Detection of free immunoglobulin light chains in cerebrospinal fluids of patients with central nervous system lymphomas.
ABSTRACT Diagnosis of central nervous system (CNS) lymphoma depends on histopathology of brain biopsies, because no reliable disease marker in the cerebrospinal fluid (CSF) has been identified yet. B-cell lymphomas such as CNS lymphomas are clonally restricted and express either kappa or lambda immunoglobulin light chains. The aim of this study was to find out a potential diagnostic value of free immunoglobulin light chains released into the CSF of CNS lymphoma patients. Kappa (kappa) and lambda (lambda) free immunoglobulin light chains (FLC) were measured in CSF and serum samples collected from 21 patients with primary and secondary CNS lymphomas and 14 control patients with different neurologic disorders. FLC concentrations and ratios were compared between patient groups and were further analyzed in correlation with clinical, cytopathological, and radiological findings. FLC concentrations for all patients were lower in CSF when compared to serum. In patients with CNS lymphoma, the FLC ratios in CSF were higher (range 392-0.3) compared to control patients (range 3.0-0.3). Irrespective of cytopathological proven lymphomatous meningitis, in 11/21 lymphoma CSF samples the FLC ratios were markedly above 3.0 indicating a clonally restricted B-cell population. Increased FLC ratios in CSF were found in those patients showing subependymal lymphoma contact as detected in magnetic resonance imaging. In summary, this is the first report demonstrating that a significant proportion of patients with CNS lymphomas display a markedly increased FLC ratio in the CSF.
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ABSTRACT: Recent studies have provided new insights into the diagnostic value of circulating microRNAs (miRNAs) for hematologic cancers. However, inconsistent results have been reported on the diagnostic performance of various kinds of miRNAs. To systematically assess the potential diagnostic value of miRNAs in hematologic cancers, we conducted the present meta-analysis. Multiple databases (PubMed, Cochrane Library, EMBASE, CNKI, and Wan Fang) were carefully searched for available studies up to April 4, 2014. Sensitivity and specificity were pooled using a random-effects model. Likelihood ratio (LR), diagnostic odds ratio (DOR), and the area under the curve (AUC) were used to measure the diagnostic values. Subgroup and meta-regression analyses were used to find potential sources of heterogeneity. Thirty-four studies from 14 publications, which involved 1,159 hematologic cancer patients and 826 healthy controls, were included in this meta-analysis. The pooled estimates indicated a moderately high diagnostic accuracy for circulating miRNAs, with a sensitivity of 0.83, a specificity of 0.85, a PLR of 5.7, a NLR of 0.20, a DOR of 29, and an AUC of 0.91. The subgroup analyses showed that diagnostic accuracy was better for acute myeloid leukemia (AML) patients and Asians compared with other subgroups. In addition, multiple miRNA assays displayed a better performance than single ones. Furthermore, we found that plasma might be a more promising matrix for detecting the expression of miRNAs than serum. Our results identified the potential use of circulating miRNAs in second-line diagnosis for hematologic cancers, especially the value of miRNA panels. However, further large cohort studies are still required to confirm our findings.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 07/2014;
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ABSTRACT: Recent studies have shown abnormal microRNA (miRNA) expression levels in the central nervous system (CNS) of cancer patients, suggesting that miRNAs may serve as promising biomarkers for cancers of CNS. However, other studies have arrived at conflicting results. Therefore, this meta-analysis aims to systematically measure the potential diagnostic value of miRNAs for CNS cancers. Electronic databases as well as other sources were searched until to April 12, 2014 for relevant articles. Data from different studies were pooled using the random-effects model. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), together with the summary receiver operator characteristic (SROC) curve, and area under the SROC curve (AUC) value were used to estimate overall diagnostic performance. Twenty-three studies from 6 articles were included in the current meta-analysis with a total of 299 CNS cancer patients and 418 controls. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.85 (95 % CI, 0.80-0.89), 0.83 (95 % CI, 0.76-0.88), 5.1 (95 % CI, 3.4-7.5), 0.18 (95 % CI, 0.12-0.26), 28 (95 % CI, 14-58), and 0.91 (95 % CI, 0.88-0.93), respectively. Subgroup analyses showed that cerebrospinal fluid (CSF)-based miRNAs assays yielded more accurate results and seemed to be more sensitive in diagnosing of primary central nervous system lymphoma (PCNSL). In conclusion, miRNAs may be suitable for serving as noninvasive biomarkers for CNS cancers detection. However, further validation based on a larger sample of patients and controls is still required.Molecular neurobiology. 08/2014;
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ABSTRACT: Recently, diffuse-large-B-cell lymphoma (DLBCL) associated with serum IgM monoclonal component (MC) has been shown to be a very poor prognostic subset although, detailed pathological and molecular data are still lacking. In the present study, the clinicopathological features and survival of IgM-secreting DLBCL were analyzed and compared to non-secreting cases in a series of 151 conventional DLBCL treated with R-CHOP. IgM MC was detected in 19 (12.5%) out of 151 patients at disease onset. In 17 of these cases secretion was likely due to the neoplastic clone, as suggested by the expression of heavy chain IgM protein in the cytoplasm of tumor cells. In IgM-secreting cases immunoblastic features (p<.0001), non-GCB-type (p = .002) stage III-IV(p = .003), ≥2 extra nodal sites (p<.0001), bone-marrow (p = .002), central-nervous-system (CNS) involvement at disease onset or relapse (p<.0001), IPI-score 3-5 (p = .009) and failure to achieve complete remission (p = .005), were significantly more frequent. FISH analyses for BCL2, BCL6 and MYC gene rearrangements detected only two cases harboring BCL2 gene translocation and in one case a concomitant BCL6 gene translocation was also observed. None of the IgM-secreting DLBCL was found to have L265P mutation of MYD88 gene. Thirty-six month event-free (11.8% vs 66.4% p<.0001), progression-free (23.5% vs 75.7%, p<.0001) and overall (47.1% vs 74.8%, p<.0001) survivals were significantly worse in the IgM-secreting group. In multivariate analysis IgM-secreting (p = .005, expB = 0.339, CI = 0.160-0.716) and IPI-score 3-5 (p = .010, expB = 0.274, CI = 0.102-0.737) were the only significant factors for progression-free-survival. Notably, four relapsed patients, who were treated with salvage immmunochemotherapy combined with bortezomib or lenalidomide, achieved lasting remission. Our data suggests that IgM-secreting cases are a distinct subset of DLBCL, originating from activated-B-cells with terminally differentiated features, prevalent extra nodal dissemination and at high risk of CNS involvement.PLoS ONE 01/2014; 9(4):e93903. · 3.53 Impact Factor