Detection of 14q32 rearrangements in multiple myeloma, using simultaneous FISH analysis combined with immunofluorescence

14q32 rearrangement has been identified as a recurrent hotspot of translocations in multiple myeloma [MM]. The Fluorescence Immunophenotyping and Interphase Cytogenetics as a tool for the Investigation of Neoplasms [known as FICTION technique] for evaluation of chromosomal changes in MM. The aim of this work is to detect 14q32 rearrangement, using FICTION technique, on archival bone marrow [BM] slides of MM patients, and to study its prognostic value. This study was conducted at Ain Shams University Hospital. The FICTION technique, which uses CD138 and dual color, and the break-apart 14q32 rearrangement probe, was performed on archived smears of BM slides for 50 MM patients at the time of diagnosis. A significantly higher percentage of cases were positive for 14q32 rearrangement by FICTION [32%] compared to fluorescence in situ hybridization [FISH] [12%] [p = 0.04]. Cases positive by FICTION for the rearrangement were designated as Group A, while negative cases were designated as Group B. Significantly lower Hb and CRP levels were found among Group B when compared to Group A patients [p = 0.001 and 0.01, respectively]. Serum albumin level and Bence Jones protein [BJP] significantly affect overall survival [OS] [p = 0.01, 0.007, respectively]. However, a statistically non-significant shorter mean survival time was found in positive cases through FICTION versus negative cases. FICTION technique provides a sensitive tool for establishing clonal plasma cells [PC] infiltration of BM aspirates, and is amenable for use on archived as well as fresh smears

Prognostic value of immunohistochemical classification of diffuse large B-cell lymphoma into germinal center B-cell and non-germinal center B-cell subtypes

To study the expression of germinal center B-cell [GCB]/activated B-cell like-related proteins to get optimal stratification of diffuse large B-cell lymphoma [DLBCL] patients, and correlate this with the established clinical and laboratory parameters. This study was conducted retrospectively on 30 archival paraffin tissue blocks of DLBCL. All patients were diagnosed between April 2004 and January 2007 at Ain Shams University Hospital and National Cancer Institute, Cairo, Egypt. All patients received anthracycline-based regimens, and none of them received rituximab immunotherapy. Each case included in this study was investigated by immunohistochemical reaction for multiple myeloma-1/ interferon regulatory factor-4, B-cell/lymphoma 6, and cluster of differentiation 10 monoclonal antibodies. Patients were classified as GCB group [17 patients] and non-GGB group [13 patients]. We found a statistically significant association between non-GCB phenotype and performance status [PS] >1, high lactate dehydrogenase [LDH] level, advanced international prognostic index [IPI], and poor patient outcome. Non-GCB phenotype, high LDH level, and PS>1 were all associated with increased mortality risk. The median survival time was 46.9 months in group A compared to 19.6 months in group B [hazard ratio [HR]=3.30; 95% confidence interval [CI]=0.52-21.10]. Using multivariate Cox regression analysis, non-GCB phenotype was found to be the most predicting factor [HR=6.07; 95% CI=1.6-22.9; p=0.008]. The subclassification of DLBCL into GCB and non-GCB groups using immunohistochemistry may be useful for identifying those patients whose prognosis is so poor that more aggressive therapy can be given at the time of diagnosis

Tissue factor, tissue factor pathway inhibitor and factor VII activity in cardiovascular complicated type 2 diabetes mellitus

Tissue factor [TF] is the main initiator of the extrinsic coagulation pathway through factor VII [FVII] activation, which is physiologically inhibited by tissue factor pathway inhibitor [TFPI]. Alteration of this pathway has been described in Type 2 diabetes mellitus [T2DM]. The aim of this study is to assess TF and TFPI plasma levels and FVII coagulant activity [FVIIa] in T2DM in relation to cardiothrombotic disease and their correlation to metabolic and clinical behavior of the patients. The study was conducted on 80 T2DM patients divided to accordingly; groupI: 40 patients without a history or clinically detected heart disease, and groupII: 40 patients with a history of myocardial infarction compared to 30 controls. The patients were recruited from Ain Shams University diabetes clinic from September 2007 to February 2009 after informed consent was obtained. Peripheral blood samples were taken for measurement of plasma TF and TFPI levels using ELISA technique and quantitative FVIIa using FVII deficient plasma. Plasma levels of TF, TFPI and FVIIa were significantly higher in T2DM patients compared to the controls [p<0.001]. TF [236.50 +/- 79.23]and TFPI [242.33 +/- 85.84]were significantly higher in group II, compared to group I [150.33 +/- 81.16], [152.8 +/- 82.46], [p<0.001]. TF and TFPI were significantly correlated to body mass index and glycemic control. Also, TF and TFPI were significantly higher in hypertensives [p=0.001] and dyslipidemics [p=0.006] but not in smokers [p=0.64], [p=0.11] respectively. There was a correlation between high TF, TFPI plasma levels, FVIIa activity and cardiothrombotic complications in T2DM especially in the presence of high risk factors such as poor glycemic control, dyslipidemia and obesity. Future target therapy against TF may be beneficial for T2DM patients