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| 2. |
- Ehinger, Mats, et al.
(författare)
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A Subset of CD5- Diffuse Large B-Cell Lymphomas Expresses Nuclear Cyclin D1 With Aberrations at the CCND1 Locus.
- 2008
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Ingår i: American Journal of Clinical Pathology. - 1943-7722 .- 0002-9173. ; 129:4, s. 630-638
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Tidskriftsartikel (refereegranskat)abstract
- In 231 diffuse large B-cell lymphomas, the expression of cyclin D1 and CD5 was evaluated. All cases were CD5-. Ten (4.3%) were positive for cyclin D1 and were subjected to fluorescence in situ hybridization at the CCND1 locus. One case showed the t(11;14). In another case, the telomeric probe signal for cyclin D1 was lost in most tumor cells, and in a small proportion of the cells, there were fluorescence signals indicative of the t(11;14). Two other cases displayed additional cyclin D1 signals in the absence of the t(11;14). All cases but 1 were positive for bcl-6 or MUM1, disfavoring the possibility of misdiagnosed blastoid variants of CD5- mantle cell lymphomas. Thus, contrary to the current view, there seems to exist a certain number of cyclin D1+ and CD5- diffuse large B-cell lymphomas, some of which have structural aberrations at the CCND1 locus, including the t(11;14).
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| 3. |
- Fjordén, Karin, et al.
(författare)
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Gene expression profiling indicates that immunohistochemical expression of CD40 is a marker of an inflammatory reaction in the tumor stroma of diffuse large B-cell lymphoma
- 2012
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 53:9, s. 1764-1768
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Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemical expression of CD40 is seen in 60-70% of diffuse large B-cell lymphoma (DLBCL) and is associated with a superior prognosis. By using gene expression profiling we aimed to further explore the underlying mechanisms for this effect. Ninety-eight immunohistochemically defined CD40 positive or negative DLBCL tumors, 63 and 35 respectively, were examined using spotted 55K oligonucleotide arrays. CD40 expressing tumors were characterized by up-regulated expression of genes encoding proteins involved in cell-matrix interactions: collagens, integrin a V, proteoglycans and proteolytic enzymes, and antigen presentation. Immunohistochemistry confirmed that CD40 positive tumors co-express the proinflammatory proteoglycan biglycan (p = 0.005), which in turn correlates with the amount of infiltrating macrophages and CD4 and CD8 positive T-cells. We postulate that immunohistochemical expression of CD40 mainly reflects the inflammatory status in tumors. A high intratumoral inflammatory reaction may correlate with an increased autologous tumor response, and thereby a better prognosis.
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| 4. |
- Linderoth, Johan, et al.
(författare)
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CD40 expression identifies a prognostically favourable subgroup of diffuse large B-cell lymphoma
- 2007
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 48:9, s. 1774-1779
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Tidskriftsartikel (refereegranskat)abstract
- In order to confirm our earlier findings of the prognostic effects of CD23 and CD40 expression in diffuse large B-cell lymphoma (DLBCL), possibly due to association with the germinal center (GC) phenotype and/or an increased autologous tumour response, tumour specimens from 125 patients with de novo DLBCL were investigated for immunohistochemical expression of CD23, CD40, BCL6, CD10, MUM1, CD4 and CD8. CD40 was positive in 64% and was associated with improved overall survival (p = 0.03). A GC phenotype was present in 47%, and was also associated with a better overall survival (p = 0.006) but did not correlate with CD40-expression. There was no correlation between amount of tumour infiltrating T-cells and CD40-positivity. CD23 was positive in 10% and expression did not correlate with prognosis. In conclusion, the prognostic effect of CD40 expression was confirmed, but did not correlate with GC-phenotype or T-cell infiltration.
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| 5. |
- Linderoth, Johan, et al.
(författare)
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Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma
- 2008
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 141:4, s. 423-32
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Tidskriftsartikel (refereegranskat)abstract
- In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.
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| 7. |
- Linderoth, Johan, et al.
(författare)
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Tissue microarray is inappropriate for analysis of BCL6 expression in diffuse large B-cell lymphoma
- 2007
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 79:2, s. 146-149
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In this study, our aim was to investigate how different immunohistochemical techniques may influence the result of BCL6 positivity and categorization in germinal center (GC) and non-GC derived diffuse large B-cell lymphoma (DLBCL), as it has been proposed that classification of DLBCL according to cell-of-origin by immunohistochemistry may be performed as a routine procedure in the diagnostic work-up. However, a number of technical issues need to be solved before introducing this as a standard technique. Methods: Tumor specimens from 122 patients with de novo stage II–IV disease, adequately treated with anthracycline-containing chemotherapy regimens were collected. Immunohistochemical expression of BCL6, CD10, and MUM-1/IRF4 was examined using a tissue microarray (TMA) technique. BCL6 and CD10 were also evaluated on whole tissue sections. Results: Due to profound tissue heterogeneity, BCL6 showed a wide range of positivity, with a high number of false negative results by TMA (25% positive), compared to 53% on whole tissue sections (WTS). CD10 was more homogeneously expressed, and TMA results corresponded better to WTS. Consequently, the results from categorization into GC and non-GC DLBCL differed considerably by use of the two methods, and resulted in very different outcome in terms of overall survival. Conclusion: Immunohistochemical GC-status determined on TMA is not reliable enough to be used for individual treatment decisions in DLBCL, mostly due to difficulties in interpreting BCL6 status.
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