RESUMO
BACKGROUND: Nephroblastoma or Wilms tumor is the most frequent kidney cancer in children and accounts for 98% of kidney tumors in this age group. Despite favorable prognosis, a subgroup of these patients progresses to recurrence and death. The retinoic acid (RA) pathway plays a role in the chemoprevention and treatment of tumors due to its effects on cell differentiation and its antiproliferative, anti-oxidant, and pro-apoptotic activities. Reports describe abnormal cellular retinoic acid-binding protein 2 (CRABP2) expression in neoplasms and its correlation with prognostic factors and clinical and pathological characteristics. The aim of this study was to evaluate the immunohistochemical expression of retinoic acid receptor alpha (RARA) and CRABP2 in paraffin-embedded samples of nephroblastomas via semiquantitative and quantitative analyses and to correlate this expression with prognostic factors. METHODS: Seventy-seven cases of nephroblastomas were selected from pediatric oncology services. The respective medical records and surgical specimens were reviewed. Three representative tumor samples and one non-tumor renal tissue sample were selected for the preparation of tissue microarrays (TMA). The Allred scoring system was used for semiquantitative immunohistochemical analyses, whereas a morphometric analysis of the stained area was employed for quantitative evaluation. The nonparametric Mann-Whitney test was used for comparisons between two groups, while the nonparametric Kruskal-Wallis test was used to compare three or more groups. RESULTS: Immunopositivity for RARA and CRABP2 was observed in both the nucleus and cytoplasm. All histological components of the nephroblastoma (blastema, epithelium, and stroma) were positive for both markers. RARA, based on semiquantitative analyses, and CRABP2, bases on quantitative analyses, exhibited increased immunohistochemical expression in patients with metastasis, with p values of 0.0247 and 0.0128, respectively. These findings were similar to the results of the quantitative analysis of RARA expression, showing greater immunopositivity in tumor samples of patients subjected to pre-surgical chemotherapy. No significant correlation was found with the other variables studied, such as disease stage, anaplasia, risk group, histological type, nodal involvement, and clinical evolution. CONCLUSIONS: Semiquantitative and quantitative analyses of the markers RARA and CRABP2 indicate their potential as biomarkers for tumor progression and their participation in nephroblastoma tumorigenesis.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Renais/patologia , Receptores do Ácido Retinoico/biossíntese , Receptor alfa de Ácido Retinoico/biossíntese , Tumor de Wilms/patologia , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
El interés en el estudio de la vitamina A se ha visto incrementado, durante los últimos años, debido al descubrimiento de las múltiples funciones que tiene esta vitamina en la diferenciación celular de tejidos epiteliales, en el crecimiento, en la reproducción y en la visión. Esta revisión describe los avances recientes sobre el metabolismo de la vitamina A y la función de siete proteínas, que fijan retinoides, en el transporte y presentación de los retinoides a sus correspondientes enzimas, para la transforación de los diferentes retinoides en el organismo o en el interior de la célula. Estas proteínas son: proteína que une retinol (RBP); proteína celular que une retinol (CRBP); proteína celular que une retinol tipo dos (CRBP-II); proteína celular que une al ácido retinoico (CRABP); proteína celular que une ácido retinoico tipo dos (CRABO-II); proteína celular que une retinal(CRALBP); y proteína que une retinol interfotorreceptor (IRBP). Además, se describe la función y los mecanismos de regulación de la expresión de genes por el ácido retinoico
Assuntos
Fígado/metabolismo , Receptores do Ácido Retinoico/biossíntese , Receptores do Ácido Retinoico/química , Proteínas de Ligação ao Retinol/biossíntese , Proteínas de Ligação ao Retinol/fisiologia , Tretinoína , Vitamina A/biossíntese , Vitamina A/química , Vitamina A/fisiologiaRESUMO
Retinoic acid (RA) inhibits 3T3 adipogenesis in a dose-dependent and reversible manner, but its mechanism of action remains unknown. 3T3-F442A cell variants obtained by mutagenesis with nitrosoguanidine and/or selection with high RA concentrations showed different resistance to RA cytotoxicity and underwent adipose conversion of various extents when they were cultured in adipogenic conditions. Commitment to adipose differentiation was also inhibited by RA in these clones. Gel filtration chromatography showed the presence of a cytosolic RA-binding activity in the parental cells but not in three of the variant clones isolated. We demonstrate that cytoplasmic RA-binding activity is not essential for the inhibitory effects of the retinoid on 3T3 adipogenesis, or for resistance to RA cytotoxicity. Other mechanisms should be involved to explain the inhibition of adipose differentiation by RA.