US Shear-Wave Elastography Dispersion for Characterization of Chronic Liver Disease.

Background Little is known about the benefits of the use of dispersion slope (DS) as a viscosity-related parameter derived from two-dimensional (2D) shear-wave elastography (SWE) in the stratification of hepatic pathologic stages. Purpose To evaluate whether DS as an additional parameter can improve the diagnostic performance in detecting liver necroinflammation, fibrosis, and steatosis. Materials and Methods In this prospective study, consecutive participants with chronic liver disease who underwent liver biopsy and 2D SWE were recruited between July 2019 and September 2020. DS and liver stiffness (LS) measurements were obtained with use of a 2D SWE system immediately before biopsy. The biopsy specimens were assessed to obtain the scores of fibrosis, necroinflammation, and steatosis. Differences in the area under the receiver operating characteristic curve (AUC) were used to compare the diagnostic performance of DS, LS, and a combination of DS and LS. Results There were 159 participants evaluated (among them, 79 participants with chronic hepatitis B and 11 participants with nonalcoholic fatty liver disease). The distributions of DS values among various necroinflammatory activities (P = .02) and fibrosis stages (P < .001) were different. Moreover, DS was only associated with fibrosis after subgroup analysis based on the fibrosis stages and necroinflammatory activities (P < .001). The AUCs of DS in detecting clinically significant fibrosis (fibrosis stage ≥F2), cirrhosis (fibrosis stage of F4), and moderate to severe necroinflammatory activity (necroinflammatory activity ≥A2) were 0.72 (95% CI: 0.64, 0.79), 0.71 (95% CI: 0.63, 0.78), and 0.64 (95% CI: 0.55, 0.71), respectively. The differences of AUCs were not apparent for the DS and LS combination model after excluding DS (fibrosis stage ≥F2: 0.00 [95% CI: 0.00, 0.01], fibrosis stage of F4: -0.01 [95% CI: -0.02, 0.00], and necroinflammatory activity ≥A2: 0.00 [95% CI: 0.00, 0.01]). Conclusion The addition of dispersion slope derived from two-dimensional shear-wave elastography did not improve the diagnostic performance in detecting liver fibrosis, necroinflammation, or steatosis in patients with primarily viral hepatitis. ClinicalTrials.gov registration no.: NCT03777293 © RSNA, 2022 Online supplemental material is available for this article.

Shear-Wave Dispersion Slope of the Liver: Effect of Study Protocol and Ascites on the Measurement Applicability.

This study aimed to evaluate the shear-wave dispersion (SWD) scanning protocol including the minimum number of measurements and better size of the region of interest (ROI), as well as the influence of ascites on the measurement applicability. Patients who had undergone serial SWD examinations between July 2019 and December 2020 were included. In patients with chronic liver disease (group A), two different ROI sizes were applied, and at least 10 measurements were repeated to determine the minimum number of measurements and better ROI size. In patients with liver failure (group B), failure and unreliable results were compared between patients with and without ascites. A minimum of five measurements when using a 20-mm ROI and six measurements when using a 10-mm ROI were required. Compared with using a 20-mm ROI, a 10-mm ROI showed a higher unreliable rate. The failure and unreliable rates of SWD in patients with ascites were significantly higher than those in patients without ascites. SWD examination required at least five measurements when using a 20-mm ROI and six measurements when using a 10-mm ROI. A larger ROI was associated with higher reliability, and ascites influenced the failure and reliability of the SWD measurement.

Blastic plasmacytoid dendritic cell neoplasm with skin and bone marrow involvement: Report of three cases.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematopoietic malignancy. BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features with various cutaneous lymphatic hematopoietic tumors. CASE SUMMARY: We report on three BPDCN cases, all characterized by skin nodules and examined by histology, immunohistochemical detection, in situ hybridization for Epstein-Barr virus, and follow-up. We also review the relevant literature. All patients were positive for CD56 and negative for Epstein-Barr encoded small RNA. Two patients had bone marrow involvement. Chemotherapy is the main treatment for BPDCN, but case 1 showed bone marrow suppression and case 2 developed recurrence after chemotherapy. Case 1 survived for 7 mo, case 2 for 17 mo, and case 3 for 9 mo. CONCLUSION: An accurate pathological diagnosis is a precondition for treatment, and the diagnosis of BPDCN should be based on a combination of clinical symptoms, pathological characteristics, immunophenotype, and other auxiliary examinations. It is necessary to clarify the clinicopathological features and biological behavior of BPDCN to improve its understanding by both clinicians and pathologists. Case 2 survived significantly longer than the other two cases, suggesting that the treatment received by case 2 was more effective.

Dynamic Contrast-Enhanced Ultrasound Radiomics for Hepatocellular Carcinoma Recurrence Prediction After Thermal Ablation.

PURPOSE: To develop a radiomics model based on dynamic contrast-enhanced ultrasound (CEUS) to predict early and late recurrence in patients with a single HCC lesion ≤ 5 cm in diameter after thermal ablation. PROCEDURES: We enrolled patients who underwent thermal ablation for HCC in our hospital from April 2004 to April 2017. Radiomics based on two branch convolution recurrent network was utilized to analyze preoperative dynamic CEUS image of HCC lesions to establish CEUS model, in comparison to the conventional ultrasound (US), clinical, and combined models. Clinical follow-up of HCC recurrence after ablation were taken as reference standard to evaluate the predicted performance of CEUS model and other models. RESULTS: We finally analyzed 318 patients (training cohort: test cohort = 255:63). The combined model showed better performance for early recurrence than CUES (in training cohort, AUC, 0.89 vs. 0.84, P < 0.001; in test cohort, AUC, 0.84 vs. 0.83, P = 0.272), US (P < 0.001), or clinical model (P < 0.001). For late recurrence prediction, the combined model showed the best performance than the CEUS (C-index, in training cohort, 0.77 vs. 0.76, P = 0.009; in test cohort, 0.77 vs. 0.68, P < 0.001), US (P < 0.001), or clinical model (P < 0.001). CONCLUSIONS: The CEUS model based on dynamic CEUS radiomics performed well in predicting early HCC recurrence after ablation. The combined model combining CEUS, US radiomics, and clinical factors could stratify the high risk of late recurrence.

Clinical-Pathologic Analysis of Breast Cancer With PIK3CA Mutations in Chinese Women.

PURPOSE: Mutations of PIK3CA have recently been shown to play an important role in the pathogenesis and progression of breast neoplasms. The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA mutation in Chinese breast cancer patients and explored their role in tumor phenotypes. METHODS: Mutational analysis of PIK3CA was done in 113 primary breast cancers of Chinese women used Amplification refractory mutation system (ARMS). The relationship of PIK3CA mutations with several clinicopathologic characteristics was analyzed. RESULTS: PIK3CA gene mutation was identified in 43(38.05%) cases and has a more significant difference between exon 9 and 20. HER2 gene amplification was 32.6% in 43 cases of PIK3CA mutation, but 37.1% in 70 cases of non-mutation (χ2 = 0.245, P > 0.05). There was no significant correlation of the age distribution, lymph node status, histological tumor grading, ER and/or PR and P53 between 2 groups (P > 0.05). CONCLUSION: A high frequency of somatic PIK3CA mutation was detected in Chinese breast cancer patients, especially in exon 20. The relationship between PIK3CA gene mutation and clinical pathological features of breast cancer needs to be further studied in a large series of patients. PIK3CA mutations seem to have the potential to be used in target treatment and as an indicator of prognosis.

Efficacy and safety of cooled and uncooled microwave ablation for the treatment of benign thyroid nodules: a systematic review and meta-analysis.

PURPOSE: To evaluate the effectiveness and safety of microwave ablation (MWA), including cooled MWA (cMWA) and uncooled MWA (uMWA), for the treatment of benign thyroid nodules (BTNs). METHODS: The databases of MEDLINE, EMBASE and Cochrane library were searched up to 3 Jun, 2018. In this meta-analysis, data of volume reduction rates (VRRs) at the 3-, 6- and 12-month follow-up, and complications are obtained to evaluate the effectiveness and safety of cMWA and uMWA for the treatment of BTNs. RESULTS: Nine studies involving 1461 patients with 1845 BTNs were included. The pooled VRR at the 3-month follow-up after MWA therapy reached 54.3% (95% CI: 45.3-63.3%, I2 = 97.6%), 73.5% (95% CI: 66.7-80.3%, I2 = 94.9%) at the 6-month follow-up, and 88.6% (95% CI: 84.9-92.4%, I2 = 92.7%) at the 12-month follow-up. The pooled proportions of overall, major and minor complications were 52.4% (95% CI: 29.8-74.9%; I2 = 99.5%), 4.8% (95% CI: 2.7-7.0%; I2 = 55.9%) and 48.3% (95% CI: 31.2-65.4%; I2 = 99.7%). Both cMWA and uMWA achieved similar pooled VRR at the 3-month follow-up (58.4 vs 45.3%, P = 0.07) and pooled proportion of major complications (4.9 vs 5.0%, P = 0.49), while uMWA had higher pooled proportions of overall and minor complications than cMWA (97.8 vs 29.7%, P < 0.01; 97.8 vs 21.0%, P < 0.01), with more patients suffering pain and skin burn after uMWA (100 vs 5.5%, P < 0.01; 47.2 vs 0.2%, P < 0.01). CONCLUSION: MWA is an effective treatment modality for BTNs. When considering the patient's comfort, cMWA would be a more preferable procedure with less complications.

Complications Following Radiofrequency Ablation of Benign Thyroid Nodules: A Systematic Review.

OBJECTIVE: This systematic review examined whether radiofrequency ablation (RFA) is a safe treatment modality for benign thyroid nodules (BTNs). DATA SOURCES: PubMed, Embase, and the Cochrane Library database were searched for articles that (a) targeted human beings and (b) had a study population with BTNs that were confirmed by fine-needle aspiration cytology and/or core needle biopsy. STUDY SELECTION: Thirty-two studies relating to 3409 patients were included in this systematic review. RESULTS: Based on literatures, no deaths were associated with the procedure, serious complications were rare, and RFA appears to be a safe and well-tolerated treatment modality. However, a broad spectrum of complications offers insights into some undesirable complications, such as track needle seeding and Horner syndrome. CONCLUSIONS: RFA appears to be a safe and well-tolerated treatment modality for BTNs. More research is needed to characterize the complications of RFA for thyroid nodules.

Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a malignant proliferation of CD56(+) and cytoCD3(+) lymphocytes with aggressive clinical course, which is prevalent in Asian and South American populations. The molecular pathogenesis of NKTCL has largely remained elusive. We identified somatic gene mutations in 25 people with NKTCL by whole-exome sequencing and confirmed them in an extended validation group of 80 people by targeted sequencing. Recurrent mutations were most frequently located in the RNA helicase gene DDX3X (21/105 subjects, 20.0%), tumor suppressors (TP53 and MGA), JAK-STAT-pathway molecules (STAT3 and STAT5B) and epigenetic modifiers (MLL2, ARID1A, EP300 and ASXL3). As compared to wild-type protein, DDX3X mutants exhibited decreased RNA-unwinding activity, loss of suppressive effects on cell-cycle progression in NK cells and transcriptional activation of NF-κB and MAPK pathways. Clinically, patients with DDX3X mutations presented a poor prognosis. Our work thus contributes to the understanding of the disease mechanism of NKTCL.

Low expression of microRNA-146b-5p and microRNA-320d predicts poor outcome of large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone.

Although diffuse large B-cell lymphoma (DLBCL) encompasses a biologically and clinically diverse set of diseases, increasing evidence has pointed to an important role of microRNAs (miRs) in the pathogenesis of DLBCL. We report here that low expression of miR-146b-5p and miR-320d is associated with poor prognosis of DLBCL patients treated with the standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen and that this is related to the inhibitory effect of these miRs on DLBCL cell proliferation. Analysis of a retrospective cohort of 106 primary nodal DLBCL samples from patients who were treated with CHOP showed that, when the median survival period (40.8 months) was used as the cutoff point, miR-146b-5p and miR-320d were expressed at lower levels in DLBCLs with poor prognosis. Indeed, whereas low expression of miR-146b-5p was correlated with reduced progression-free survival, low expression of miR-320d was associated with decreases in both progression-free survival and overall survival. Moreover, miR-146b-5p and miR-320d were expressed at significantly lower levels in DLBCLs with the MYC t(8;14) translocation. Functional studies demonstrated that overexpression of miR-146b-5p or miR-320d inhibited DLBCL cell proliferation, wheareas knockdown of miR-146b-5p or miR-320d promoted proliferation of DLBCL cells. Taken together, these results suggest that low expression of miR-146b-5p and miR-320d may be predictive of compromised responses of a subset of DLBCL patients to treatment with the CHOP regimen and that restoration of these miRs may be useful to improve the therapeutic efficacy of CHOP.

[Significance of myc gene rearrangement and its correlation with prognosis in diffuse large B cell lymphoma].

OBJECTIVE: To study the relationship between myc gene rearrangement and myc protein expression in diffuse large B cell lymphoma (DLBCL), and their correlation with prognosis. METHODS: One hundred and six cases of DLBCLs with follow-up data were analyzed using interphase fluorescence in situ hybridization (FISH) technique. Immunophenotyping analysis for CD20, CD3, myc, Mum-1, CD10, bcl-6 was also performed using EnVision immunohistochemistry. RESULTS: The percentages of tumor cells expressing myc, Mum-1, CD10 and bcl-6 were 70.8%, 56.6%, 21.7% and 26.4%, respectively. Twenty six cases (24.5%) were of GCB type and the rest (75.5%) were of non-GCB (non germinal center) type. The myc rearrangement was identified in 13 (12.3%) of 106 cases. 13 cases showed to be of non-GCB type. There was no correlation between myc rearrangement and myc protein expression. DLBCLs (n = 13) with myc rearrangement showed significantly poorer overall survival (OS) and progression free survival (PFS), with a median OS and PFS time of 4.7 and 3.2 months, respectively (for OS and PFS, P < 0.001). Multivariate analysis using Cox proportional hazard model confirmed that myc rearrangement, ECOG performance status of 2-4, immunophenotyping subgroup and myc protein were independent factors affecting the prognosis and significantly associated with the survival. However, myc rearrangement was the strongest prognostic factor. CONCLUSIONS: DLBCL with myc gene rearrangement is a subgroup of non-GCB DLBCL with poor outcome. It is an independent and useful factor for prognosis in DLBCL. Expression of myc is influenced by many factors and myc rearrangement may be one of these factors.

[Significance of microRNA-16 and bcl-2 expression in T lymphoblastic lymphoma/leukemia and its relation with prognosis].

OBJECTIVE: To study the expression of miR-16 and bcl-2 in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) and its relationship to prognosis. METHODS: 70 cases of T-LBL/ALL with follow-up data were studied by using immunohistochemical EnVision method for CD1a, CD3, cCD3, CD7, CD10, CD20, CD23, CD34, CD43, CD45RO, CD99, TDT, MPO, bcl-2 and Ki-67. The expression levels of miR-16 were examined by TaqMan real-time polymerase chain reaction (RT-PCR). Thirty cases of reactive lymph node were selected as control. RESULTS: Among the 70 cases of T-LBL/ALL, the percentages of tumor cells expression of TDT, CD99, CD3, CD7, CD10, CD34, CD1a, cCD3, bcl-2, CD45RO and CD43 were 94.3% (66/70), 94.3% (66/70), 68.6% (48/70), 92.9% (65/70), 32.9% (23/70), 24.3% (17/70), 40.0% (28/70), 51.4% (36/70), 34.3% (24/70), 37.1% (26/70), and 48.6% (34/70). Separately, while tumor cells expression of MPO, CD20 and CD23 was all negative. A figure of Ki-67 expression > 80% was found in 24 cases and ≤ 80% in 46 cases. The expression of miR-16 was up-regulated in T-LBL/ALL, and it was 5.07 times of the reactive lymph node(P = 0.001). The high expression group of miR-16 was significantly correlated with longer over survival (P = 0.041). The prognosis of negative bcl-2 group was better than bcl-2 positive one(P = 0.904). The relationship of miR-16 and bcl-2 was significant(P = 0.042,χ(2) = 4.147). Survival multivariate COX proportional hazard regression analysis revealed that the low expression of miR-16 might be a independent poor prognosis factor (P = 0.049). CONCLUSIONS: While the high expression group of miR-16 has longer OS than that in low expression group. The prognosis of bcl-2 negative was better than bcl-2 positive. miR-16 may be a independent prognosis factor. The relationship of miR-16 and bcl-2 might suggested that gene regulation may be influenced by them.

[Expression of microRNA-223 and its clinicopathologic correlation in diffuse large B-cell lymphoma].

OBJECTIVE: To study the expression of miR-223 in diffuse large B cell lymphoma (DLBCL) with correlation of histoloigcal subtypes and clinical prognosis. METHODS: A total of 45 cases of DLBCL were investigated by immunohistochemistry (EnVision method) for CD20, CD3, CD10, bcl-6 and MUM-1. The cases were classified into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subtypes according to Hans' algorithm. Agilent Human miRNA Microarray 16.0 was used to detect the expression of micro-RNAs in paraffin-embedded tissue of 24 cases of DLBCL that had available clinical follow-up. The expression levels of miR-223 were examined by TaqMan real-time reverse transcription polymerase chain reaction (real-time RT-PCR). Fourteen cases of reactive lymph node were selected as control. RESULTS: Among 45 cases of DLBCL, 16 cases (35.6%) were GCB and 29 cases (64.4%) were non-GCB subtypes. The expression levels of miR-223 measured by real-time RT-PCR were 19.8 and 15.8 in GCB and non-GCB subgroups, respectively (P = 0.236). The expression of miR-223 was up-regulated in DLBCL with 17.2 folds of increase over that of the reactive lymph nodes (P = 0.014). The overexpression of miR-223 was significantly correlated with a longer overall survival (P = 0.011). Multivariate Cox proportional hazard regression analysis identified the following independent poor prognostic factors: low expression of miR-223 (RR = 5.445, 95%CI, 1.555 - 19.068, P = 0.008), abnormal level of LDH (RR = 3.974, 95%CI, 1.191 - 13.266, P = 0.025) and IPI ≥ 3 (RR = 4.044, 95%CI, 1.233 - 13.264, P = 0.021). CONCLUSIONS: The expression of miR-223 has no relationship with the immunophenotypes of DLBCL. As a potential prognostic biomarker, overexpression of miR-223 correlates with a longer OS of patients with DLBCL.

No association between the USP7 gene polymorphisms and colorectal cancer in the Chinese Han population.

Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population.

State of chromosome 11q23 in T-ALL/LBL and their relation to prognosis.

The purpose of this study is to investigate the mixed lineage leukemia gene (MLL, located on chromosome 11q23) expression in T acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL) and its relationship to prognosis. Fifty cases of T-ALL/LBL with clinical data were selected from the Shanxi Cancer Hospital in China. The immunohistochemical EnVision method was used for the expression of CD3, CD7, CD10, CD20, CD23, CD43, CD45RO, CD99, terminal deoxynucleotidyl transferase, myeloperoxidase and ki67. Fluorescent in situ hybridization for MLL gene expression was performed on paraffin-embedded tissue. Among the 50 cases of T-ALL/LBL, the percentages of tumor cells expressing terminal deoxynucleotidyl transferase, CD99, CD3, CD7, CD10, CD43, and CD45RO were 92.0%, 96.0%, 72.0%, 92.0%, 34%, 60.0%, and 40.0%, respectively, whereas myeloperoxidase, CD20, and CD23 were all negative. A level of Ki67 expression >80% was found in 18 cases and ≤80% in 32 cases. The period of follow-up ranged from 1 to 108 months. The overall survival rate was 35.8%, with a median survival time of 330 days. Breakage of 11q23 was detected in 8 (16.00%) and amplification in 14 (28.00%) of the 50 cases. The rate of amplification in stage III-IV was higher than that in stage I-II (P<0.05). The prognosis in the 11q23 breakage group was worse than that in the nonbreakage group (P<0.05). The prognosis in the 11q23 amplification group was also worse than that in the nonamplification group (P<0.05). MLL gene rearrangement is a new subgroup concerned with prognosis in T-ALL/LBL. Both breakage and amplification of 11q23 in T-ALL/LBL might play important roles in the development and progression of T-ALL/LBL.

[Significance of microRNA-146b-5p in diffuse large B-cell lymphoma and its relationship with risk assessment].

OBJECTIVE: To study the expression of miR-146b-5p in diffuse large B cell lymphoma (DLBCL), and its relationship with risk assessment. METHODS: 62 cases of nodal DLBCL with follow-up data were collected from Shanxi Cancer Hospital, and were studied by using immunohistochemical EnVision method for CD3, CD10, CD20, Bcl-6 and MUM1. 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. Agilent Human miRNA Microarray 16.0 was used to select the miRNAs on paraffin-embedded tissues of 24 DLBCL cases. A TaqMan real-time polymerase chain reaction (RT-PCR) method was performed on 62 nodal DLBCL cases to validate the expression levels of miR-146b-5p.11 cases with reactive lymph node were elected as control. RESULTS: In 62 cases of DLBCL, 35.5% of cases were GCB and 64.5% non-GCB subtypes, the expression of miR-146b-5p in GCB was 3.2 times as much as non-GCB subtypes (P = 0.006). The expression of miR-146b-5p was up-regulated in DLBCL, and expression level of miR-146b-5p was 5.4 times as much as reactivated lymph node. In 62 cases of DLBCL, 43.5% cases were recurrence-free and 56.5% recurrence. The expression of miR-146b-5p was remarkably up-regulated in recurrence-free group compared with recurrence group (P = 0.004). Moreover, high expression levels of miR-146b-5p in DLBCL were found to be associated with longer relapse-free survival (P = 0.005), but not for overall survival. Multivariate COX proportional hazard regression analysis revealed that low expression of miR-146b-5p (P = 0.004) and IPI ≥ 3(P = 0.011) were independent poor prognostic factors in 62 cases of DLBCL. CONCLUSIONS: The expression of miR-146b-5p was up-regulated in recurrence-free group, and its higher expression levels in DLBCL were associated with improved relapse-free survival. Our results suggested that miR-146b-5p might be one of markers for risk assessment.

Clinical significance and prognosis of MYC translocation in diffuse large B-cell lymphoma.

Recent studies have suggested that chromosomal aberrations of the MYC gene locus indicate an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL). However, there have been few reports on MYC translocation in Chinese patients. One hundred and six cases of DLBCLs were analyzed using interphase fluorescent in situ hybridization. Immunophenotyping analysis (CD20, CD3, CD10, Bcl-6, Mum-1) was also performed. MYC translocation was identified in 13 (12.3%) out of 106 cases. All MYC(+) DLBCLs showed a non-germinal center B-cell type. MYC(+) DLBCLs showed significantly poorer overall survival (OS) and progression-free survival, with a median OS and progression-free survival time of 4.7 and 3.2 months, respectively (p < 0.001). Multivariate analysis using a Cox proportional hazard model confirmed that MYC(+) (for OS, Hazards ratio 5.254; 95% CI, 2.354-11.723, p < 0.001) was the strongest independent predictor. DLBCL with MYC translocation is a subgroup of non-germinal center B-cell DLBCL with poor outcome. This may be a clinical characteristic that is specific to Chinese patients. Because only a few patients received rituximab, its usefulness could not be assessed. Future studies with larger numbers of patients are required.

[Significance of CD138 in immunohistochemical profiles and its correlation with prognosis in diffuse large B-cell lymphoma].

OBJECTIVE: The purpose of this study was to classify the diffuse large B-cell lymphoma (DLBCL) into different prognostic subgroups according to four different detection methods of the expression of CD138, CD10, bcl-6, and MUM1. In particular to investigate the significance of CD138 in immunohistochemical profiles and its correlation with prognosis in DLBCL. METHODS: Immunohistochemical EnVision method was used to detect the expression of CD138, CD10, bcl-6 and MUM1 in 106 cases of DLBCL and reconstructed into four different subtyping algorithms. Algorithm-1, according to the expression of CD10, bcl-6 and MUM1, the cases were assigned to GCB and non-GCB groups. Algorithm-2, according to the expression of CD138, CD10, bcl-6 and MUM1, the cases were assigned to A, B, C, D groups. Algorithm-3, according to the expression of CD10 and MUM1, the cases were assigned to GCB and non-GCB groups. Algorithm-4, according to the expression of CD138, CD10, bcl-6 and MUM1, the cases were assigned to GCB and non-GCB groups. Following up was included as well. Statistical analysis was performed using the SPSS 13.0 and differences were considered significant at P < 0.05. RESULTS: CD138, MUM1, CD10 and bcl-6 were positive in 15.1% (16/106), 56.6% (60/106), 21.7 (23/106) and 26.4% (28/106), respectively. The expression of CD10 and bcl-6 was associated with favorable OS (P = 0.001 and 0.041, respectively), whereas the expression of CD138 was associated with unfavorable OS (P = 0.003). Using multivariate Cox proportional hazards regression analysis, algorithm-1 and -4 were almost at the same level for prognosis of OS (OR = 0.259, 0.255) and PFS (OR = 0.248, 0.244). CONCLUSIONS: Both Hans's algorithm and Colombo's algorithm including CD138 detection are associated with the prognosis of DLBCL patients. The two algorithms have similar OR value according to Cox analysis. However, positive expression of CD138 is of minor significance in prediction of the prognosis in DLBCL patients.

Clinical Impact of t(14;18) in Diffuse Large B-cell Lymphoma.

OBJECTIVE: Recent studies have suggested that t(14;18) is present in a significant proportion of diffuse large B-cell lymphomas (DLBCLs). However, the prognostic significance of this translocation and its relationship with BCL-2 protein expression remains controversial. Our study aimed to investigate the predictive power of t(14;18) and BCL-2 protein expression in the prognosis of DLBCLs. METHODS: Biopsy specimens from 106 DLBCLs were analyzed using interphase fluorescence in situ hybridization (FISH). Immunophenotypic analysis of CD20, CD3, CD10, BCL-6, MUM1 and BCL-2 was performed by immunohistochemistry. SPSS 13.0 software was used for statistical analysis. RESULTS: The t(14;18) was identified in 27 of 106 cases (25.5%). The percentages of tumor cells expressing CD10, BCL-6, MUM1 and BCL-2 were 21.7%, 26.4%, 56.6% and 73.6%, respectively. The presence of this translocation was significantly correlated with the expression of CD10 and immunophenotypic subtype (p<0.001). No association was observed between BCL-2 protein expression and the presence of t(14;18). Multivariate analysis confirmed that both t(14;18) and BCL-2 expression were significantly associated with survival. Moreover, patients with t(14;18) had worse prognosis, compared with those with BCL-2 expression (for overall survival: hazard ratio, 4.235; 95%CI, 2.153-8.329, p<0.001 vs. hazard ration, 2.743; 95%CI, 1.262-5.962, p=0.011). CONCLUSIONS: The t(14;18) is a useful prognostic tool for the evaluation of DLBCL immunophenotype and prognosis. The prognosis of GCB (germinal centre-like B cell) DLBCL patients should be made with the consideration of the presence of this translocation, and the detection of t(14;18) should be included as a routine diagnostic test in these cases.

[Correlation of Bcl-2 with immunological subtype and prognosis in diffuse large B-cell lymphoma.].

OBJECTIVE: To investigate the Bcl-2 protein and gene expression in diffuse large B-cell lymphoma (DLBCL), and analyze its correlation with immunosubtype and prognosis. METHODS: Seventy-three cases of DLBCL were performed immunohistochemistry analysis with a panel of antibodies CD3, CD10, CD20, Bcl-6, Bcl-2 and MUM-1, and classified into germinal center B-cell (GCB) type and non-GCB type. Fluorescence in situ hybridization (FISH) was employed to detect bcl-2 gene expression in 57 cases with chromosome translocation t (14;18). RESULTS: The percentages of tumor cells expressed CD10, Bcl-6, MUM-1 and Bcl-2 were 15.1%, 38.4%, 71.2% and 79.2%, respectively. 16 cases (21.9%) were GCB type and the rest (78.1%) were non-GCB type. 16 of 57 cases (28.1%) were t (14; 18), including 5 of GCB type (31.2%) and 11 of non-GCB type (68.2%). The expression of Bcl-2 protein was correlated with immunological subtype (P = 0.035), but not with survival time (P = 0.253). Between the t(14;18) positive and negtive groupes, there was significant difference for survival time (P = 0.022), but no difference for immunological subtype (P = 0.340). There was no correlation between Bcl-2 protein and t(14;18). CONCLUSIONS: GCB type DBLBCL with expression of Bcl-2 protein had a poor prognosis. t(14; 18) positive BLBCL had poor prognosis. The expression of Bcl-2 protein and t(14; 18) are usually discordant.

[State of chromosome 3q27 and different subtypes of diffuse large B-cell lymphoma and their prognostic correlation].

OBJECTIVE: To study the immunophenotypic and genetic features of diffuse large B-cell lymphomas (DLBCLs), and their relationship to prognosis. METHODS: Seventy-three cases of DLBCLs with follow-up data were studied by using immunohistochemistry for CD3, CD10, CD20, bcl-6 and MUM-1. 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. Fluorescence in-situ hybridization (FISH) for bcl-6 gene expression (located on chromosome 3q27) was performed on paraffin-embedded tissues of 54 cases. RESULTS: In the 73 cases studied, 16 cases (21.9%) belonged to GCB subtype and 57 cases (78.1%) belonged to non-GCB subtype. Breakage of 3q27 was detected in 11 of the 54 cases (20.4%) and proliferation was detected in 14 cases (25.9%). The five-year overall survival rate of GCB subtype was significantly higher than that of non-GCB subtype (78% versus 40%, P = 0.011). The bcl-6-positive cases had a better clinical outcome than that of the bcl-6-negative cases (P = 0.041). Breakage of 3q27 predicted a worse overall survival. CONCLUSIONS: The current study shows that the prognosis of GCB subtype of DLBCLs is better than that of non-GCB subtype. The expression of bcl-6 protein predicts a better clinical outcome, while the breakage of 3q27 predicts a worse overall survival.