Mammaglobin B is an independent prognostic marker in epithelial ovarian cancer and its expression is associated with reduced risk of disease recurrence

<p>Abstract</p> <p>Background</p> <p>Traditional prognostic factors in epithelial ovarian cancer (EOC) are inadequate in predicting recurrence and long-term prognosis, but genome-wide cancer research has recently provided multiple potentially useful biomarkers. The gene codifying for Mammaglobin B (MGB-2) has been selected from our previous microarray analysis performed on 19 serous papillary epithelial ovarian cancers and its expression has been further investigated on multiple histological subtypes, both at mRNA and protein level. Since, to date, there is no information available on the prognostic significance of MGB-2 expression in cancer, the aim of this study was to determine its prognostic potential on survival in a large cohort of well-characterized EOC patients.</p> <p>Methods</p> <p>MGB-2 expression was evaluated by quantitative real time-PCR in fresh-frozen tissue biopsies and was validated by immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples derived from a total of 106 EOC patients and 27 controls. MGB-2 expression was then associated with the clinicopathologic features of the tumors and was correlated with clinical outcome.</p> <p>Results</p> <p>MGB-2 expression was found significantly elevated in EOC compared to normal ovarian controls, both at mRNA and protein level. A good correlation was detected between MGB-2 expression data obtained by the two different techniques. MGB-2 expressing tumors were significantly associated with several clinicopathologic characteristics defining a less aggressive tumor behavior. Univariate survival analysis revealed a decreased risk for cancer-related death, recurrence and disease progression in MGB-2-expressing patients (p < 0.05). Moreover, multivariate analysis indicated that high expression levels of MGB-2 transcript (HR = 0.25, 95%, 0.08–0.75, p = 0.014) as well as positive immunostaining for the protein (HR = 0.41, 95%CI, 0.17–0.99, p = 0.048) had an independent prognostic value for disease-free survival.</p> <p>Conclusion</p> <p>This is the first report documenting that MGB-2 expression characterizes less aggressive forms of EOC and is correlated with a favorable outcome. These findings suggest that the determination of MGB-2, especially at molecular level, in EOC tissue obtained after primary surgery can provide additional prognostic information about the risk of recurrence.</p

Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer

BACKGROUND: The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. METHODS: In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription – polymerase chain reaction (RT-PCR). RESULTS: Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. CONCLUSION: The design of new approaches to identify such markers is warranted

Refined diagnostic criteria for bone marrow mastocytosis: a proposal of the European competence network on mastocytosis

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level 65125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL

Refined diagnostic criteria for bone marrow mastocytosis: a proposal of the European competence network on mastocytosis

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p &lt; 0.05) and better overall survival (p &lt; 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels &lt;125 ng/mL

PET and SPECT Imaging in Dystonia

Dystonia is a syndrome characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures. It is a common movement disorder with different forms that can be classified based on different clinical characteristics. Idiopathic focal dystonia (dystonia in one body part with no known cause) is the most common form. The more generalized (throughout the body) forms of dystonia have a younger age of onset and usually an underlying genetic defect. The mode of inheritance is usually autosomal dominant. Of these, the most common are DYT-TOR1A and DYT-THAP1 dystonia. In combined dystonia syndromes, also autosomal dominantly inherited disorders, dystonia patients have additional neurological symptoms (e.g., parkinsonism or myoclonus). This group includes dopamine-responsive dystonia, myoclonus-dystonia, rapid-onset dystonia-parkinsonism, and paroxysmal dystonia. In this chapter, we describe results from positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies in the different forms of dystonia. Three different kinds of PET and SPECT techniques have been used in patients with dystonia: glucose metabolism scans, regional cerebral blood flow studies, and receptor imaging. Increased glucose metabolism was found in the basal ganglia, thalamus, and cerebellum of patients with different forms of focal dystonia and in DYT1 dystonia. Patients with DYT6 dystonia showed decreased glucose metabolism in the putamen. Results from regional cerebral blood flow (rCBF)-activation studies differed extensively among different studies and different patient groups, mainly because of study design. Overall, the primary and secondary motor and sensory cortices were found to be abnormal in almost all forms of dystonia, although the direction of the abnormalities differed. Dopamine was found to play a role in dystonia reflected by decreased dopamine D2/3 receptor binding in the striatum of patients with almost all forms of dystonia. In recent years, it has been established that other neurotransmitter systems, such as serotonin and gamma aminobutyric acid (GABA) also play a role in dystonia. In conclusion, dystonia is likely to be a network disorder with abnormalities in a large number of cortical and subcortical areas. There might be a central role for the basal ganglia with abnormalities in dopamine receptor binding, as well as other neurotransmitter systems