RESUMEN
Lysosomal acid lipase deficiency is an autosomal recessive disorder with two distinct clinical phenotypes. Wolman disease is rapidly progressive with onset in early infancy. Complete enzyme deficiency results in massive accumulation of cholesterol esters and triglycerides in intestines, liver, spleen and other monocyte-macrophage system cells causing malabsorption, hepatosplenomegaly, liver failure and death in early infancy. Cholesterol ester storage disease may be diagnosed in childhood or later in life. It is characterized by chronic course and variable progression. Main features are variously expressed hepatopathy, including cirrhosis and liver failure, hypercholesterolemia and premature atherosclerosis. Characteristic is pathohistological finding of microvesicular steatosis and fibrosis and patognomonic are typical cholesterol ester crystals. Diagnosis is confirmed by enzyme assay and/or gene analysis. Until recently treatment was symptomatic. Ongoing clinical trials of enzyme replacement therapy have shown very promising results. We are presenting an infant with Wolman disease and two children with cholesterol ester storage disease with the aim to raise awareness about this disease and to start optimal care early.
Asunto(s)
Enfermedad de Acumulación de Colesterol Éster/tratamiento farmacológico , Terapia de Reemplazo Enzimático , Enfermedad de Wolman/tratamiento farmacológico , Niño , Enfermedad de Acumulación de Colesterol Éster/complicaciones , Enfermedad de Acumulación de Colesterol Éster/diagnóstico , Humanos , Lactante , Enfermedad de Wolman/complicaciones , Enfermedad de Wolman/diagnóstico , Enfermedad de WolmanRESUMEN
HER-2/neu extracellular domain (ECD) can be detected in blood as a soluble circulating protein. The aim of this study was to analyze the relationship between HER-2/neu extracellular domain in the serum and the prognosis in breast cancer patients. We also correlated HER-2/neu ECD with various clinicopathological factors including steroid receptor, HER-2/neu receptor coexpression. The serum from seventy nine patients with invasive breast cancer and twenty individuals without malignancy was analyzed using the enzyme-linked immune adsorbent assay method. The cut-off value was estimated by the ROC curve analysis (15.86 µg/L). HER-2/neu ECD values in the serum of patients with breast cancer were significantly higher than in control subjects. Circulating HER-2/neu ECD was significantly associated with the histological grade of tumors and the status of axillary lymph nodes. Negative correlation was observed between HER-2/neu ECD in the serum and estrogen receptor positivity. When we analyzed HER-2/neu ECD in relation with coexpression of steroid receptor and HER-2/neu receptor in tissue, statistically higher values were found in the subgroup of patients with steroid receptor negative, HER-2/neu negative tumors than in the other subgroups. HER-2/neu ECD was not an independent factor in the univariate and multivariate analysis. However, elevated HER-2/neu ECD levels were found in patients with breast cancer possessing more aggressive phenotype.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Células Neoplásicas Circulantes/metabolismo , Receptor ErbB-2/sangre , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Células Neoplásicas Circulantes/patología , Pronóstico , Tasa de SupervivenciaRESUMEN
In our study we have compared the prognostic value of two distinct methods of immunohistochemical Ki-67 determination, tissue microarray (TMA) and classical whole section analysis. "Cut-off" values were used according to the 2009 St. Gallen Consensus. Tissue specimens were obtained from a consecutive retrospective series of 215 female patients with primary invasive tumours. Two hundred and thirteen patients were included in the study. Data on Ki-67 was collected by both tissue microarray (TMA) and whole section analysis. Follow up data on overall (OS) and disease-free survival (DFS) were collected. Median follow-up was 95 months (range from 7.8 through 107 months). Mutual correlation of two Ki-67 determination methods was non-significant (Person's r = 0.13417; p = 0.0528). There was statistically significant association of whole section Ki-67 expression with histological and nuclear grade, progesterone receptor and HER2/neu status. The expression of Ki-67 protein in TMAs correlated only with histological and nuclear grade, but not with other traditional clinicopathological factors. Statistically significant differences in DFS (p = 0.0156) and OS (p = 0.0028) were confirmed between subgroups with low and high whole section Ki-67 expression. When subgroups with high and intermediate expression were compared, significant difference was found in DFS (p = 0.0272), but not in OS (p = 0.0624). On the other hand, there was no statistically significant difference either in DFS, or in OS, according to the expression of Ki-67 in TMAs (p = 0.6529; p = 0.7883; p = 0.7966 for DFS, and p = 0.8917; p = 0.6448; p = 0.4323 for OS, respectively). In our study, classical whole section was superior to TMA analysis in terms of prognosis and clinicopathological correlation. Our results indicate that the method used may have impact on prognostic significance of Ki-67. Further studies are needed, covering a greater number of patients and including a precisely defined stage and treatment patient cohorts, in order to solve controversies in Ki-67 assessment methodology.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Inmunohistoquímica/métodos , Antígeno Ki-67/metabolismo , Análisis de Matrices Tisulares/métodos , Biomarcadores de Tumor/genética , Neoplasias de la Mama/metabolismo , Proliferación Celular , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Antígeno Ki-67/genética , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Significant advances in early breast cancer detection and increased quality of care within developed countries resulted in longer than five years survival in almost 90% of women diagnosed and treated for breast cancer. One in twenty women diagnosed with breast cancer will develop a new primary non-breast malignancy within 10 years from initial diagnosis. Mutations in BRCA 1 i 2, RAD51C, MMR, p53, CDKN2A and 113insArg genes are linked with increased risk of breast cancer and other cancer sites. It seems that treatment modalities also play significant role in development of new primary malignancies. Tissues that receive higher doses of radiation during radiotherapy of breast cancer are under increased risk of developing new primary tumor, especially in younger women, ten years after the treatment. Chemotherapy may cause higher incidence of leukemia and myelodysplastic syndrome but lower overall risk for development of other malignancies. Connection between tamoxifen therapy and increased risk of endometrial cancer is well known and confirmed also in recent studies. The true mechanism of cancer development is still unclear. Significance of hereditary factors, possible common environmental risk factors or unwanted side effects of the specific anticancer treatments are yet to be discovered.