was associated with Fuhrman nuclear grade, presence of metastasis, and stage (P<0.05). ERK5 expression was increased in 58% of cases and associated with the presence of metastasis and more advanced stages (P<0.05). In the logistic regression analysis, the only variable remaining in the model was VEGF expression (P = 0.014). CONCLUSIONS: VEGF has prognostic value in clear cell renal cell carcinoma, and ERK5 may be a new prognostic marker in this type of tumor owing to its relationship with metastasis and more advanced stages.

Metástasis cutánea de carcinoma urotelial de vejiga. Presentación de un caso / Cutaneous metastasis of urothelial carcinoma of the bladder. Case report

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Carbonic anhydrase IX as a specific biomarker for clear cell renal cell carcinoma: comparative study of Western blot and immunohistochemistry and implications for diagnosis.

OBJECTIVE: This study aimed to evaluate the usefulness of carbonic anhydrase IX (CA-IX) expression in clear cell renal cell carcinoma (CCRCC) using two different techniques to detect protein expression. MATERIAL AND METHODS: An experimental, cross-sectional, analytical study was conducted to analyse proteins in renal tumour and healthy tissue specimens from 38 consecutive patients who underwent nephrectomy for renal cancer. CA-IX protein expression was measured by immunohistochemistry and Western blot analysis and quantified. Statistical analysis was performed with the positive and negative specific agreements and kappa coefficient. The sensitivity and specificity of both techniques were assessed. Statistical tests were conducted to analyse the association between CA-IX expression quantitation and normal prognosis factors (TNM stage and Fuhrman nuclear grade), only in CCRCC. RESULTS: The mean patient age was 65 years, 78.9% of patients were men and 57.9% of tumours were CCRCC. CA-IX protein expression was positive in 63.2% of tumours by immunohistochemistry and in 60.5% by Western blot. Both techniques detected CA-IX expression only in CCRCC and unclassifiable tumours. High concordance indices were observed for CCRCC diagnosis. Western blot and immunohistochemistry had a sensitivity of 95.5% and 100%, respectively; the specificity was 100% in both techniques. CA-IX expression quantitation did not correlate with tumour stage or Fuhrman nuclear grade. CONCLUSIONS: Immunochemistry and Western blot techniques can be used to detect abnormal CA-IX protein expression in CCRCC and to support morphology-based diagnostic techniques.

Role of CYP1B1 gene polymorphisms in bladder cancer susceptibility.

PURPOSE: CYP1B1 activates procarcinogens in some human tissues, including the urinary tract. Changes related to genetic polymorphisms are a known risk factor for cancer. We analyzed the association between CYP1B1 sequence variations and bladder cancer. MATERIALS AND METHODS: Sequence variations in the coding region (exons 2 and 3) and the neighboring introns of CYP1B1 were analyzed by direct polymerase chain reaction and DNA sequencing in 208 unrelated patients with bladder cancer and 208 healthy controls. RESULTS: We identified 6 known single nucleotide polymorphisms organized into 2 linkage disequilibrium blocks. The Ala/Ala and Leu/Val genotypes of the Ala119Ser and Leu432Val polymorphisms were significantly more common in patients than in controls (55.3% vs 42.8% and 54.8% vs 42.3%, respectively). The strongest individual single nucleotide polymorphism risk was found under an over dominant model for Leu432Val (OR 1.65, CI 95% 1.12-2.44). The 2 susceptibility single nucleotide polymorphisms were predicted to be structured into 4 haplotypes and more than 10 diplotypes. No individual haplotype was associated with bladder cancer but the diplotype Ala-Leu/Ala-Val was significantly overrepresented in cases compared to controls (31.73% vs 17.31%, OR 2.22, 95% CI 1.36-3.62, p = 0.001). The OR was approximately 1.6 for the individual genotypes Ala/Ala and Leu/Val, which increased to 2.2 for the Ala-Leu/Ala-Val diplotype. A risk occupation had a modifying effect, increasing the crude OR of the combined genotype Ala/Ala + Leu/Val from 2.2 to 8.3. CONCLUSIONS: This study provides strong evidence for the role of common CYP1B1 variants as risk factors for bladder cancer, which increases with occupational exposure.

GSTT1, GSTM1, and CYP1B1 gene polymorphisms and susceptibility to sporadic renal cell cancer.

PURPOSE: To estimate the prevalence and importance of GSTT1, GSTM1, and CYP1B1 genotypes in renal cell carcinoma (RCC), and to identify their value as a prognostic factor. MATERIALS AND METHODS: Cross-sectional study of a group of patients diagnosed with RCC (n = 133) and a control group (n = 208) with benign conditions and no history of tumor. Controls were selected by cumulative samples and mixed pairing. All subjects pertained to the catchment area for our hospital. Sociodemographic variables, anatomical pathology features, and presence of GSTT1, GSTM1, and CYP1B1 polymorphisms by multiplex PCR and sequencing techniques. RESULTS: There were no differences in the genotype distribution of the GSTT1 and GSTM1 genes between cases and controls. In the case of CYP1B1, the GG genotype (Ala119) was more prevalent in patients with RCC (OR = 2.08; 95% CI: 1.32-2.28) and may be implicated in 34.3% (95% CI: 16.3-52.2) of RCCs. In patients with GSTT1 deletion, TNM stages III to IV were more common (39.1%); whereas in Val432 homozygous patients in CYP1B1, Fuhrman grades 3 to 4 (54.6%) were more common. Because this was a cross-sectional study, longitudinal studies are needed in the future to confirm these data. CONCLUSIONS: No relationship between GSTT1 and GSTM1 genotypes and RCC risk was observed. Homozygous subjects with Ala119 in CYP1B1 had twice the risk of RCC as homozygous for Ser119 or heterozygotes. Patients with GSTT1 deletion had tumors of more advanced stages, and those with Val432 polymorphism in CYP1B1 had tumors of higher Fuhrman grade.

Vesical nephrogenic adenoma: an unusual presentation of a bladder tumour.

Vesical nephrogenic adenoma is a rare, benign entity that appears most commonly in middle-aged males. Its etiology is unknown, but it has been linked to chronic irritating factors, such as infection, trauma, urological surgery, kidney stones, foreign bodies and chemical agents, such as Bacille Calmette-Guerin. We report 2 new cases with a history of transurethral resection of the bladder and the prostate and a history of prolonged voiding symptoms. In both cases, the findings of encysted tubular structures lined with flattened cuboidal cells without atypia were consistent with the diagnosis of vesical nephrogenic adenoma.

Polymorphic deletions of the GSTT1 and GSTM1 genes and susceptibility to bladder cancer.

UNLABELLED: What's known on the subject? and What does the study add? Bladder cancer susceptibility may be determined by genetic differences in the activity of glutathione S-transferases, enzymes that regulate the conversion of exogenous carcinogens to excretable hydrophilic metabolites by glutathione conjugation. The discrepancy of results regarding the association of common genetic polymorphisms and complex diseases such as cancer has raised scepticism in this area of research. Although the evidence generally supports the implication of GSTM1 and GSTT1 polymorphisms in bladder cancer, there is still some debate, with some studies in favour and some against. This study shows a greater risk of bladder cancer in individuals with GSTM1 null genotype, particularly women. This relationship is less evident with GSTT1 null genotypes. Null genotypes in both genes appear to be synergistic, particularly among smokers, and to increase the predisposition to more aggressive tumours. Nevertheless, the role of GSTM1 and GSTT1 polymorphisms in predisposition to bladder cancer should be viewed with caution, due to the multifactorial genetic origin of this condition and the need for long-term longitudinal studies to confirm these results. OBJECTIVE: To estimate the prevalence and importance of GSTT1 and GSTM1 genotypes (implicated in glutathione S-transferase activity) in bladder cancer, to determine whether smoking and occupational factors influence this relationship, and to identify the value of GSTT1 and GSTM1 genotypes as prognostic factors. PATIENTS AND METHODS: A cross-sectional study was conducted with a group of patients with bladder carcinoma and a control group with benign conditions and no history of tumours. The controls were selected and paired as subjects were recruited. Sociodemographic variables, smoking, professional occupation, histological features and the presence of GSTT1 and GSTM1 polymorphisms by multiplex PCR techniques were assessed. RESULTS: GSTM1 genotypes were investigated in 201 patients and 193 controls and GSTT1 genotypes in 190 patients and 163 controls. In the patients group, GSTT1 null genotype was observed in 22.1% (not significant) and GSTM1 null genotype in 54.2% (P=0.008) (odds ratio, OR, 1.7); when considered together, 15.5% (P<0.05; OR, 3.5) of patients had both null genotypes. In the multivariate analysis, the presence of GSTM1 null genotype remained in the model (OR, 2.1) in addition to smoking and age. Subjects with bladder tumour and GSTM1 null genotype were younger than patients without gene deletion (P=0.049). Women with GSTM1 null genotype presented a higher OR than men (P=0.024). When stratified by smoking habit, smokers with both null genotypes showed an OR of 4.7. The percentage of patients with G3 tumours was higher in patients with GSTT1 null genotype (P=0.013) and in patients with both null genotypes (P=0.002). A higher percentage of infiltrating tumours was also observed in patients with both null genotypes (P=0.035). CONCLUSIONS: The data obtained in the present study suggest a higher risk of bladder cancer in individuals with the GSTM1 null genotype. This risk is twofold higher when GSTM1 and GSTT1 null genotypes are both present and is also higher in smokers. A greater predisposition for more aggressive tumours appears to exist, particularly when both null genotypes are combined. Longer-term longitudinal studies are needed to confirm these results.

Implications of p53 gene mutations on patient survival in transitional cell carcinoma of the bladder: a long-term study.

OBJECTIVE: To determine the prognostic value of p53 gene mutations and P53 overexpression for predicting the incidence of recurrence, progression and long-term survival of patients with transitional cell carcinoma (TCC) of the bladder. METHODS: Prospective cohort study with 94 consecutive patients diagnosed and treated for TCC. DNA was obtained from tumor tissue to perform PCR-SSCP of p53 exons 5-9, with automatic sequencing of any mutated samples. Immunohistochemistry using anti-human P53 monoclonal antibody was also performed. Survival was analyzed and the survival curves compared (Mantel-Haenszel). Lastly, a Cox proportional hazards model was constructed. RESULTS: Mutations were found in 46.8% of samples, with 61.8% in infiltrating tumors. Exon 8 was involved in 42.3%. P53 overexpression (cutoff > or =20%) was found in 52.1%. Mean follow-up was 44.1 months; 43.6% had died by the end of this period. Mean survival was lower in patients with exon 8 mutations (38.4 months), compared with patients without this exon mutated (P = 0.016). There were no differences in patient survival based on positive or negative immunohistochemistry (cutoff > or =20%), although survival was lower in patients with a percentage higher than 50% of antibody-stained cells (P = 0.02). In the Cox analysis, tumor stage, pM stage, and interaction between stage > or =pT2 and mutated p53 gene were independent risk factors, with a 6.13-fold risk of death in these patients (P = 0.019). The number of tumors, nuclear grade, pTa stage, and the interaction between GI degree and nonmutated p53 gene remained in the Cox model for superficial tumors, such that these patients had a lower risk of recurrence or progression (P = 0.008). CONCLUSIONS: Alterations in the p53 gene may be indicative of poorer prognosis and greater recurrence in patients with urothelial bladder tumor, in particular, the presence of mutations in exon 8 and a greater percentage of stained cells in the immunohistochemistry. Nevertheless, the classic prognostic factors (primarily, pTNM stage) should still be considered the most useful factors for follow-up of these patients.

Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma.

OBJECTIVES: To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC). MATERIALS AND METHODS: Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed. RESULTS: MSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms. CONCLUSIONS: Our data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC.

Sensitivity and specificity of p53 protein detection by immunohistochemistry in patients with urothelial bladder carcinoma.

OBJECTIVE: To analyze the correlation between the genotypic and phenotypic patterns of p53 in patients with transitional cell carcinoma (TCC) of the urinary bladder. MATERIALS AND METHODS: Cross-sectional study of 73 patients diagnosed with TCC. DNA was obtained from the tumor tissue to perform polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) of exons 5-9 of the p53 gene, with automatic sequencing done on any mutated samples. Immunohistochemistry (IHC) was also performed using anti-human P53 monoclonal antibody, and the diagnostic performance of this test was analyzed by a ROC curve, using the presence of p53 mutations found by PCR-SSCP as 'gold standard'. RESULTS: The cutoff point for defining immunopositivity was 20%. IHC had a specificity of 62.9%, and a sensitivity of 65.8%. The highest sensitivity values appeared in G3 tumors (75%) and infiltrating tumors (71.4%), and the highest specificity values were observed in G1 (77.7%) and G2 tumors (90%) and superficial tumors (66.6%). Mutations in exon 8 gave a positive result most frequently (73.7%) and were considered most relevant in terms of altering P53 function (60.9%). False negatives were documented in 28.5% of infiltrating tumors, and false positives in 33.4% of superficial tumors. CONCLUSIONS: There is a moderate correlation between p53 mutations and P53 protein overexpression, with this stronger in high-grade, infiltrating tumors, in exon 8 mutations, and when the mutation induces relevant changes in the protein structure. Although IHC is useful in routine clinical practice, the classic prognostic factors should still be considered the most important in the follow-up of these patients.

Update on the diagnosis and treatment of bladder endometriosis.

Bladder endometriosis is rare, although the bladder is the urinary tract structure most often affected by this condition. The common clinical manifestations of bladder endometriosis include menouria and urethral and pelvic pain syndrome occurring cyclically. Imaging methods are not conclusive for the definitive diagnosis. Cystoscopy is the most useful diagnostic test with confirmation by histologic study. Treatment must be individualized according to the patient's age, desire for future pregnancies, the severity of the symptoms, the site affected, and whether other organs are involved. Two types of treatment are currently used as follows: medical-hormonal and surgical.