Expression of BAFF and BAFF-R in Follicular Lymphoma: Correlation with Clinicopathologic Characteristics and Survival Outcomes

Background

B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between expression levels of BAFF detected by immunohistochemical (IHC) and serum levels of BAFF was also evaluated.

Methods

Paraffin-embedded specimens from 115 patients were immunohistochemically examined for BAFF and BAFF-R expression. Expression levels were dichotomized into low versus high categories based on immunostaining intensity. The correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and patient outcome was assessed. Serum levels of BAFF in 35 of the 115 patients with IHC data were measured by Enzyme-linked Immunosorbent assay (ELISA).

Results

BAFF and BAFF-R were expressed in 88.7% (102/115) and 87.8% (101/115) of the cases, respectively. BAFF expression was significantly correlated with only one clinicopathologic feature: Ann Arbor stage. No significant correlation was found between expression levels of BAFF detected by IHC and serum levels of BAFF detected by ELISA. High expression of BAFF-R, but not BAFF, was significantly correlated with inferior progression-free survival (PFS; P = 0.013) and overall survival (OS; P = 0.03). High expression of BAFF-R, bulky disease, and elevated lactate dehydrogenase were correlated with inferior PFS and OS in multivariate analysis. A prognostic scoring system incorporating these 3 risk factors identified 3 distinct prognostic groups with 5-year PFS of 59.4%, 41.9%, and 10.7% and OS of 91.3%, 79.7%, and 45.8%, respectively.

Conclusions

Most patients with FL variably express BAFF and BAFF-R. High expression of BAFF-R, but not BAFF, may be an independent risk factor for PFS and OS in FL.     

High Pretreatment D-Dimer Levels Correlate with Adverse Clinical Features and Predict Poor Survival in Patients with Natural Killer/T-Cell Lymphoma

Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47–6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL.     

Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab- CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL)

ABSTRACT: BACKGROUND: The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland. METHODS: Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed. RESULTS: Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001). CONCLUSIONS: Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.     

Prognostic significance of Beclin 1 in intrahepatic cholangiocellular carcinoma

Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1 plays important roles in autophagy, differentiation, apoptosis and the development and progression of cancer, but the expression of Beclin 1 and its possible role in primary intrahepatic cholangiocarcinoma (ICC) has not been reported yet. This study aimed to investigate Beclin 1 expression and its prognostic significance in ICC. First, we assessed the expression levels of Becn1 by real-time PCR in 50 ICC samples and found Becn1 mRNA expression was markedly increased in 78% (39 of 50) samples compared with normal bile duct epithelium. Beclin 1 protein expression in 108 tumor specimens from patients diagnosed with ICC was examined by immunohistochemistry and the correlation between Beclin 1 expression and clinicopathological factors were investigated. Immunopositivity for Beclin 1 was found in 72.2% (78 of 108) samples and low Beclin 1 expression was significantly associated with lymph node metastasis. The correlation between Beclin 1 expression and metastasis was validated in 46 ICC samples with lymph node metastasis. In survival analysis, low Beclin 1 expression was associated with worse overall survival (OS; p = 0.025) and disease-free survival (DFS; p = 0.027). In multivariate analysis, Beclin 1 expression, intrahepatic metastasis, lymph node metastasis and tumor size were found to be independent prognostic factors of OS. Thus, our results suggested the expression of Beclin 1 was correlated with progression and metastasis of ICC and it might serve as a novel prognostic marker for patients with ICC.     

Prognostic significance of Beclin 1 in intrahepatic cholangiocellular carcinoma

Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1 plays important roles in autophagy, differentiation, apoptosis and the development and progression of cancer, but the expression of Beclin 1 and its possible role in primary intrahepatic cholangiocarcinoma (ICC) has not been reported yet. This study aimed to investigate Beclin 1 expression and its prognostic significance in ICC. First, we assessed the expression levels of Becn1 by real-time PCR in 50 ICC samples and found Becn1 mRNA expression was markedly increased in 78% (39 of 50) samples compared with normal bile duct epithelium. Beclin 1 protein expression in 108 tumor specimens from patients diagnosed with ICC was examined by immunohistochemistry and the correlation between Beclin 1 expression and clinicopathological factors were investigated. Immunopositivity for Beclin 1 was found in 72.2% (78 of 108) samples and low Beclin 1 expression was significantly associated with lymph node metastasis. The correlation between Beclin 1 expression and metastasis was validated in 46 ICC samples with lymph node metastasis. In survival analysis, low Beclin 1 expression was associated with worse overall survival (OS; p = 0.025) and disease-free survival (DFS; p = 0.027). In multivariate analysis, Beclin 1 expression, intrahepatic metastasis, lymph node metastasis and tumor size were found to be independent prognostic factors of OS. Thus, our results suggested the expression of Beclin 1 was correlated with progression and metastasis of ICC and it might serve as a novel prognostic marker for patients with ICC.     

Autophagic Protein Beclin 1 Serves as an Independent Positive Prognostic Biomarker for Non-Small Cell Lung Cancer

Beclin 1, a key regulator of autophagy, has been found to be aberrantly expressed in a variety of human malignancies. Herein, we employed immunohistochemistry (IHC) to detect the protein expression of Beclin 1 in non-small cell lung cancer (NSCLC) and paired normal adjacent lung tissues, and analyzed its clinicopathological/prognostic significance in NSCLC. Receiver operating characteristic (ROC) curve analysis was utilized to determine a cutoff point (>2 VS. ≤2) for Beclin 1 expression in a training set (n = 105). For validation, the ROC-derived cutoff value was subjected to analysis of the association of Beclin 1 with patients’ clinical characteristics and outcome in a testing set (n = 111) and the overall patient cohort (n = 216). Our data showed that Beclin 1 was significantly lower in NSCLC tissues compared with the adjacent normal tissues, negatively associating with tumor recurrence rate (65.8% VS 32.3%; p < 0.001). In the testing set and the overall patient cohort, low expression of Beclin 1 showed significantly inferior overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) compared to high expression of Beclin 1. In the testing set and the overall patient cohort, the median duration of OS for patients with high and low expression of Beclin 1 was 108 VS. 24.5 months (p < 0.001) and 108 VS. 28 months (p < 0.001), respectively. Furthermore, low expression of Beclin 1 was also a poor prognostic factor within each stage of NSCLC patients. Multivariate analysis identified that Beclin 1 was an independent prognostic factor for NSCLC. Our findings in the present study provided evidence that Beclin 1 may thus emerge as an independent prognostic biomarker in this tumor entity in the future.     

MUM1、UBE1在弥漫性大B细胞淋巴瘤中的表达及意义

目的探讨MUM1、UBE1在弥漫性大B细胞淋巴瘤（DLBCL）中的表达及预后判断中的应用价值。方法对80例DLBCL,NOS标本,采用免疫组织化学EnVision二步法检测MUM1和UBE1的表达,并与临床资料比较。结果MUM1、UBE1在DLBCL中表达的阳性率分别为62．5％（50／80）及65％（52／80）,MUM1及其与UBE1同时表达时与患者的Ann Arbor分期、年龄、结外侵犯部位数目、LDH水平及国际预后指数的危险度均相关（P〈0．05）;生存分析显示MUM1及其与UBE1同时表达时,生存率较低。结论MUM1在DLBCL中高表达提示预后不良,特别是在同时出现UBE1高表达时更显著;MUM1和UBE1同时高表达可作为判断患者预后的重要指标。     

Evaluation of different staging systems and prognostic analysis of nasal-type extranodal NK/T-cell lymphoma based on consistent LVDP chemotherapy regimen

Nasal-type extranodal NK-T-cell lymphoma (ENKTL) is a rare non-Hodgkin lymphoma. The optimal staging system for it remains undefined. In this study, we evaluated different staging systems in 205 patients with nasal-type ENKTL based on a consistent LVDP (L-asparaginase, etoposide, dexamethasone, cisplatin) regimen. All patients were staged by Ann Arbor staging system (AASS) and CA staging system (CASS). Their characteristics, treatment responses, survival outcomes, prognostic factors, and prognostic values of AASS and CASS were analyzed. The median follow-up time was 78 months. All patients received a median 4 cycles of the LVDP chemotherapy. Based on CASS, patients with stages I through IV were more evenly distributed than with AASS, and numbered at 56 (27.3%), 70 (33.2%), 45 (21.9%), and 34 (17.6%), respectively. At the end of therapy, the objective response rate (ORR) was 81.2% for all patients. For all patients, the 5-year progression-free survival (PFS) and overall survival (OS) were 61.6% and 67.8%. According to AASS, the 5-year OS of patients with stages Ⅰ through Ⅳ were 77.9%, 61.2%, 60.0%, and 38.7%, respectively (χ²=20.578, p<0.001). Based on CASS, the 5-year OS of patients with stages Ⅰ to Ⅳ were 89.1%, 65.5%, 58.6%, and 45.4%, respectively (χ²=22.973, p<0.001). In ROC analysis of OS, the area under the curve (AUC) for CASS was 0.70 and 0.64 for AASS. CASS was better in discriminating survival than AASS (p = 0.018). In conclusion, the LVDP regimen is effective for nasal-type ENKTL and the CASS has a better prognostic value in survival analysis than the AASS.     

Beclin 1 Deficiency Correlated with Lymph Node Metastasis,Predicts a Distinct Outcome in Intrahepatic and Extrahepatic Cholangiocarcinoma

Autophagy can be tumor suppressive as well as promotive in regulation of tumorigenesis and disease progression. Accordingly, the prognostic significance of autophagy key regulator Beclin 1 was varied among different tumors. Here, we detected the clinicopathological and prognostic effect of Beclin 1 in the subtypes of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Beclin 1 expression level was detected by immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that Beclin 1 was lowly expressed in 126 (70%) cholangiocarcinoma patients, consist of 72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node metastasis (N1) had a lower Beclin 1 level than that of N0 subgroup (P=0.012). However, we did not detect any correlations between Beclin 1 and other clinicopathological features, including tumor subtypes, vascular invasion, HBV infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis showed that, compared with the high expression subset, Beclin 1 low expression was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS 46.8%, P=041) for cholangiocarcinoma. Importantly, our stratified univariate and multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior PFS as well as overall survival than ECC, particularly than that of Beclin 1 highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low expression, correlated with lymph node metastasis, and might be a negative prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the anatomical location might lead to refined prognosis for the subtypes of ICC and ECC.     

Expression of the significance of silent information regulator type-1 in Angioimmunoblastic T-cell lymphoma is greater association with tumorigenesis and has strong implications for adverse prognosis

Silent information regulator type-1 (SIRT1) is the best-studied member of the Sirtuin (Sir2) family of nicotinamide dinucleotide (NAD)-dependent class III histone deacetylases (HDACs). Rrecently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma, but has not yet been explored in Angioimmunoblastic T-cell lymphoma (AITL). Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in AITL. Immunohistochemical expression of SIRT1, p53 were evaluated by using a 2 mm core from 45 AITL patients. Positive expression of SIRT1 was seen in 71.11% (32 of 45) of patients and p53 expression were seen in 53.33% (24 of 45). SIRT1 and p53 expression were significantly associated with shorter PFS by univariate analysis (P=0.009 and P < 0.001, respectively), multivariate analysis also shows that SIRT1 expression relate to worse prognosis. We also suggest inferior survival in AITL with the combined expression of SIRT1 and clinical characteristics of high IPI scores, high clinical stage, increased serum LDH, decreased HGB and increased γ-Globulin. In conclusion, our results indicate that SIRT1 is strongly expressed in AITL and it act as a clinically significant prognostic indicator for AITL patients, may also serve as a therapeutic target in AITL.     

CHOP-firstline treatment in NHL with unfavorable prognosis--evaluation of therapeutic response and factors influencing prognosis

58 NHL-patients (9 large cell centrocytic, 18 centroblastic, 16 immunoblastic, 15 lymphoblastic lymphomas) were treated immediately after diagnosis with CHOP-chemotherapy regardless of the extent of disease. Because of the advanced age of the majority of patients (median age 61 years, range 22-85 years) a reduced dose in the first two cycles was administered. Statistically significant prognostic variables influencing survival were the following: histologic subtypes according to the Kiel-classification (p less than 0,05), B-symptoms (p less than 0,001), blood sedimentation rate (p less than 0,02) and LDH (p less than 0,0005). With regard to prognosis there was no difference between patients over 60 years of age and younger ones (p less than 0,4). Patients achieving complete remission survived significantly longer (p less than 0,0001). Ann Arbor stages were of limited value, since patients with CS II disease and accumulation of risk factors (B-symptoms, abdominal disease, bulky tumor masses) showed a poorer outcome than patients with CS III who did not have these risk factors. A risk factor score summarizing features influencing prognosis is described and might be a useful tool in stratifying the heterogeneous group of NHL with unfavorable prognosis.     

Low expression of Beclin 1, associated with high Bcl-xL,predicts a malignant phenotype and poor prognosis of gastric cancer

Recent studies have suggested that dysregulation of autophagy plays a pivotal role in tumorigenesis. Here, we determined the prognostic value of autophagy-related protein Beclin 1 in gastric cancer. A total of 153 primary gastric cancer patients were subjected to analysis of Beclin 1 expression and survival prognosis. Among them, 68 patients were assigned randomly and used as a training set to generate a cutoff score for Beclin 1 expression by receive operating characteristic (ROC) curve analysis. The ROC-generated cutoff score was subjected to analyze the association of Beclin 1 with clinical characteristics and patient outcome. In a testing set (n = 85) and overall patients (n = 153), both univariate and multivariate analysis found that low expression of Beclin 1 predicted adverse overall survival and progression-free survival for gastric cancer patients. Furthermore, in each stage of gastric cancer patients, Beclin 1 expression was a prognostic indicator in patients with stage II, III and IV. Importantly, a reverse relationship between Beclin 1 and Bcl-xL expression was demonstrated. In patients of elevated Bcl-xL expression, a subset with lower Beclin 1 expression displayed an inferior overall survival and progression-free survival than those with higher Beclin 1 expression. Thus, our data demonstrated that low expression of Beclin 1, associated with high Bcl-xL, played as an independent biomarker, contributing to a more aggressive cancer cell phenotype and poor prognosis for gastric tumor.     

Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer

Recent studies have suggested that dysregulation of autophagy plays a pivotal role in tumorigenesis. Here, we determined the prognostic value of autophagy-related protein Beclin 1 in gastric cancer. A total of 153 primary gastric cancer patients were subjected to analysis of Beclin 1 expression and survival prognosis. Among them, 68 patients were assigned randomly and used as a training set to generate a cutoff score for Beclin 1 expression by receive operating characteristic (ROC) curve analysis. The ROC-generated cutoff score was subjected to analyze the association of Beclin 1 with clinical characteristics and patient outcome. In a testing set (n = 85) and overall patients (n = 153), both univariate and multivariate analysis found that low expression of Beclin 1 predicted adverse overall survival and progression-free survival for gastric cancer patients. Furthermore, in each stage of gastric cancer patients, Beclin 1 expression was a prognostic indicator in patients with stage II, III and IV. Importantly, a reverse relationship between Beclin 1 and Bcl-xL expression was demonstrated. In patients of elevated Bcl-xL expression, a subset with lower Beclin 1 expression displayed an inferior overall survival and progression-free survival than those with higher Beclin 1 expression. Thus, our data demonstrated that low expression of Beclin 1, associated with high Bcl-xL, played as an independent biomarker, contributing to a more aggressive cancer cell phenotype and poor prognosis for gastric tumor.     

Loss of FBXW7 is related to the susceptibility and poor prognosis of cervical squamous carcinoma

Objective: To investigate the relationship between F box/WD-40 domain protein 7 (FBXW7) and cervical squamous cancer.

Methods: We investigated the FBXW7 expression in 136 cervical squamous carcinoma cases through immunohistochemistry and Western-blot analysis to evaluate the clinical significance of FBXW7 and to elucidate the relationship of FBXW7 expression with progression-free survival (PFS) and overall survival (OS).

Results: Low FBXW7 expression was associated with high histologic grade, lymphovascular space invasion and lymph node metastasis, among other parameters. Patients with low FBXW7 expression exhibited poor OS and PFS.

Conclusions: FBXW7 is related to the susceptibility and prognosis of cervical squamous carcinoma, indicating FBXW7 may be a potentially important target for the prediction of prognosis.     

Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation,MGMT Promoter Methylation,and TERT Mutation Status: Experience from a Tertiary Care Center in India

This study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases. Combinatorial assessment of MGMT and TERT emerged as independent prognostic markers, especially in the IDH1 wild-type GBMs. Thus, within the IDH1 wild-type group, cases with only MGMT methylation (group 1) had the best outcome (median PFS: 83.3 weeks; OS: not reached), whereas GBMs with only TERT mutation (group 3) had the worst outcome (PFS: 19.7 weeks; OS: 32.8 weeks). Cases with both or none of these alterations (group 2) had intermediate prognosis (PFS: 47.6 weeks; OS: 89.2 weeks). Majority of the IDH1 mutant GBMs belonged to group 1 (75%), whereas only 18.7% and 6.2% showed group 2 and 3 signatures, respectively. Interestingly, none of the other genetic alterations were significantly associated with survival in IDH1 mutant or wild-type GBMs.Based on above findings, we recommend assessment of three markers, viz., IDH1, MGMT, and TERT, for GBM prognostication in routine practice. We show for the first time that IDH1 wild-type GBMs which constitute majority of the GBMs can be effectively stratified into three distinct prognostic subgroups based on MGMT and TERT status, irrespective of other genetic alterations.     

Concurrent Infection of Hepatitis B Virus Negatively Affects the Clinical Outcome and Prognosis of Patients with Non-Hodgkin’s Lymphoma after Chemotherapy

Hepatitis B virus (HBV) is hepatotropic and lymphotropic. HBV-infected individuals have an increased risk of developing malignant lymphoma, and the HBV infection rate in lymphoma patients is significantly higher than that in the general population. However, the exact mechanism and correlation between HBV infection and lymphoma onset and progression currently remain unclear. We retrospectively analyzed clinical data from non-Hodgkin’s lymphoma (NHL) patients with different HBV infection statuses. The results showed that the HBV infection rate was significantly higher in patients with B-cell type and late stage of NHL. The chemotherapy efficacy for NHL patients with chronic active HBV infection was significantly lower than that for the patients with chronic inactive HBV infection, the patients with HBV carriers and the patients without HBV infection. In addition, the NHL chemotherapy activated HBV replication and caused significant liver dysfunction, which could further reduce the chemotherapy efficacy. Through Kaplan-Meier survival curve and log-rank analysis, we found that the HBV infection status in NHL patients was significantly correlated with the patients’ progression-free survival (PFS) and overall survival (OS). Compared with the patients without HBV infection (PFS: 95% CI 47.915 to 55.640; OS: 95% CI 81.324 to 86.858), the PFS and OS of the patients with chronic active HBV infection were significantly shorter (PFS: 95% CI 9.424 to 42.589, P < 0.001; OS: 95% CI 42.840 to 82.259, P = 0.006). The study demonstrated that the sustained HBV replication in patients with chronic active HBV infection could be a key factor that influences the prognosis of NHL patients after chemotherapy, and thus may provide information for designing rational clinical treatments for NHL patients with different HBV infection statuses and improve the treatment efficacy and prognosis.     

Elevated IL-10 plasma levels correlate with poor prognosis in diffuse large B-cell lymphoma

The aim of the study was to confirm whether plasma levels of interleukin-10 (IL-10) correlate with the prognosis in diffuse, large B-cell lymphoma (DLBCL) patients. Plasma IL-10 levels were determined at the time of diagnosis in a group of 157 consecutively treated, DLBCL patients. Of those, 122 patients (78%) had IL-10 plasma levels below the detection limit (< 5 pg/mL) and 35 (22%) above this value. The median value for patients with detectable IL-10 levels was 35 pg/mL (range, 5 to 2480 pg/mL). Detectable plasma IL-10 levels were significantly associated with age > 60 years, ECOG performance status > or = 2, Ann Arbor advanced disease stage, bulky tumor mass, elevated serum levels of LDH and beta2-microglobulin, presence of anemia and low serum albumin levels as well as the presence of B symptoms. The patients with detectable IL-10 levels had lower probability of CR achievement (OR = 0.23, 95% CI 0.1-0.5, p = 0.0003). In addition, detectable IL-10 levels were significantly associated with shorter PFS (OR = 2.5, 95% CI 1.5-4.4, p = 0.001) and OS (OR = 3.0, 95% CI 1.7-5.2, p = 0.0001). In conclusion, we confirmed in this large group of DLBCL patients that elevated plasma IL-10 levels correlated with adverse disease features and poor prognosis. The plasma concentration of IL-10 may be a useful marker for evaluation of disease activity.     

外周血NETs、TP53、STAT3表达与弥漫性大B细胞淋巴瘤临床病理及预后的关系分析

摘要 目的：探究外周血中性粒细胞胞外诱捕网（NETs）、TP53、信号转导与转录因子3（STAT3）表达与弥漫性大B细胞淋巴瘤（DLBCL）临床病理及预后的关系。方法：选取2020年3月-2021年12月收治的71例DLBCL患者作为研究对象,抽取患者外周静脉血,采用R-CHOP方案进行治疗,记录患者外周血NETs、TP53、STAT3表达情况并分析DLBCL患者外周血NETs、TP53、STAT3表达与其临床病理及预后的关系。结果：髓细胞组织增生蛋白（MYC）阳性在TP53阳性中的占比显著高于TP53阴性,差异有统计学意义（x²=28.844,P＜0.001）;Hans分型生发中心B细胞（GCB）在STAT3阳性中的占比显著高于STAT3阴性（x²=4.331,P=0.037）,其余差异无统计学意义（P>0.05）;随访截止至2022年6月,随访时长8~28个月,71例患者中共53例缓解DLBCL患者,其余18例为R/R DLBCL患者;NETs阳性、TP53阳性、STAT3阳性患者无进展生存期（PFS）显著低于NETs阴性、TP53阴性、STAT3阴性患者,差异有统计学意义（P<0.05）且NETs阳性、TP53阳性、STAT3阳性患者存活率均低于NETs阴性、TP53阴性、STAT3阴性患者（P<0.05）;单因素分析结果显示Ann Arbor分期、NETs、TP53、STAT3为DLBCL患者的影响因素（P<0.05）;以患者预后情况（R/R DLBCL=1,缓解DLBCL=0）为因变量,将Ann Arbor分期、NETs、TP53、STAT3单因素分析有统计学意义的因素纳入COX回归模型中,结果显示：NETs、TP53、STAT3为DLBCL患者预后的危险因素（P<0.05）。结论：TP53、STAT3表达与DLBCL临床病理存在一定相关性,临床应对DLBCL患者TP53、STAT3表达情况引起重视;NETs、TP53、STAT3表达为DLBCL预后的危险因素,可作为DLBCL患者不良预后的预测指标。     

Serum Levels of Interleukin-9 Correlate with Negative Prognostic Factors in Extranodal NK/T-Cell Lymphoma

Interleukin-9 (IL-9) is more functionally diverse than previously expected, especially with regards to lymphomagenesis. However, the relationship between IL-9 and the clinicopathological features of extranodal NK/T-cell lymphoma is less well established. Patients with this lymphoma in Sun Yat-Sen University Cancer Center between January 2003 and March 2013 were systematically reviewed in an intention-to-treat analysis. Baseline serum IL-9 levels were determined using sandwich enzyme-linked immunosorbent assays. A total of seventy-four patients were enrolled in this study. The mean concentration of serum IL-9 for all patients was 6.48 pg/mL (range: 1.38–51.87 pg/mL). Age, B symptoms and local lymph node involvement were found to be related to high serum IL-9 levels. Patients with low IL-9 levels tended to have higher rates of complete remission. Notably, the median progression-free survival (PFS) and overall survival (OS) were longer in the low IL-9 level group than in the high IL-9 level group (PFS: 68.7 months vs. 28.3 months, P<0.001; OS: 86 months vs. 42.8 months, P = 0.001). Multivariate analysis revealed independent prognostic factors for PFS. Similarly, high IL-9 levels (P = 0.003) and old age (P = 0.007) were independently predictive of shorter OS. Serum IL-9 is closely related to several clinical features, such as age, B symptoms and local lymph node involvement. It can also be a significant independent prognostic factor for extranodal NK/T-cell lymphoma, which suggests a role for IL-9 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.     

乳腺恶性血液病的病理类型、临床特点及生存分析

目的:探讨乳腺恶性血液病的病理分型、患者的临床特征及预后。方法:回顾性分析2014年1月至2019年1月空军军医大学西京医院收治的33例乳腺恶性血液病患者的病理分型、临床特征及预后。结果:33例患者中,32例为女性,1例为男性,平均年龄为45.5岁(12-78岁)。经病理确诊29例(29/33,87.9%)为非霍奇金淋巴瘤,其中弥漫大B细胞淋巴瘤(18/29,62.1%)最为常见,其次是NK/T细胞淋巴瘤(3/29,10.3%),B淋巴母细胞白血病/淋巴瘤(2/29,6.8%),而伯基特淋巴瘤、滤泡淋巴瘤、原发皮肤间变大细胞淋巴瘤各1例(1/29,3.4%),其余3例未进一步分型。此外,1例(1/33,3.0%)霍奇金淋巴瘤,3例(3/33,9.1%)急性白血病复发累及乳腺。原发性乳腺恶性血液病为19例(57.6%),继发性为14例(42.4%),病变主要累及右侧乳腺(18例,54.5%),其次为左侧(10例,30.3%),双侧均累及的为少数(5例,15.2%)。19例原发性乳腺恶性血液病均为淋巴瘤,与14例继发性乳腺恶性血液病相比,其血小板计数明显升高(P=0.004),β2-MG显著降低(P=0.049),B症状少(P=0.017),Ann Arbor分期主要为Ⅰ-Ⅱ期(P<0.01),骨髓受累少(P<0.01)等特点。生存分析提示原发性乳腺恶性血液病患者比继发性患者生存期更长(HR=9.846,P=0.002)。恶性血液病累及骨髓可导致生存期显著缩短(HR=6.434,P<0.01)。结论:乳腺恶性血液病患者以中年女性为主,原发性乳腺恶性血液病比继发性发病率高(分别为57.5%和42.5%),最常见的病理类型为弥漫大B细胞淋巴瘤,病变主要累及右侧乳腺。与继发性乳腺恶性血液病相比,原发性乳腺恶性血液病患者具有血小板计数相对更高,β2-MG水平更低,往往不伴B症状,Ann Arbor分期主要为Ⅰ-Ⅱ期,骨髓不受累,且生存期显著延长等特点。此外,恶性血液病累及骨髓提示预后不良。