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1.
Diagn Pathol ; 16(1): 106, 2021 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-34801034

RESUMEN

INTRODUCTION: Microsatellite instability occurs due to a series of mutations in the DNA pairing error repair (Mismatch repair; MMR) genes, which can affect germ cells as occurs in Lynch syndrome, whose patients are at high risk of developing multiple cancers. The loss of MMR protein is commonly determined by immunohistochemical studies. Although the relation between microsatellite instability and urothelial carcinomas has been widely studied, its evaluation is not currently performed in the analysis of urothelial carcinomas. METHODS: In this study, the microsatellite status of 139 urothelial carcinomas was analyzed and their clinicopathological characteristics were evaluated. We identified that 10.3% (13 patients) of urothelial carcinomas had loss of MMR protein expression (9 MLH1; 5 MSH2; 2 PMS2; 2 PSH6; n = 139). RESULTS: Results suggest that these tumors occur more frequently in males, are more frequently located in the bladder or ureters, and present a high tumor grade with a papillary histological pattern that does not infiltrate the lamina propria or, in the case of infiltrating tumors, that grows into perivesical tissues. CONCLUSIONS: We identified patients with the aforementioned tumor characteristics as patients with a high probability of presenting loss of MMR protein expression, and consider that only these patients should undergo further immunohistochemical and molecular techniques for proper diagnosis. Therefore, we propose that the clinicopathological characteristics found in the present study could become possible markers to determine which cases should undergo additional tests.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Enzimas Reparadoras del ADN/genética , Inestabilidad de Microsatélites , Neoplasias Urológicas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Carcinoma/química , Carcinoma/patología , Niño , Preescolar , Enzimas Reparadoras del ADN/análisis , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/análisis , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Homólogo 1 de la Proteína MutL/análisis , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/análisis , Proteína 2 Homóloga a MutS/genética , Clasificación del Tumor , Estadificación de Neoplasias , Fenotipo , Neoplasias Urológicas/química , Neoplasias Urológicas/patología , Urotelio/química , Urotelio/patología , Adulto Joven
2.
Future Oncol ; 17(31): 4145-4156, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34467778

RESUMEN

Background: Bioinformatic analysis has revealed that OXR1 is significantly downregulated in muscle-invasive bladder cancer. Patients & methods: The expression of OXR1 in patients with urothelial carcinoma was evaluated by immunohistochemistry, including 340 cases with urothelial carcinoma in the upper urinary tract and 295 in the urinary bladder. Results: Low expression of OXR1 was significantly correlated with adverse pathological parameters including high primary tumor (pT) stage, high node stage, high histological grade, high mitotic activity and increased vascular or perineural invasion (all p < 0.05). Low expression of OXR1 independently predicted worse metastasis-free survival (p = 0.033) in urothelial carcinoma of the upper urinary tract and worse disease-specific survival (p = 0.022) and metastasis-free survival (p < 0.001) in urothelial carcinoma of the urinary bladder. Conclusion: Low expression of OXR1 is an adverse prognostic factor in urothelial carcinoma.


Asunto(s)
Carcinoma de Células Transicionales/mortalidad , Proteínas Mitocondriales/análisis , Neoplasias Urológicas/mortalidad , Adulto , Anciano , Carcinoma de Células Transicionales/química , Carcinoma de Células Transicionales/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias Urológicas/química , Neoplasias Urológicas/patología
3.
Hum Pathol ; 113: 1-8, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33887303

RESUMEN

Noninvasive low-grade papillary urothelial carcinoma is a papillary neoplasm with orderly appearance and mild nuclear pleomorphism. Some cases show significant nuclear pleomorphism with degenerative atypia leading to grading difficulties. A retrospective review of the pathology files identified 16 cases diagnosed as noninvasive low-grade papillary urothelial carcinoma with degenerative atypia. Fifteen cases were consults. The average age was 46 years (range 19-78). The average size was 1.7 cm (range: 0.3-3.5). The submitting diagnoses in consults were noninvasive high-grade papillary urothelial carcinoma (n = 6), condyloma (n = 1), atypical papillary lesion (n = 1), prominent umbrella cells (n = 1), and not given (n = 6). Ki-67 proliferation rate was <5% in 10 of 10 cases (100%), and the cells with large atypical nuclei were negative. Microscopically, there were scattered cells with nuclei larger than 5 times the size of stromal lymphocytes but displayed smudgy chromatin and occasional multinucleation and intranuclear vacuoles. Next-generation sequencing identified the following mutations: HRAS (n = 4), FGFR3 (n = 3), KRAS (n = 3), BRAF (n = 1), PDGFRA (n = 1), and PIK3CA (n = 1). Other deleterious mutations were identified, but none in genes characteristic of high-grade tumors. Follow-up was available in 6 patients (median 32 months). One patient recurred with a noninvasive low-grade papillary urothelial carcinoma 20 months after the index case. All the remaining patients had no evidence of disease at the last follow-up. No patient died or had disease progression. The combination of preservation of polarity, low mitotic activity, Ki-67 <5% with the larger atypical nuclei negative for Ki-67, along with nuclear atypia that is degenerative are features used to classify these tumors as low grade.


Asunto(s)
Carcinoma Papilar/patología , Núcleo Celular/patología , Neoplasias Urológicas/patología , Urotelio/patología , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma Papilar/química , Carcinoma Papilar/genética , Núcleo Celular/química , Proliferación Celular , Análisis Mutacional de ADN , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Índice Mitótico , Mutación , Clasificación del Tumor , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Neoplasias Urológicas/química , Neoplasias Urológicas/genética , Urotelio/química , Adulto Joven
4.
Am J Clin Pathol ; 154(6): 802-810, 2020 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-32864684

RESUMEN

OBJECTIVES: Persistent antigen exposure leads to the accumulation of lymphocytes and subsequent tertiary lymphoid structures (TLS). We investigated the relationship of tumor microenvironment (TME) with respect to programmed death ligand 1 (PD-L1), its receptor programmed death 1 (PD-1), and TLS in upper tract urothelial carcinoma (UTUC) cases and compared them with UTUC associated with urothelial bladder carcinoma (UTUC-BCa). METHODS: We retrospectively identified 72 patients with UTUC. Representative slides were reviewed, and TLS were counted. Immunohistochemical stains for PD-1 and PD-L1 were performed. PD-1-positive lymphocytes were counted and H-score for PD-L1-positive membranous staining was determined. RESULTS: PD-L1 expression in the tumor was present in 55.1% of the UTUC cases. Higher stage was associated with increased PD-L1 expression (P = .035). TLS were present in 33.3% and their presence was significantly associated with PD-L1 positivity (P = .024). This association remained significant after adjustment for UTUC-BCa. TLS were also associated with a greater number of infiltrating PD-1-positive lymphocytes (P = .013). CONCLUSIONS: This study is one of the first comparative studies of the TME in UTUC and UTUC-BCa. PD-L1 is expressed in a subset of UTUC and is associated with TLS. The presence of TLS is an inherent characteristic of UTUC and not secondary to the presence of BCa.


Asunto(s)
Antígeno B7-H1/análisis , Linfocitos/patología , Neoplasias Urológicas/química , Neoplasias Urológicas/patología , Anciano , Femenino , Humanos , Inmunohistoquímica , Masculino , Receptor de Muerte Celular Programada 1/análisis , Estudios Retrospectivos , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patología
5.
Am J Clin Pathol ; 154(6): 792-801, 2020 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-32789450

RESUMEN

OBJECTIVES: Universal screening of upper tract urothelial carcinoma (UTUC) for Lynch syndrome by mismatch repair (MMR) protein immunohistochemistry (IHC) has been recommended by some investigators. Herein, we assess this recommendation retrospectively by simulating its performance on a retrospective, unselected cohort of UTUCs, with comparison to the established setting of colorectal and endometrial adenocarcinoma. METHODS: We assessed for complete loss of MMR protein (MLH1, MSH2, MSH6, and PMS2) IHC in 74 consecutive cases of UTUC and then tabulated clinical and pathologic factors. MMR findings from same-institution colorectal and endometrial adenocarcinomas were tabulated for comparison. RESULTS: We observed loss of at least one MMR protein in 12% in our UTUC cohort (three MSH2/MSH6, three MSH6 only, one MLH1/PMS2, and two PMS2 only). Of these nine cases (seven males, two females, median age 67 years, five associated with colorectal adenocarcinoma), at least three (4% of the overall cohort) proved to be Lynch syndrome. Overall, MMR loss in UTUC was comparable to colorectal (11%; 50 of 471 cases) and endometrial (12%; 12 of 101 cases) adenocarcinomas. CONCLUSIONS: The rate of MMR loss observed in UTUC was comparable to that in the established setting of colorectal and endometrial adenocarcinomas, supporting universal UTUC screening at our institution and others.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Reparación de la Incompatibilidad de ADN , Neoplasias Urológicas/química , Adenocarcinoma/química , Anciano , Neoplasias Colorrectales/química , Proteínas de Unión al ADN/análisis , Neoplasias Endometriales/química , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/análisis , Homólogo 1 de la Proteína MutL/análisis , Proteína 2 Homóloga a MutS/análisis , Estudios Retrospectivos , Neoplasias Urológicas/patología , Urotelio/patología
6.
Am J Clin Pathol ; 151(6): 561-573, 2019 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-30776071

RESUMEN

OBJECTIVES: Limited literature is available on the tumor microenvironment (TM) of upper tract urothelial carcinoma (UTUC). This study comprehensively reviews programmed death 1 receptor (PD-1)-positive and CD8+ tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on tumor epithelium (TE). METHODS: Seventy-two nephroureterectomy specimens were analyzed for PD-L1, PD-1, and CD8. One percent or more tumor and lymphohistiocyte PD-L1 expression was considered positive. TIL density by H&E was scored semiquantitatively from 0 to 3, and CD8+ and PD-1+ TILs were quantified in hotspots. RESULTS: Of the cases, 37.5% demonstrated PD-L1+ on TE. PD-L1+ TE showed an association with pathologic stage (P = .01), squamous differentiation (SqD) (P < .001), TILs by H&E (P = .02), PD-1+ peritumoral TILs (P = .01), and PD-L1+ peritumoral lymphohistiocytes (P = .002). Finally, there was a significant difference in PD-1+ peritumoral TILs in cases with SqD vs no SqD (P = .03). CONCLUSIONS: Aggressive UTUC is associated with a distinct TM. Furthermore, TM of UTUC-SqD was distinctly different from those with no SqD, warranting study in a larger cohort.


Asunto(s)
Antígeno B7-H1/análisis , Carcinoma/patología , Neoplasias Urológicas/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/química , Diferenciación Celular , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Microambiente Tumoral , Neoplasias Urológicas/química , Urotelio/patología
7.
Diagn Pathol ; 13(1): 47, 2018 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-30041679

RESUMEN

BACKGROUND: Several anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) therapies have shown encouraging safety and clinical activity in a variety of tumor types. A potential role for PD-L1 testing in identifying patients that are more likely to respond to treatment is emerging. PD-L1 expression in clinical practice is determined by testing one tumor section per patient. Therefore, it is critical to understand the impact of tissue sampling variability on patients' PD-L1 classification. METHODS: Resected non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) and urothelial carcinoma (UC) tissue samples (five samples per tumor type) were obtained from commercial sources and two tumor blocks were taken from each. Three sections from each block (~ 100 µm apart) were stained using the VENTANA PD-L1 (SP263) assay, and scored based on the percentage of PD-L1-staining tumor cells (TCs) or tumor-infiltrating immune cells (ICs) present. Each section was categorized as PD-L1 high or low/negative using a variety of cut-off values, and intra-block and intra-case (between blocks of the same tumor) concordance (overall percentage agreement [OPA]) were evaluated. An additional 200 commercial NSCLC samples were also analyzed, and intra-block concordance determined by scoring two sections per sample (≥70 µm apart). RESULTS: Concordance in TC PD-L1 classification was high at all applied cut-offs. Intra-block and intra-case OPA for the 15 NSCLC, HNSCC or UC samples were 100% and 80-100%, respectively, across all cut-offs; intra-block OPA for the 200 NSCLC samples was 91.0-98.5% across all cut-offs. IC PD-L1 classification was less consistent; intra-block and intra-case OPA for the 15 NSCLC, HNSCC or UC samples ranged between 70 and 100% and between 60 and 100%, respectively, with similar observations in the intra-block analysis of the 200 NSCLC samples. CONCLUSIONS: These results show the reproducibility of TC PD-L1 classification across the depth of the tumor using the VENTANA PD-L1 (SP263) assay. Practically, this means that treatment decisions based on TC PD-L1 classification can be made confidently, following analysis of one tumor section. Although more variable than TC staining, consistent IC PD-L1 classification was also observed within and between blocks and across cut-offs.


Asunto(s)
Antígeno B7-H1/análisis , Carcinoma de Pulmón de Células no Pequeñas/química , Inmunohistoquímica , Neoplasias Pulmonares/química , Adhesión en Parafina , Juego de Reactivos para Diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/química , Neoplasias Urológicas/química , Urotelio/química , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Microtomía , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Neoplasias Urológicas/patología , Neoplasias Urológicas/cirugía , Urotelio/patología , Urotelio/cirugía
8.
Pathol Res Pract ; 213(7): 831-835, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28554748

RESUMEN

BACKGROUND: Nephrogenic adenoma is an uncommon benign lesion that occurs at several sites in urinary tract, from the renal pelvis to urethra, with the highest frequency in urinary bladder. Nephrogenic adenoma displays a broad spectrum of architectural and cytological features. Hence, recognition of its characteristic histopathological features is needed to distinguish this lesion from its mimickers. MATERIALS AND METHODS: A retrospective series of 21 cases of nephrogenic adenoma in 18 patients, which were diagnosed in our department between 2010 and 2016, were analyzed. All histological slides were reviewed by two pathologists and the diagnosis of each case was confirmed. Immunohistochemistry was performed for PAX-8 in all cases. CK7, PAX-2, PSA, p53, p63, GATA-3 and α-methylacyl-CoA racemase (AMACR) were applied in problematic cases. RESULTS: The most common location of the lesion was urinary bladder (14 patients) followed by renal pelvis (2 patients), ureter (1 patient) and urethra (1 patient). A history of urothelial carcinoma and repeated TUR procedures were observed in 12 patients. There were 2 pediatric patients aged 3 years. Both of them had undergone previous urosurgery because of megaureter in one and bladder exstrophy in the other. Other clinical antecedents included bladder diverticulum (1 patient), cystitis (1 patient) and nephrolithiasis (1 patient). Recurrence of lesion was seen in two patients (once in one case and twice in the other one). The median time to disease recurrence in these patients was 11 months (range, 2-20 months). Histologically, the lesions exhibited various morphological findings, with mixed (15 cases, 71.4%), pure tubular (3 cases, 14.3%), pure papillary (2 cases, 9.5%) and pure flat (1 case, 4.8%) growth patterns. Of the 15 cases with mixed patterns, 8 cases were tubulocystic and flat, 3 cases were tubular and flat, 2 cases were tubular, papillary and flat, 1 case was tubulocystic, papillary and flat, and 1 case was tubular and papillary. Flat pattern was observed in 15 cases (71.4%). It was seen in association with other patterns in 14 cases (mixed morphology) and purely in 1 case. Our findings suggested that the flat pattern is a frequent finding in nephrogenic adenomas. Notably one case in this series showed superficial extension into bladder muscularis propria. CONCLUSIONS: Histologically nephrogenic adenoma may simulate a variety of malignancies. Awareness of characteristic morphologic features of nephrogenic adenoma is needed to diagnose this lesion correctly.


Asunto(s)
Adenoma , Neoplasias Urológicas , Adenoma/química , Adenoma/patología , Adenoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Turquía , Neoplasias Urológicas/química , Neoplasias Urológicas/patología , Neoplasias Urológicas/cirugía , Adulto Joven
9.
Ann Pathol ; 36(4): 275-8, 2016 Aug.
Artículo en Francés | MEDLINE | ID: mdl-27474530

RESUMEN

The most important criterion for optimal cancer treatment is a correct classification of the tumour. During the last three years, several very important progresses have been made with a better definition of urothelial carcinoma (UC), especially from a molecular point of view. We start having a global understanding of UC, although many details are still not completely understood.


Asunto(s)
Carcinoma de Células Transicionales/clasificación , Patólogos , Neoplasias Urológicas/clasificación , Biomarcadores de Tumor/análisis , Carcinoma Papilar/química , Carcinoma Papilar/clasificación , Carcinoma Papilar/patología , Carcinoma de Células Transicionales/química , Carcinoma de Células Transicionales/patología , Humanos , Invasividad Neoplásica , Proteínas de Neoplasias/análisis , Neoplasias Urológicas/química , Neoplasias Urológicas/patología , Urotelio/patología , Organización Mundial de la Salud
10.
Mol Biosyst ; 11(6): 1594-602, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25739956

RESUMEN

Bladder cancer is estimated to be the ninth most common malignancy with a high rate of recurrence and progression despite therapy, early diagnosis being crucial for timely intervention. Using a well-established animal model of urothelial carcinoma, we performed a comprehensive analysis of urine proteome profile from healthy animals and animals with urothelial carcinoma at two time-points of disease pathogenesis. GeLC-MS/MS, followed by bioinformatics analysis of unique proteins and the ones present in significantly distinct levels among groups, highlighted the biological processes involved in disease pathogenesis such as, for instance, response to selenium and to drugs, neutral lipid metabolism at earlier stages of disease, and inflammation, immune response and wound healing at advanced stages. Proteins from up-regulated biological processes might be seen as putative disease biomarkers. These include, for example, cadherins, lipoproteins, and glysosyltransferases, which may be included in multimarker strategies. Taken together, the data support the application of urine proteomics for the identification of the biological processes modulated by bladder cancer in an integrative perspective. The present exploratory urinary proteomic analysis might be seen as an important starting point for studies targeting urinary proteins in human, aiming at the implementation of novel laboratory approaches for the detection and successful management of urothelial carcinoma.


Asunto(s)
Biomarcadores/orina , Proteoma/análisis , Neoplasias Urológicas/orina , Animales , Biomarcadores/química , Butilhidroxibutilnitrosamina , Femenino , Proteínas/análisis , Proteínas/química , Proteínas/clasificación , Proteoma/química , Proteoma/clasificación , Ratas , Ratas Wistar , Neoplasias Urológicas/inducido químicamente , Neoplasias Urológicas/química , Urotelio/química , Urotelio/efectos de los fármacos
11.
Urol Int ; 94(1): 50-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25171290

RESUMEN

OBJECTIVE: To conduct a meta-analysis examining p53 expression as a potential risk factor in upper urinary tract urothelial carcinoma (UUT-UC) and to systematically review the available data. METHODS: A comprehensive literature review was performed from January 1991 to August 2012, using search engines such as PubMed, EMBASE, Cochrane Library and KoreaMed. All retrieved references were manually reviewed, and two authors independently extracted the data. The quality of case-control and cohort studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) checklists. Heterogeneity among studies was examined using the Q statistics and Higgins' I(2) statistic. RESULTS: Of 302 abstracts of original research studies, nine case-control trials fit our criteria for inclusion in the analysis. Of the nine articles included, four scored 'low' and five scored 'modest' in the quality assessment performed according to the SIGN checklists. Analysis of the correlation between different factors and p53 expression in UUT-UC showed that pathologic stage (≥pT3 or

Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma/química , Proteína p53 Supresora de Tumor/análisis , Neoplasias Urológicas/química , Urotelio/química , Carcinoma/patología , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores Sexuales , Regulación hacia Arriba , Neoplasias Urológicas/patología , Urotelio/patología
12.
Int J Clin Exp Pathol ; 7(2): 699-708, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24551292

RESUMEN

Upper urinary tract urothelial carcinomas (UUTUC) are infrequent and show an occurrence of about 5-10% of all urothelial carcinomas. In this study, we investigated the HER2 status of 171 UUTUC patients with nephroureterectomy. The number of patients is the largest of any HER2 study. All 171 cases were analyzed for both HER2 overexpression using immunohistochemistry and HER2 gene amplification using dual-color in situ hybridization. The scoring system proposed by the ASCO/CAP and ToGA trials was used. Out of 171 patients, 140 patients had a HER2 score-0 or score-1 (81.9%), 17 a score-2 (9.9%), and 14 a score-3 (8.2%) with immunohistochemistry. HER2 gene amplification was observed in 31 out of 171 cases (18.1%). A good correlation was observed between protein overexpression and gene amplification (p<0.0001). Twenty-three UUTUC (13.5%) were determined as HER2-positive cancer according to ASCO/CAP and ToGA criteria. HER2 positivity in patients over 70 years old was higher than that of patients under 70 years old (p=0.0132). HER2 expression correlated to a high histological grade (p=0.0003) and the coexistence of a high grade carcinoma in situ (p=0.0089). No HER2-positive cancer was observed in patients with renal pelvic UUTUC (0 out of 76, p<0.0001). HER2-positive UUTUC showed a shorter recurrence time in the residual urinary bladder after nephroureterectomy with Kaplan-Meier analysis (p=0.0284) and multivariate analysis (p=0.0034). The results suggest that HER2 positivity in UUTUC is an independent predictive marker for early recurrence of urothelial carcinoma in the residual urinary bladder after surgery.


Asunto(s)
Biomarcadores de Tumor , Carcinoma/química , Carcinoma/genética , Amplificación de Genes , Receptor ErbB-2 , Neoplasias Urológicas/química , Neoplasias Urológicas/genética , Urotelio/química , Factores de Edad , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Carcinoma/patología , Carcinoma/cirugía , Distribución de Chi-Cuadrado , Femenino , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación in Situ , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Fenotipo , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Receptor ErbB-2/análisis , Receptor ErbB-2/genética , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Neoplasias Urológicas/patología , Neoplasias Urológicas/cirugía , Urotelio/patología
13.
Urologia ; 80(1): 29-41, 2013.
Artículo en Italiano | MEDLINE | ID: mdl-23504867

RESUMEN

The future approach of diagnostic imaging in urology follows the technological progress, which made the visualization of in vivo molecular processes possible. From anatomo-morphological diagnostic imaging and through functional imaging molecular radiology is reached. Based on molecular probes, imaging is aimed at assessing the in vivo molecular processes, their physiology and function at cellular level. The future imaging will investigate the complex tumor functioning as metabolism, aerobic glycolysis in particular, angiogenesis, cell proliferation, metastatic potential, hypoxia, apoptosis and receptors expressed by neoplastic cells. Methods for performing molecular radiology are CT, MRI, PET-CT, PET-MRI, SPECT and optical imaging. Molecular ultrasound combines technological advancement with targeted contrast media based on microbubbles, this allowing the selective registration of microbubble signal while that of stationary tissues is suppressed. An experimental study was carried out where the ultrasound molecular probe BR55 strictly bound to prostate tumor results in strong enhancement in the early phase after contrast, this contrast being maintained in the late phase. This late enhancement is markedly significant for the detection of prostatic cancer foci and to guide the biopsy sampling. The 124I-cG250 molecular antibody which is strictly linked to cellular carbonic anhydrase IX of clear cell renal carcinoma, allows the acquisition of diagnostic PET images of clear cell renal carcinoma without biopsy. This WG-250 (RENCAREX) antibody was used as a therapy in metastatic clear cell renal carcinoma. Future advancements and applications will result in early cancer diagnosis, personalized therapy that will be specific according to the molecular features of cancer and leading to the development of catheter-based multichannel molecular imaging devices for cystoscopy-based molecular imaging diagnosis and intervention.


Asunto(s)
Diagnóstico por Imagen/métodos , Técnicas de Diagnóstico Urológico/tendencias , Enfermedades Urológicas/diagnóstico , Diagnóstico por Imagen/tendencias , Predicción , Humanos , Imagen Molecular/métodos , Imagen Molecular/tendencias , Imagen Multimodal/tendencias , Enfermedades Urológicas/metabolismo , Neoplasias Urológicas/irrigación sanguínea , Neoplasias Urológicas/química , Neoplasias Urológicas/diagnóstico
14.
Mod Pathol ; 26(6): 792-8, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23328975

RESUMEN

Nephrogenic adenoma is a benign lesion of the urinary tract, particularly the urinary bladder. It is a gross and microscopic mimicker of urothelial neoplasm or metastatic carcinoma. Several histological patterns (tubular, tubulocystic, polypoid, papillary, fibromyxoid) have been recognized, but a flat pattern has not been described. Histologically, nephrogenic adenoma consists of tubules, cysts or papillae lined by flat to polygonal cells with frequent hobnail appearance. The stroma is often edematous or has a granulation tissue-like appearance with acute or chronic inflammation. By immunohistochemistry, nephrogenic adenomas are positive for renal epithelial markers CK7, CD10 and alpha-methylacyl-coenzyme A racemase, and negative for bladder urothelium or prostate markers. Recent studies have shown that nephrogenic adenomas are positive for PAX2 and PAX8. We encountered an interesting case of tubular nephrogenic adenoma with adjacent areas suspicious of flat urothelial atypia. Immunohistochemistry for PAX2 and PAX8 were positive in these areas, unveiling a flat pattern of nephrogenic adenoma. This case prompted us to study 15 cases of nephrogenic adenoma to determine additional instances of flat pattern and to assess the value of PAX2 and PAX8 immunoreactivity to diagnose nephrogenic adenoma. PAX2 and PAX8 immunostaining was positive in 14/15 and 15/15 cases, respectively. The flat pattern was present at least focally adjacent to tubular, polypoid and papillary areas, in 8/15 cases of nephrogenic adenoma. In conclusion, the flat pattern is a common finding in nephrogenic adenomas, but easily under recognized by morphologic examination and may be confused with flat urothelial lesions with atypia. Immunostains for PAX2 and PAX8 are useful in the detection of nephrogenic adenomas and particularly unveil those nephrogenic adenomas with flat pattern.


Asunto(s)
Adenoma/química , Biomarcadores de Tumor/análisis , Inmunohistoquímica , Factor de Transcripción PAX2/análisis , Factores de Transcripción Paired Box/análisis , Neoplasias Urológicas/química , Adenoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor de Transcripción PAX8 , Valor Predictivo de las Pruebas , Neoplasias Urológicas/patología , Adulto Joven
15.
Nat Rev Urol ; 8(9): 516-22, 2011 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-21811225

RESUMEN

The management of upper urinary tract urothelial carcinoma (UUT-UC) is controversial. Radical nephroureterectomy is a major undertaking and has obvious shortcomings in the presence of renal impairment and solitary kidneys, whereas endoscopic management can be associated with a risk of disease progression. There is a pressing need for reliable predictive biomarkers to refine patient selection for renal conservation. p53 is the most frequently investigated molecular marker in UUT-UC. Of the 24 papers published on the subject, expression of p53 is a significant univariate prognostic marker in 12 publications, representing seven unique cohorts. However, multivariate analysis demonstrates that p53 expression is of independent prognostic significance in only five studies, all of which contain potential statistical bias. The currently available data do not, therefore, support a role for p53 in this regard, and suggest a need for prospective large-scale collaborative studies using standardized methods of p53 detection and statistical analysis.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Regulación Neoplásica de la Expresión Génica , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética , Neoplasias Urológicas/química , Neoplasias Urológicas/genética , Urotelio/patología , Animales , Biomarcadores de Tumor/química , Femenino , Humanos , Masculino , Neoplasias Urológicas/patología , Urotelio/química , Urotelio/metabolismo
16.
Diagn Pathol ; 6: 67, 2011 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-21777423

RESUMEN

BACKGROUND: Distinguishing urothelial carcinoma (UC) from prostate carcinoma (PC) is important due to potential therapeutic and prognostic implications. However, this can be a diagnostic challenge when there is limited tissue and in poorly differentiated tumors. We evaluated the diagnostic utility of a dual immunohistochemical stain comprising p63 and P501S (prostein), applied sequentially on a single slide and visualized by double chromogen reaction, in differentiating these two cancers. Thus far, there have been no previous studies assessing the diagnostic utility of p63 and P501S combined together as a dual immunostain in distinguishing between these two cancers. METHODS: p63/P501S dual-color sequential immunohistochemical staining was performed on archival material from 132 patients with high-grade UC and 23 patients with PC, and evaluated for p63 (brown nuclear) and P501S (red cytoplasmic) expression. Both the staining intensity and percentage of positive tumor cells were assessed. RESULTS: p63 was positive in 119/132 of UC and negative in PC. P501S was positive in 22/23 of PC and negative in UC. The p63+/P501S- immunoprofile had 90% sensitivity and 100% specificity for UC. The p63-/P501S+ immunoprofile had 96% sensitivity and 100% specificity for PC. CONCLUSION: Our results indicate that double sequential immunohistochemical staining with p63 and P501S is highly specific and can be a useful tool in distinguishing UC from PC especially when there is limited diagnostic tissue as it can be performed on a single slide.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma/diagnóstico , Inmunohistoquímica , Proteínas de la Membrana/análisis , Neoplasias de la Próstata/diagnóstico , Factores de Transcripción/análisis , Proteínas Supresoras de Tumor/análisis , Neoplasias Urológicas/diagnóstico , Carcinoma/química , Carcinoma/patología , Diagnóstico Diferencial , Humanos , Masculino , Clasificación del Tumor , Pennsylvania , Valor Predictivo de las Pruebas , Neoplasias de la Próstata/química , Neoplasias de la Próstata/patología , Sensibilidad y Especificidad , Neoplasias Urológicas/química , Neoplasias Urológicas/patología , Urotelio/química , Urotelio/patología
17.
Int J Immunopathol Pharmacol ; 24(2): 489-97, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21658323

RESUMEN

Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of this study is to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP, the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being -5% in non-recurrent PUNLMP, -15% in recurrent PUNLMP and -24% in UC. Concerning methylation, there is a slight increase in non-recurrent PUNLMP (+5%), a decrease in recurrent PUNLMP (-19%) followed by a sharp rise for the UC (+61%). In conclusion, there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.


Asunto(s)
5-Metilcitosina/análisis , Carcinoma Papilar/química , Metilación de ADN , Histonas/análisis , Recurrencia Local de Neoplasia , Procesamiento Proteico-Postraduccional , Neoplasias Urológicas/química , Acetilación , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Carcinoma Papilar/terapia , Diagnóstico Diferencial , Estudios de Factibilidad , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Lisina , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias Urológicas/genética , Neoplasias Urológicas/patología , Neoplasias Urológicas/terapia , Urotelio/química , Urotelio/patología
18.
Eur Urol ; 60(2): 344-9, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21645967

RESUMEN

BACKGROUND: Sunitinib has activity in patients with metastatic urothelial cancer (UC), but most patients do not respond. OBJECTIVE: To identify predictors of response to sunitinib. DESIGN, SETTING, AND PARTICIPANTS: Seventy-seven patients with advanced UC received sunitinib on one of two schedules at a single institution. Blood pressure (BP), immunohistochemistry (IHC), and pharmacokinetic (PK) results were correlated with response to sunitinib. MEASUREMENTS: BP was assessed on day 1 and 28 of each cycle and on day 14 of cycle 1. IHC was performed on 55 samples from 38 cases using mammalian target of rapamycin and hypoxia-inducible factor (HIF) pathway marker antibodies. Blood samples for PK analysis were collected from 15 patients at three time points. Response was assessed using Response Evaluation Criteria in Solid Tumors criteria. RESULTS AND LIMITATIONS: Sunitinib-induced hypertension predicted improved response when hypertension was categorized as a discrete (p = 0.02) or continuous variable (p = 0.005 [systolic BP] and p = 0.007 [diastolic BP]). The odds ratio of response was 12.5 (95% confidence interval, 1.95-246.8) for grade 3/4 hypertension compared with grade 0. Response was associated with low HIF-1α expression in primary (p = 0.07) tissue. A nonstatistically significant trend was seen for an association between greater drug concentration and best response. A correlation between expression markers within the same pathways was identified, phosphorylated-4EBP1 and phosphorylated-S6 (p = 6.5 × 10(-9)), and vascular endothelial growth factor receptor 2 and HIF-1α (p = 0.008). Results are limited by small numbers. CONCLUSIONS: Clinical and molecular biomarkers of response to sunitinib may have clinical relevance and require prospective validation. There is an urgent need for predictive biomarkers to guide the management of UC.


Asunto(s)
Inhibidores de la Angiogénesis/farmacocinética , Biomarcadores de Tumor/antagonistas & inhibidores , Carcinoma de Células Transicionales/tratamiento farmacológico , Inmunohistoquímica , Indoles/farmacocinética , Pirroles/farmacocinética , Neoplasias Urológicas/tratamiento farmacológico , Urotelio/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/análisis , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Biomarcadores de Tumor/análisis , Presión Sanguínea/efectos de los fármacos , Carcinoma de Células Transicionales/química , Carcinoma de Células Transicionales/patología , Proteínas de Ciclo Celular , Esquema de Medicación , Humanos , Hipertensión/inducido químicamente , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Indoles/administración & dosificación , Indoles/efectos adversos , Modelos Logísticos , Ciudad de Nueva York , Fosfoproteínas/análisis , Fosforilación , Pirroles/administración & dosificación , Pirroles/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sunitinib , Serina-Treonina Quinasas TOR/análisis , Análisis de Matrices Tisulares , Resultado del Tratamiento , Neoplasias Urológicas/química , Neoplasias Urológicas/patología , Urotelio/química , Urotelio/patología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisis
19.
Anticancer Res ; 30(6): 2439-45, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20651405

RESUMEN

AIM: To assess HER-2 and p-AKT expression in upper urinary tract urothelial carcinoma (UTUC) in order to determine their value as prognostic factors of tumour progression and cancer-specific survival. PATIENTS AND METHODS: One hundred consecutive UTUC patients were retrospectively included, between 1990-2004, in 4 tissue microarrays for immunostaining. Median follow-up: 33.03 months. RESULTS: Positive HER-2 expression was found in 10 cases and cytoplasmic p-AKT expression in 84 cases; the expression intensity was strong: 30 cases, moderate: 28 and weak: 26. Nuclear p-AKT expression was found in 6 patients: 1 with strong, and 5 with moderate intensity. Nuclear p-AKT expression was an independent factor for tumour progression (HR=4.145, p=0.013), together with grade (HR=4.557, p=0.009) and stage (HR=2.085, p=0.003). In cancer-specific survival analysis, nuclear p-AKT expression (HR=4.268, p=0.017), together with grade (HR=5.214, p=0.035) and stage (HR=2.666, p=0.002) were identified as independent prognostic factors. CONCLUSION: Nuclear p-AKT expression together with stage and grade constitute independent prognostic factors for tumour progression and cancer-specific survival.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt/análisis , Receptor ErbB-2/análisis , Neoplasias Urológicas/química , Urotelio/patología , Anciano , Anciano de 80 o más Años , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Fosforilación , Pronóstico , Proteínas Proto-Oncogénicas c-akt/fisiología , Receptor ErbB-2/fisiología , Estudios Retrospectivos , Transducción de Señal , Análisis de Matrices Tisulares , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patología
20.
Nutr Cancer ; 61(5): 629-33, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19838936

RESUMEN

The aim of this study was to determine serum levels of selenium (Se) in patients with larynx and urinary system cancers. We also estimated the influence of dietary habits on Se status in examined patients. The mean content of Se in serum of patients with urinary system cancer (48.94 +/- 16.3 mu/l) and larynx cancer (51.00 +/- 18.6 mu/l) was lower than the mean content of Se in the control group (68.25 +/- 15.6 mircog/l; P = 0.000006 or 64.03 +/- 16.8 microg/l; P = 0.0112, respectively). In tissue only, the mean level of Se in patients with kidney cancer (75.37 +/- 40.3 mircog/l) was lower to compare with the dead body control group (220.68 +/- 83.6 microg/l). We have observed the correlation between the content of Se in serum and tissue (r = 0.297; P = 0.002). Patients with studied cancers have deficiency of Se in serum and kidney tissue, and it depends on the diet in about 30%. Frequent consumption of eggs, ham, and wine has the biggest influence on the content of Se in serum of patients in Poland, whereas frequent consumption of pulses, eggs, bacon, and lard is connected with the content of Se in tissue.


Asunto(s)
Dieta , Conducta Alimentaria , Alimentos , Neoplasias Laríngeas/sangre , Estado Nutricional , Selenio/sangre , Neoplasias Urológicas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Encuestas sobre Dietas , Femenino , Humanos , Neoplasias Laríngeas/química , Masculino , Persona de Mediana Edad , Polonia , Análisis de Regresión , Factores de Riesgo , Selenio/análisis , Selenio/deficiencia , Neoplasias Urológicas/química
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