CD163 versus CD68 in tumor associated macrophages of classical hodgkin lymphoma

Classical Hodgkin lymphoma (CHL) is a B-cell lymphoproliferative disorder with a relatively good prognosis. A small but significant percentage of patients, however, will respond poorly to therapy. A recent gene expression profiling study has identified a macrophage signature which has been correlated with primary treatment failure, and immunohistochemical tissue microarray for CD68 was shown to reflect the gene signature as a potentially clinically useful marker to predict adverse prognosis

Efficacy of epidermal growth factor receptor targeting in advanced chordoma: case report and literature review

<p>Abstract</p> <p>Background</p> <p>Chordomas are very rare low-grade malignant bone tumors that arise from the embryonic rests of the notochord. They are characterized by slow growth and long history with frequent local relapses, and sometimes metastases. While chemotherapy is not efficient, imatinib has shown antitumor activity.</p> <p>Case presentation</p> <p>We report on a 76-year-old patient with EGFR-overexpressing advanced chordoma that progressed on imatinib and subsequently responded to erlotinib during 12 months.</p> <p>Conclusions</p> <p>We report the fourth case of advanced chordoma treated with an EGFR inhibitor. We also review the literature concerning the rationale and potential of EGFR targeting in chordoma.</p

The risk and nature of flares in juvenile idiopathic arthritis: Results from the ReACCh-Out cohort

Objective To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis ( JIA) and to identify clinical features associated with an increased risk of flare. Methods We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression. Results 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA \u3e30 mm, maximum active joint count \u3e4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. Conclusions In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare

Rare copy number variants contribute to congenital left-sided heart disease

Left-sided congenital heart disease (CHD) encompasses a spectrum of malformations that range from bicuspid aortic valve to hypoplastic left heart syndrome. It contributes significantly to infant mortality and has serious implications in adult cardiology. Although left-sided CHD is known to be highly heritable, the underlying genetic determinants are largely unidentified. In this study, we sought to determine the impact of structural genomic variation on left-sided CHD and compared multiplex families (464 individuals with 174 affecteds (37.5%) in 59 multiplex families and 8 trios) to 1,582 well-phenotyped controls. 73 unique inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD cohort. After stringent filtering, our gene inventory reveals 25 new candidates for LS-CHD pathogenesis, such as SMC1A, MFAP4, and CTHRC1, and overlaps with several known syndromic loci. Conservative estimation examining the overlap of the prioritized gene content with CNVs present only in affected individuals in our cohort implies a strong effect for unique CNVs in at least 10% of left-sided CHD cases. Enrichment testing of gene content in all identified CNVs showed a significant association with angiogenesis. In this first family-based CNV study of left-sided CHD, we found that both co-segregating and de novo events associate with disease in a complex fashion at structural genomic level. Often viewed as an anatomically circumscript disease, a subset of left-sided CHD may in fact reflect more general genetic perturbations of angiogenesis and/or vascular biology

Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Low-grade extraskeletal osteosarcomas (ESOS) are extremely rare.</p> <p>Case presentation</p> <p>We present the first case of low-grade ESOS of the chest wall, which occurred in a 30-year-old man. Because of initial misdiagnosis and patient's refusal of surgery, the diagnosis was done after a 4-year history of a slowly growing mass in soft tissues, leading to a huge (30-cm diameter) calcified mass locally extended over the left chest wall. Final diagnosis was helped by molecular analysis of <it>MDM2 </it>and <it>CDK4 </it>oncogenes. Unfortunately, at this time, no surgical treatment was possible due to loco-regional extension, and despite chemotherapy, the patient died one year after diagnosis, five years after the first symptoms.</p> <p>Conclusion</p> <p>We describe the clinical, radiological and bio-pathological features of this unique case, and review the literature concerning low-grade ESOS. Our case highlights the diagnostic difficulties for such very rare tumours and the interest of molecular analysis in ambiguous cases.</p

TIA-1 Cytotoxic Granule-Associated RNA Binding Protein Improves the Prognostic Performance of CD8 in Mismatch Repair-Proficient Colorectal Cancer

Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases, has not been performed

Nature and importance of follicular lymphoma precursors

International audienceIt is now widely recognized that cancer development is a protracted process requiring the stepwise acquisition of multiple oncogenic events. In humans, this process can take decades, if not a lifetime, blurring the notion of 'healthy' individuals. Follicular lymphoma exemplifies this multistep pathway of oncogenesis. In recent years, variants of follicular lymphoma have been recognized that appear to represent clonal B-cell expansions at an early stage of follicular lymphoma lymphomagenesis. These include follicular lymphoma in situ, duodenal follicular lymphoma, partial involvement by follicular lymphoma, and in the blood circulating follicular lymphoma-like B cells. Recent genetic studies have identified similarities and differences between the early lesions and overt follicular lymphoma, providing important information for understanding their biological evolution. The data indicate that there is already genomic instability at these early stages, even in instances with a low risk for clinical progression. The overexpression of BCL2 in t(14;18)-positive B cells puts them at risk for subsequent genetic aberrations when they re-enter the germinal center and are exposed to the influences of activation-induced cytidine deaminase and somatic hypermutations. The emerging data provide a rationale for clinical management and, in the future, may identify genetic risk factors that warrant early therapeutic intervention