CD10 and Bcl-2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large-cell lymphoma with very good or very poor prognoses

AIMS: Diffuse large B-cell lymphoma (DLBCL) is characterized by marked biological heterogeneity. The identification of reproducible parameters that can be combined with the International Prognostic Index (IPI) to better predict outcome could lead to the development of effective risk-adaptive strategies. METHODS AND RESULTS: Bcl-2 and CD10 expression was determined by immunohistochemistry. The impact of the positivity on survival was evaluated in combination with the IPI in 86 patients with a confirmed diagnosis of DLBCL. Patients were divided according to the IPI into low-risk (no to two factors) or high-risk (three to five factors) groups. Positivity rates were 25% for CD10 and 42% for Bcl-2. In a Cox analysis, the high-risk IPI group [hazard ratio (HR) 5.98, P < 0.0001) and Bcl-2 expression (HR 2.43, P = 0.02) were independent poor prognostic factors, and expression of CD10 (HR 0.41, P = 0.052) predicted a favourable outcome. Among patients in the low-risk IPI group, CD10 positivity was associated with an excellent 8-year overall survival (92% versus 45%, P = 0.06). In the high-risk IPI group, Bcl-2 positivity identified a subgroup with invariably fatal disease. CONCLUSIONS: The expression of CD10 in the low-risk IPI group, and the expression of Bcl-2 in the high-risk IPI group can identify two subgroups of patients who might benefit from new risk-adaptive treatment approaches.     

Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma.

We sought to determine whether identification of poor-risk subgroups of diffuse large B-cell lymphoma (DLBCL) using immunohistochemical stains would have practical utility with regard to prognosis and therapeutic decisions. Tissue microarray blocks were created using replicate samples of formalin-fixed, paraffin-embedded tissue from 200 cases of de novo DLBCL. The sections were stained with antibodies to proteins that are expressed by activated or proliferating B cells including MUM1, FOXP1, bcl-2, survivin, protein kinase C-beta (PKC-beta), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P = 0.025) or PKC-beta (P = 0.015) was associated with a worse overall survival, whereas none of the other markers was predictive of overall survival. Patients with DLBCL that expressed either cyclin D2 or PKC-beta had a 5-year overall survival of only 30% as compared to 52% for those who were negative for both markers (P = 0.0019). In multivariate analysis, the expression of cyclin D2 or PKC-beta was an independent predictor of poor overall survival (P = 0.035). Cyclin D2 and PKC-beta expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.     

CD10 and Bcl10 expression in diffuse large B-cell lymphoma: CD10 is a marker of improved prognosis

AIMS: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically and pathologically heterogeneous. The Bcl10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosa-associated lymphoid tissue (MALT) lymphomas, and is considered to be an apoptosis-associated gene. CD10 is considered to be a marker of follicular centre B-cell differentiation. To assess the clinical significance and roles of CD10 and Bcl10 in DLBCL, we analysed 138 cases, using immunohistochemical methods. METHODS AND RESULTS: CD10 expression was limited to the cytoplasm, whereas Bcl10 expression was detected in the cytoplasm and/or nuclei. CD10 expression was detected in 39 of 138 cases (28.2%), cytoplasmic Bcl10 in 68 cases (49.2%), and nuclear Bcl10 in 34 cases (24.6%). Nuclear Bcl10 was detected in 14 of 28 cases (50%) of extranodal DLBCL, but only 20 of 110 cases (18.2%) of nodal DLBCL. Cytoplasmic Bcl10 was detected in 19 of 28 cases (67.8%) of extranodal DLBCL and 49 of 110 cases (44.5%) of nodal DLBCL. CD10 expression closely correlated with improved survival (68% overall survival (OS) vs. 48% OS), but not with site of disease. A high International Prognostic Index (IPI) was considered to be a poor prognostic factor associated with a shorter OS. CD10 expression was detected in 27 of 84 cases (32.1%) with low-risk IPIs, and in 12 of 54 cases (22.2%) with high-risk IPIs. In the low-risk group, cases expressing CD10 carried a better prognosis than CD10- cases (93% OS vs. 71% OS), whereas this was not the case in the high-risk group (25% vs. 20%). CONCLUSIONS: Bcl10 expression was associated with extranodal DLBCL, but not with prognosis. CD10 expression was closely associated with improved survival, but not with risk as predicted by IPI. Overall, our results suggest that CD10 expression may be useful, in combination with clinical parameters, for determining the prognosis of DLBCL.     

弥漫大B细胞淋巴瘤免疫表型分型与预后的关系

目的 探讨弥漫大B细胞淋巴瘤（DLBCL）的免疫表型之生发中心B细胞样（GCB）和非GCB两个亚型的特征及其与DLBCL预后的关系。方法 根据肿瘤细胞免疫组织化学EnVision法标记CD10、bc1-6、MUM-1的表达情况,将133例DLBCL分为GCB和非GCB两个亚型。对以下指标的5年总生存率（OS）及5年无进展生存率（PFS）进行了比较：（1）CD10、bc1-6和MUM-1的阳性和阴性病例;（2）GCB亚型与非GCB亚型;（3）不同国际预后指数（IPI）分组中GCB亚型与非GCB亚型的关系。结果 133例DLBCL中,44例（33．1％）CD10阳性,48例（34．6％）bc1-6阳性,60例（45．1％）MUM-1阳性。CD10阳性DLBCL患者的5年OS及PFS均明显高于CD10阴性患者（P=0．041和0．031）;bc1-6阳性DLBCL患者的PFS明显高于bc1-6阴性患者（P=0．044）,MUM．1阳性DLBCL患者的5年0s及PFS均明显低于MUM-1阴性患者（P=0．031和0．028）。GCB型54例（40．6％）,非GCB型79例（59．4％）。GCB型5年OS及PFS均明显高于非GCB型（P=0．004和0．003）。国际预后指数（IPI）0-1分组及2-5分组中,GCB型5年OS及PFS均明显高于非GCB型（IP10-1分组P=0．019和0．014,2-5分组P=0．006和0．009）,其中IPI2-5分组中的非GCB预后最差。结论 DLBCL亚型及其与IPI联合分析可以作为预测患者预后的有效指标。     

Is CONUT score a prognostic index in patients with diffuse large cell lymphoma?

Background/aimThe aim of the study was to evaluate the effect of Controlling Nutritional Status (CONUT) score on the prognosis in patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods The present study was a retrospective study. The CONUT score was calculated based on serum albumin, total cholesterol and lymphocyte levels. This study included a total of 266 patients, 131 (49.2%) were female and 135 (50.8%) were male. The median follow-up period was 51 months (range: 1–190).Results The median age was 64 years. The cut off CONUT was 1.5. There was a significant difference between patients with high (≥ 2) or low (< 2) CONUT scores in terms of overall survival (OS) and progression-free survival (PFS). The 5-year OS and PFS in patients with high CONUT score was 52.1% and 49.7%. The 5-year OS and PFS in patients with low CONUT score was 79.8% and 75.6% (p < 0.001). In the multivariate analysis for OS, age ≥ 65 years (HR = 1.80, p = 0.028), Eastern Cooperative Oncology Group (ECOG) > 1 (HR = 2.04, p = 0.006), stage IIIA–IVB disease (HR = 2.75, p = 0.001) and the CONUT score (HR = 1.15, p = 0.003) were found statistically significant. In the multivariate analysis for PFS, age ≥ 65 years (HR = 2.02, p = 0.007), stage IIIA–IVB disease (HR = 2.42, p = 0.002) and the CONUT score (HR = 1.19, p = 0.001) were found to be significant parameters. ConclusionHigh CONUT score reduces OS and PFS in DLBCL. CONUT score is an independent, strong prognostic index in patients with DLBCL.     

Clinicopathological and prognostic significance of microRNA-107 in human non small cell lung cancer

Background: MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. Researchers have found that the expression level of miR-107 was decreased in human non-small cell lung cancer (NSCLC) tissues and cell lines, however, its clinicopathological and prognostic significance in NSCLC has not been investigated. Methods: Quantitative real-time PCR (qRT-PCR) was used to analyze the expression of miR-107 in 137 pairs of fresh NSCLC and matched adjacent normal tissue specimens. The chi-square test and Fishers exact tests were used to examine the associations between miR-107 expression and the clinicopathological characters. The overall survival (OS) and progression-free survival (PFS) were analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. Results: The expression level of miR-107 was significantly lower in tumor tissues than that in corresponding noncancerous tissues (0.4676±0.2078 vs. 1.000±0.3953, P<0.001). Low expression of miR-107 was found to significantly correlate with TNM stage (p=0.001), regional lymph node involvement (p=0.04), and tumor differentiation (p=0.003). Kaplan-Meier analysis with the log-rank test indicated that low miR-107 expression had a significant impact on OS (35.2% vs. 69.3%; P=0.008) and PFS (30.0% vs. 56.2%; P=0.029). In a multivariate Cox model, we found that miR-107 expression was an independent poor prognostic factor for both 5-year OS (HR=2.57, 95% CI: 1.88-10.28; P=0.007) and 5-year PFS (HR=3.08, 95% CI: 2.01-8.92; P=0.003). Conclusion: The expression of miR-107 was decreased in NSCLC. Low expression of miR-107 was significantly associated with tumor progression and decreased survival in patients with NSCLC, indicating that miR-107 may serve as a novel prognostic marker in NSCLC.     

Red blood cell distribution width as a simple negative prognostic factor in patients with diffuse large B-cell lymphoma: a retrospective study

AimTo determine the prognostic value of baseline red blood cell distribution width (RDW) in diffuse large B cell lymphoma (DLBCL) patients.MethodsData from 81 DLBCL patients diagnosed from 2006 to 2013 at the University Hospital Center Osijek, Osijek, Croatia, were reviewed. We evaluated disease outcome, overall survival (OS) and event-free survival (EFS), and demographic, clinical and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used.ResultsMedian age of patients was 64 years, 29 were men (35.8%). Higher RDW levels (%) were found in patients with advanced Ann Arbor clinical stage (14.94 ± 1.82 vs 13.55 ± 1.54, P = 0.001) and in those with poor response to therapy (14.94 ± 1.82 vs 13.55 ± 1.54, P = 0.001). Patients with RDW>15% (cut-off was calculated by receiver operating characteristics) had significantly worse OS (median [range], 33 months [20-46] vs 74 months [65-82], P < 0.001) and EFS (27 months [15-40] vs 68 months [59-77], P < 0.001). Cox regression analysis showed that RDW>15% was an independent prognostic factor for OS (HR 3.654, 95% CI 1.128-11.836) and EFS (HR 2.611, 95% CI 1.012-6-739).ConclusionHigh baseline RDW is an independent prognostic marker of poor outcome in patients with DLBCL. RDW could be an easily available and inexpensive marker for the risk stratification in patients with DLBCL.Red cell distribution width (RDW) is analyzed routinely as part of the complete blood count (CBC). It is a measure of heterogeneity of the red blood cell (RBC) size and traditionally has played a role in the differential diagnosis of anemia (1). High RDW values are associated with increased mortality in general population and in patients with cardiovascular disease, sepsis, acute kidney injury, chronic obstructive pulmonary disease, hepatitis B, and those on chronic dialysis (2-9). There is also evidence of its prognostic value in various malignancies (10-14). A recent study found a strong relation between high RDW and poor survival in patients with lung cancer (15). RDW was also found to be a significant predictor of poor prognosis in patients with malignant mesothelioma (16). In patients with symptomatic multiple myeloma, elevated RDW values were associated with a higher stage disease according to International Staging System and poor prognosis (17). The mechanism that could explain the relation between RDW and survival or disease activity is not clear, but it is considered that high RDW is caused by chronic inflammation, poor nutritional status, oxidative stress, and age-related diseases that lead to changes in erythropoiesis (2,18-20).Diffuse large B-cell lymphoma (DLBCL) is the most common group of lymphomas, amounting to 25% of all non-Hodgkin’s lymphomas (NHL) (21). It is a type of aggressive lymphoma that usually affects middle-aged and elderly patients. The distribution of NHL subtypes in Croatia corresponds to the European average (22). The most commonly used prognostic index in aggressive NHL is the international prognostic index (IPI) and its variants used in elderly patients (age-adjusted IPI) and in patients treated with rituximab (R-IPI) (23,24).So far, there have been no reports on the prognostic value of RDW in patients with DLBCL. The aim of our study was to determine whether RDW measured at diagnosis was an independent prognostic factor of disease outcome, overall survival (OS), and event-free survival (EFS) in patients with DLBCL.     

Prognostic clinicopathologic factors, including immunologic expression in diffuse large B-cell lymphomas

The aim of this study was to assess the clinical significance and potential prognostic value of the expression of a panel of surface markers, proliferating, suppressor and oncogenic proteins in diffuse large B-cell lymphomas (DLBCL). Biopsies were collected from 158 patients with DLBCL and analyzed immunohistochemically for p53, p21/WAF1, bcl-2, cyclin-D1, bcl-6, mdr, CD5, CD30, epithelial membrane antigen (EMA), Ki-67 and c-myc positive tumor cells. Among these, 76 young and middle-aged patients (20-65 years) were selected to investigate the relationship between protein expression, clinical features, and survival. Survival analysis showed that advanced stage, high lactic dehydrogenase level, and high International Prognostic Index (IPI) were poor prognostic factors associated with a shorter overall survival (OS) and disease-free survival (DFS) times. A high p53 expression and low bcl-6 expression were associated with a shorter DFS time. The histological variant type, cyclin-D1+ CD5+ DLBCL, positive epithelial membrane antigen (EMA+) CD30- DLBCL, high bcl-2 expression, and low Ki-67 proliferation activity tended to be associated with worse survival, but the correlations were not statistically significant. In the multivariate analysis, the most significant factors were age, followed by IPI and last p53. The expression of p21/WAF1, mdr, and c-myc proteins did not influence OS and DFS. The expression of p53 and bcl-6 proteins may be useful prognostic indicators in DLBCL. Cyclin-D1+ CD5+ or EMA+ CD30- DLBCL tended to predict a worse survival and may probably bear a significant prognostic value worthy of consideration. Overall, clinical factors appeared to be more important than biologic parameters in determining the prognosis of diffuse large B-cell lymphomas.     

Gene expression of BAALC, CDKN1B, ERG, and MN1 adds independent prognostic information to cytogenetics and molecular mutations in adult acute myeloid leukemia

Expression of BAALC, ERG, and MN1 is associated with outcome in normal karyotype acute myeloid leukemia (AML). In this study, the expression of these markers and of EVI1 and CDKN1B was determined using oligonucleotide microarrays in 286 AML comprising all cytogenetic groups. Higher expression of each gene was associated with an inferior outcome: CDKN1B, median overall survival (mOS): 14.9 months vs. not reached (nr), P = 0.005, median event-free survival (mEFS): 9.7 vs. 31.0 months, P = 0.013; BAALC, no impact on OS, mEFS: 6.2 vs. 13.0 months, P = 0.03; ERG: mOS: 12.5 months vs. nr, P = 0.002, mEFS: 8.1 vs. 15.7 months, P = 0.001; MN1: mOS: 12.3 months vs. nr, P = 0.004, mEFS: 8.1 vs. 16.7 months, P = 0.001. A multivariate analysis revealed an independent impact on OS for CDKN1B, ERG, and MN1 expression. A novel score based on BAALC, CDKN1B, ERG, and MN1 expression had an impact on OS and EFS independent of cytogenetics and age. A score taking into account gene expression and karyotype allowed the separation of four prognostic groups with significant differences in OS and EFS (OS at 2 years: 90.4%, 56.4%, 34.0%, 12.6%; mEFS: n.r., 18.1 months, 8.7 months, 2.5 months). The impact on outcome of this score was independent of NPM1mut/FLT3-ITD- status, MLL-PTD, and age.     

Primary systemic anaplastic large cell lymphoma in Korean adults: 11 years' experience at Asan Medical Center

PURPOSE: Anaplastic large cell lymphoma (ALCL), a CD30+ T-cell non-Hodgkin's lymphoma, represents only 2-8% of lymphoma overall. Information on the clinical findings of primary systemic ALCL in Korea is limited. Our aims were to report the clinical features and outcomes of primary systemic ALCL. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 36 adult patients diagnosed with primary systemic ALCL at Asan Medical Center from February 1995 through June 2006. RESULTS: Of 36 patients, 29 were male. The median age was 39 years (range, 17-67 years), and 26 (72%) presented with Ann Arbor stages III and IV. The most commonly involved extranodal sites were bone (n = 7) and soft tissue (n = 6). Thirty-two of all patients (89%) were treated with an anthracycline-based regimen including cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) as induction chemotherapy; 16 (50%) achieved complete remission (CR), and 13 (41%) achieved partial remission (PR). Median overall survival (OS) and event-free survival (EFS) were 49 and 17 months, respectively. Univariate analysis showed that performance status (p = 0.035), international prognostic index (IPI) (p = 0.025), and age-adjusted IPI (p = 0.034) were significant prognostic factors for OS, whereas anaplastic lymphoma kinase (ALK) expression did not affect OS (p = 0.483). CONCLUSION: Our retrospective analysis of Korean primary systemic ALCL patients showed that median OS was 49 months and overall response to CHOP was 91%. Performance, IPI, and age-adjusted IPI were predictors of OS, whereas ALK expression did not have prognostic significance.     

Prognostic value of circulating tumor DNA in lymphoma: a meta-analysis

Circulating tumor DNA (ctDNA) can be used to evaluate the prognosis of lymphoma. However, there is no uniform consensus about the mechanistic role that ctDNA plays in the prognosis of lymphoma. This meta-analysis explores the prognostic value of ctDNA in lymphoma, especially in diffuse large B cell lymphoma (DLBCL). All relevant reports published as of May 14, 2020, were retrieved by searching electronic databases in Pubmed, Embase and Cochrane Library. The prognostic value of ctDNA was evaluated using meta-analysis. Revman 5.3 software was used for prognostic data extraction and analysis. Eight studies, including a total of 767 lymphoma patients, were enrolled in this meta-analysis. Five out of eight studies investigated the association between ctDNA levels and progression-free survival (PFS) in 501 lymphoma patients, indicating that high levels of ctDNA were significantly associated with poor PFS (HR 2.24, 95%CI: 1.63–3.08, P?<?0.00001). We conducted a subgroup analysis of 379 patients with DLBCL across three of the studies and came to the same conclusion (HR 2.01, 95%CI: 1.42–2.85, P?<?0.0001). Two studies with a total of 192 lymphoma patients described the association between ctDNA levels and event-free survival (EFS), showing that high levels of ctDNA were also associated with adverse EFS (HR 4.53, 95%CI: 1.79–11.47, P?=?0.001). The remaining two studies analyzed the potential clinical value of ctDNA for predicting the overall survival time (OS) of DLBCL patients, demonstrating that high levels of ctDNA correlated with inferior OS (HR 3.09, 95%CI: 1.50–6.35, P?=?0.002). Our meta-analysis showed that high levels of ctDNA were associated with poor prognosis in patients with lymphoma, especially DLBCL.

     

Upfront Consolidation Combining Yttrium-90 Ibritumomab Tiuxetan and High-Dose Therapy with Stem Cell Transplantation in Poor-Risk Patients with Diffuse Large B Cell Lymphoma

We evaluated the safety and efficacy of standard-dose yttrium-90 (Y⁹⁰) ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma (DLBCL) (clinicaltrials.gov: NCT00689169). Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y⁹⁰ ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of >500/μL and platelet count of >20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus >2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y⁹⁰ ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. First-line consolidation with Y⁹⁰ ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET status after induction treatment and warrants a randomized study.     

Prognostic value of CD133 expression in stage I lung adenocarcinomas

CD133 is one of the most representative cancer stem cell markers. This study evaluated the potential prognostic value of CD133 expression in stage I lung adenocarcinomas (ADC). Tumors from 177 patients were immunohistochemically examined for CD133 expression, and their associations with disease recurrence were analyzed. Also, the potential prognostic value of combining CD133 expression with proliferating activity measured by immunohistochemical expression of Ki-67 and vessel involvement was evaluated. CD133 high expressers showed a significantly higher risk of recurrence than CD133 low expressers: 5-year disease-free survival (DFS) rate 77.2% vs. 95.1% (p=0.004), adjusted Hazard ratio (HR) 4.37, 95% Confidence Interval (CI) 1.30-14.71 (p=0.017). CD133 high expressers having strong proliferating activity and/or with vessel invasion showed a higher risk of recurrence: 5-year DFS rate 66.5% in CD133 high/Ki-67 high expressers vs. 93.2% in the other types (p<0.001), adjusted HR 8.39, 95% CI 2.65-26.54 (p<0.001): 5-year DFS rate 51.0% in CD133 high expressers with vessel invasion vs. 92.9% in the other types (p<0.001), adjusted HR 4.50, 95% CI 1.51-13.34 (p=0.007): 5-year DFS rate 53.9% in CD133 high/Ki-67 high expressers with vessel invasion vs. 91.2% in the other types (p<0.001), adjusted HR 9.32, 95% CI 3.42-25.39 (p<0.001). In conclusion, the level of CD133 expression is an independent prognostic marker and its combination with proliferating activity and/or vessel invasion could have excellent prognostic value to predict postoperative recurrence in patients with stage I lung ADC.     

Immunohistochemical algorithm alone is not enough for predicting the outcome of patients with diffuse large B-cell lymphoma treated with R-CHOP

Gene expression profiling (GEP), which can divide DLBCL into three groups, is impractical to perform routinely. Although algorithms based on immunohistochemistry (IHC) have been proposed as a surrogate for GEP analysis, the power of them has diminished since rituximab added to the chemotherapy. We assessed the prognostic value of four conventional algorithms and the genes in each and out of algorithm by IHC and fluorescence in situ hybridization in DLBCL patients receiving immunochemotherapy. The results showed that neither single protein within algorithms nor the IHC algorithms themselves had strong prognostic power. Using MYC aberrations (MA) either on the genetic or protein levels, we established a new algorithm called MA that could divide patients into distinct prognostic groups. Patients of MA had much shorter overall survival (OS) and progression-free survival (PFS) than non-MA (2-year OS: 56.9% vs. 98.7%; 2-year PFS: 26.8% vs. 86.9%; P < 0.0001 for both). In conclusions, using additional prognostic markers not associated with cell of origin may accurately predict outcomes of DLBCL. Studies with larger samples should be performed to confirm our algorithm and optimize the prognostic system of DLBCL.     

The role of gender in patients with diffuse large B cell lymphoma treated with rituximab-containing regimens: a meta-analysis

Introduction

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). Although gender has not been included in prognostic systems, male gender has been found as a bad prognostic indicator in Hodgkin lymphoma, follicular lymphoma and chronic lymphocytic leukemia. The relationship between gender and prognosis is not clear in patients with DLBCL treated with rituximab-containing regimens. The aim of this meta-analysis is to determine the prognostic/predictive role of gender in patients with DLBCL treated with rituximab-containing regimens.

Material and methods

We systematically searched for studies investigating the relationships between gender and prognosis in DLBCL treated with rituximab-containing regimens. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival, disease-free survival (DFS) and event-free survival (EFS).

Results

A total of 5635 patients from 20 studies were included in the analysis. Our results showed that male gender was associated with poor prognosis in terms of overall survival (OS) (hazard ratio (HR) = 1.155; 95% confidence interval (CI): 1.037–1.286; p < 0.009). The pooled hazard ratio for DFS and EFS showed that male gender was not statistically significant (HR = 1.219; 95% CI: 0.782–1.899; p = 0.382, HR = 0.809; 95% CI: 0.577–1.133; p = 0.217).

Conclusions

The present meta-analysis indicated male gender to be associated with a poor prognosis in patients with DLBCL treated with rituximab-containing regimens.     

弥漫大B细胞性淋巴瘤survivin表达与其预后的关系

目的探讨弥漫大B细胞淋巴瘤survivin表达与临床表现的关系。方法收集有完整随访资料的弥漫大B细胞性淋巴瘤（diffuselargeB—celllymphoma,DLBCL）患者128人,均有5年以上完整的随访资料。用免疫组化SP法检测其survivin表达情况,并分析其表达与临床预后的关系。结果128例DLBCL患者中有84例survivin蛋白表达阳性,阳性率为65．6％。表达阳性者与阴性者5年（overallsurvival,OS）分别为58．8％和18．7％,差异具有统计学意义。在淋巴瘤国际预后指数（internationalprognosticindex,IPI）积分低危患者中,survivin表达阳性者5年总生存期OS及无病生存期（diseasefreesurvival,DFS）明显低于表达阴性者：在国际预后指标（internationalprognosisindex,IPI）积分高危患者中,survivin表达阳性与阴性者5年0s无明显差异。结论Survivin是DLBCL的一个较有价值的预后指标,与IPI联合应用可筛选出低危患者中预后不良病例。     

Absence of cyclin-D2 and Bcl-2 expression within the germinal centre type of diffuse large B-cell lymphoma identifies a very good prognostic subgroup of patients

AIMS: To validate and improve the existing algorithm (proposed by Hans et al.) to classify diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS: Tissue microarrays constructed from 81 patients with DLBCL were studied by immunohistochemistry for expression of CD10, Bcl-6, MUM1, Bcl-2, cyclin-D2, FOXP1 and PKC-gamma proteins. Cases were classified as either germinal centre B-like (GCB) or non-GC according to Hans et al. An alternative classification was also employed, in which cases positive for either CD10 or Bcl-6 were considered as a GC subgroup and cases negative for both CD10 and Bcl-6 were considered as a non-GC subgroup. GC was further subdivided into favourable GC (negative for both Bcl-2 and cyclin-D2) and unfavourable GC (positive for either Bcl-2 or cyclin-D2). The 5-year event-free survival (EFS) amongst patients classified as favourable GC versus 'others' was 49.5% and 7.3%, respectively (log rank P < 0.0001). Similarly, the 5-year overall survival (OS) amongst patients classified as favourable GC versus 'others' was 58.6% and 13.7%, respectively (log rank P = 0.0001). The difference in survival was independent of the international prognostic index. CONCLUSIONS: In this group of patients the risk stratification based on the new algorithm was better than that proposed by Hans et al.     

Prognostic value of CD133 expression in stage I lung adenocarcinomas

CD133 is one of the most representative cancer stem cell markers. This study evaluated the potential prognostic value of CD133 expression in stage I lung adenocarcinomas (ADC). Tumors from 177 patients were immunohistochemically examined for CD133 expression, and their associations with disease recurrence were analyzed. Also, the potential prognostic value of combining CD133 expression with proliferating activity measured by immunohistochemical expression of Ki-67 and vessel involvement was evaluated. CD133 high expressers showed a significantly higher risk of recurrence than CD133 low expressers: 5-year disease-free survival (DFS) rate 77.2% vs. 95.1% (p=0.004), adjusted Hazard ratio (HR) 4.37, 95% Confidence Interval (CI) 1.30-14.71 (p=0.017). CD133 high expressers having strong proliferating activity and/or with vessel invasion showed a higher risk of recurrence: 5-year DFS rate 66.5% in CD133 high/Ki-67 high expressers vs. 93.2% in the other types (p<0.001), adjusted HR 8.39, 95% CI 2.65-26.54 (p<0.001): 5-year DFS rate 51.0% in CD133 high expressers with vessel invasion vs. 92.9% in the other types (p<0.001), adjusted HR 4.50, 95% CI 1.51-13.34 (p=0.007): 5-year DFS rate 53.9% in CD133 high/Ki-67 high expressers with vessel invasion vs. 91.2% in the other types (p<0.001), adjusted HR 9.32, 95% CI 3.42-25.39 (p<0.001). In conclusion, the level of CD133 expression is an independent prognostic marker and its combination with proliferating activity and/or vessel invasion could have excellent prognostic value to predict postoperative recurrence in patients with stage I lung ADC.     

Prognostic value of microRNA-451 in various cancers: A meta-analysis

BackgroundIncreasing evidence shows microRNA-451 plays a crucial role in various tumors, but there is inconsistency. The aim of this study was to explore the prognostic role of miR-451 in various tumors.MethodsOnline PubMed, EMBASE, Web of Science, and the Cochrane library database were searched through February 2019. Hazard ratios (HRs) were extracted and used to describe the association between expression of microRNA-451 and survival outcome, and the correlation between microRNA-451 and clinicopathologic features were described by pooled odds ratios (ORs).ResultsSixteen retrospective studies containing 2122 patients were incorporated in this meta-analysis. High expression of miR-451 was considered statistically associated with prolonged overall survival (OS) (HR = 0.62, 95% CI 0.49-0.80, p < 0.001) as well as RFS/DFS (HR = 0.55, 95% CI 0.42-0.71, p < 0.001) compared with low expression of miR-451. Besides, the pooled ORs revealed significant association between high expression of miR-451 with lymph node invasion (yes vs. no) (OR = 0.64, 95% CI 0.46-0.90, P = 0.01), tumor diameter (big vs. small) (OR = 0.77, 95% CI 0.60-0.97, P = 0.028) and tumor stage (III + IV vs. I + II) (OR = 0.62, 95% CI 0.42-0.93, P = 0.019).ConclusionMicroRNA-451 may serve as a promising clinical prognostic biomarker in various carcinomas.