| Objective:(1) To investigate the immunohistochemical profiles and their prognostic role in patients with diffuse large B-cell lymphoma (DLBCL).(2) To study the genetic abnormalities about BCL-6、MYC gene rearrangement and p53deletion in DLBCL and analyze their correlations with immunosubtype and prognosis.(3) To explore the significance of miR-155, miR-34a and miR-30a expression in DLBCL.Methods:46cases of DLBCL diagnosed according to the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues (2008) were collected from the First People’s Hospital of Changzhou. Immunohistochemistry(Envision method) was used to evaluate the expression of CD3、CD10、CD20、BCL-6、BCL-2、MUM1and Ki-67in DLBCL. The DLBCLs were classified into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subtypes according to Hans’ algorithm. Interphase fluorescence in situ hybridization (I-FISH) was performed to detect the BCL-6、 MYC and p53gene status. RNA was extracted from tissues using paraffin block RNA Isolation kit according to the manufacture’s protocol. Three DLBCL related miRNAs: miR-155, miR-34a and miR-30a expression were detected by TaqMan real-time fluorescence quantitative real-time polymerase chain reaction. Expression of miRNA was analyzed with comparative method in Ct value.Results:The percentage of tumor cells expressed CD10, BCL-6, MUM1and BCL-2were21.7%(10/46)、60.9%(28/46)、63.0%(29/46) and54.3%(25/46) respectively.16cases (34.8%) were GCB type and the rest (65.2%) were non-GCB type. The BCL-6positive case had a better clinical outcome than that of the BCL-6negative cases.[overall survival (OS), P=0.010; progression-free survival (PFS), P=0.035], whereas the BCL-2positive case had a worse clinical outcome than that of the BCL-2negative cases (OS, P=0.024; PFS, P=0.046). The GCB subtype had a better clinical outcome than that of non-GCB subtype (OS, P=0.032; PFS, P=0.013). BCL6rearrangement was detected in10of the46cases and the presence of the gene rearrangement showed no correlation with BCL6protein expression (P=0.245). OS and PFS were not influenced by BCL-6gene rearrangements (OS,P=0.138; PFS,P=0.095). ALL of the MYC rearrangement was detected in GCB type. The p53deletion was detected in14of the46cases. It was significantly associated with shorter OS (P=0.046) and PFS (P=0.043). Compared with normal controls, the expression level of miR-155was significantly higher in DLBCL (P=0.011). The expression level of miR-155in non-GCB type was higher than that in GCB type (P=0.000). It was showed that the patients with MYC rearrangement had lower expression level of miR-155than that in the negative group (P=0.024). Compared with p53normal group, the expression level of miR-34a in p53deletion group was significantly lower (P=0.015). It was also showed that the BCL-6protein positive group had lower expression level of miR-30a than that in the negative group (P=0.010).Conclusion:The expression of BCL-2was associated with unfavourable prognosis, whereas BCL-6showed favourable prognosis. The prognosis of GCB subtype of DLBCL is better than that of non-GCB subtype. BCL-6gene rearrangement showed no correlation with BCL6protein expression. MYC gene translocation was more common in GCB type than that in non-GCB type. The DLBCL with p53deletion had a poor prognosis. Moreover, the p53gene may be a useful prognostic indicator in DLBCL. The expression levels of miR-155are different in normal controls, DLBCL and its subtypes. It has a diagnosis value in DLBCL. miR-34a is of great prognostic significance in DLBCL. miR-155, miR-34a and miR-30a may be the potential therapy targets for DLBCL... |
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