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The diagnosis of vitreoretinal lymphoma (VRL), a rare subtype of primary central nervous system lymphoma, is challenging. We aimed to investigate the mutational landscape of VRL by sequencing circulating tumor DNA (ctDNA) from aqueous humor (AH) and/or vitreous fluid (VF), as well as applying ctDNA sequencing to diagnosis and treatment monitoring. Baseline AH and/or VF specimens from 15 VRL patients underwent comprehensive genomic profiling using targeted next-generation sequencing. The molecular profiles of paired baseline AH and VF specimens were highly concordant, with comparable allele frequencies. However, the genetic alterations detected in cerebrospinal fluid ctDNA only partially overlapped with those from simultaneously collected AH/VF samples, with much lower allele frequencies. Serial post-treatment AH or VF samples were available for five patients and their changes in ctDNA allele frequency displayed a similar trend as the changes in interleukin-10 levels; an indicator of response to treatment. A cohort of 23 patients with primary central nervous system lymphoma was included as a comparison group for the genetic landscape and evaluations of the efficacy of ibrutinib. More MYD88 mutations, but fewer IRF4 mutations and CDKN2A/B copy number losses were observed in the baseline samples of primary central nervous system lymphoma than VRL patients. The objective response rate to ibrutinib treatment was much higher for patients with primary central nervous system lymphoma (64.7%, 11/17) than for those with VRL (14.3%, 1/7). In summary, we provide valuable clinical evidence that AH is a good source of tumor genomic information and can substitute VF. Moreover, molecular profiling of AH has clinical utility for the diagnosis of VRL and treatment monitoring.

In this post hoc subgroup analysis of 200 patients enrolled in China from the phase III PHOENIX trial ( N  = 838, NCT01855750), addition of ibrutinib to rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) did not improve event-free survival (EFS) versus placebo+R-CHOP in the intent-to-treat (ITT; n  = 200, hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0·509-1.349; p  = 0.4495) or activated B-cell-like (ABC; n  = 141 [based on available gene-expression profiling data], HR = 0.86, 95% CI: 0.467-1.570; p  = 0.6160) subpopulations. However, ibrutinib+R-CHOP improved EFS (HR = 0·50, 95% CI: 0.251-1.003) and progression-free survival (PFS; HR = 0.48, 95% CI: 0.228-1.009) versus placebo+R-CHOP in patients aged <60 but not ≥60 years. Grade ≥3 serious treatment-emergent adverse events occurred more with ibrutinib+R-CHOP (45·6% vs. 31·3%). The percentage of patients receiving ≥6 cycles of R-CHOP was similar across treatment arms in those <60 years. A numerical trend was seen towards improved EFS and PFS with ibrutinib+R-CHOP versus placebo+R-CHOP in patients with MYC -high/ BCL2 -high co-expression. In this slightly younger Chinese subgroup, ibrutinib+R-CHOP did not improve EFS in the ITT and ABC subpopulations but improved outcomes with manageable safety in patients <60 years, consistent with overall PHOENIX study outcomes., Competing Interests: S W, S M S, S S, Y Z, and J V: Janssen employment and stock ownership from Johnson and Johnson; B H, Z W, X W and Y F: Janssen employment; J Z, X H, Y S, S B, Q Z, Y S, H H, H Z and WW have no conflict of interest to disclose., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: T lymphoblastic lymphoma/leukemia (T-LBL/ALL) is an aggressive malignant tumor with 5-year overall survival (OS) rate reached 80% after high-dose chemotherapy. Due to the relatively low incidence of T-LBL/ALL, only a few risk factors have been identified. The occurrence and prognosis of malignant tumors are closely related to oxidative stress, but the prognostic relationship between T-LBL/ALL and systematic oxidative stress indexes has not been reported yet., Methods: A total of 258 T-LBL/ALL patients were retrospectively analyzed. The relationship between systematic oxidative stress indexes, such as creatinine (CRE), gamma-glutamyl transpeptidase ( γ -GGT), albumin (ALB), alkaline phosphatase (ALP), fibrinogen (FBG), C-reactive protein (CRP) and total bilirubin (TBIL), and survival of T-LBL/ALL patients, was analyzed. The weight of indexes was used to calculate the patients' oxidative stress risk score. The independent prognostic value of oxidative stress risk grouping (OSRG) was analyzed., Results: Higher CRE, CRP, and lower ALB were associated with poorer OS in T-LBL/ALL patients. The OSRG established by CRE, ALB, and CRP was an independent prognostic factor for OS of T-LBL/ALL patients. Patients in the high-risk group were more likely to be patients older than 14 years old and patients with superior vena cava obstruction syndrome (SVCS), pleural effusion, pericardial effusion, and mediastinal mass., Conclusion: For OS in T-LBL/ALL patients, OSRG was observed as an independent prognostic factor, which provided a new idea for accurate prognostic prediction., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2022 Liqin Ping et al.)

Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas. We previously showed that 20% of diffuse large B-cell lymphoma (DLBCL) patients from China, an endemic area of HBV infection, have chronic HBV infection (surface antigen-positive, HBsAg+) and are characterized by distinct clinical and genetic features. Here, we showed that 24% of follicular lymphoma (FL) Chinese patients are HBsAg+. Compared with the HBsAg- FL patients, HBsAg+ patients are younger, have a higher histological grade at diagnosis, and have a higher incidence of disease progression within 24 months. Moreover, by sequencing the genomes of 109 FL tumors, we observed enhanced mutagenesis and distinct genetic profile in HBsAg+ FLs, with a unique set of preferentially mutated genes (TNFAIP3, FAS, HIST1H1C, KLF2, TP53, PIM1, TMSB4X, DUSP2, TAGAP, LYN, and SETD2) but lack of the hallmark of HBsAg- FLs (ie, IGH/BCL2 translocations and CREBBP mutations). Transcriptomic analyses further showed that HBsAg+ FLs displayed gene-expression signatures resembling the activated B-cell-like subtype of diffuse large B-cell lymphoma, involving IRF4-targeted genes and NF-κB/MYD88 signaling pathways. Finally, we identified an increased infiltration of CD8+ memory T cells, CD4+ Th1 cells, and M1 macrophages and higher T-cell exhaustion gene signature in HBsAg+ FL samples. Taken together, we present new genetic/epigenetic evidence that links chronic HBV infection to B-cell lymphomagenesis, and HBV-associated FL is likely to have a distinct cell-of-origin and represent as a separate subtype of FL. Targetable genetic/epigenetic alterations identified in tumors and their associated tumor microenvironment may provide potential novel therapeutic approaches for this subgroup of patients., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Cell therapies have progressed to cures for hematopoietic disorders, neurodegenerative diseases, and cancer. However, only some patients can benefit from cell therapies even with prior screening. Due to the limited clinical methods to monitor the in vivo therapeutic functions of these transferred cells over time, the uncertain prognosis is hard to attenuate. Positron emission tomography (PET) cell tracking can provide comprehensive dynamic and spatial information on the proliferation status and whole-body distribution of the therapeutic cell. In this work, we designed and synthesized the first SNAP-tagged PET radiotracer. SNAP tag is an O 6 -alkylguanine-DNA alkyltransferase that can form an irreversible bond with 18 F-BG-surface for in vivo cell tracking based on a reporter gene system. 18 F-BG-surface was obtained by the F-Al radiolabeling method in 32 ± 7% radiochemical yield and showed a high in vitro stability in mouse serum. SNAP-tagged cells could be selectively targeted by 18 F-BG-surface both in vitro (4.81 ± 0.08%AD/10 6 cell vs 2.26 ± 0.10%AD/10 6 cell) and in vivo (1.90 ± 0.05 vs 0.55 ± 0.02% ID/g, p < 0.01)., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Peripheral T-cell lymphoma (PTCL) is featured with a poor survival outcome. China has approved chidamide, an oral novel histone deacetylase inhibitor, for patients diagnosed with relapsed or refractory PTCL., Objective: We compared the benefit of traditional chemotherapy alone and a combination of chidamide and traditional chemotherapy against newly diagnosed PTCL. Prognostic factors related to progression and survival in patients diagnosed with untreated PTCL were also investigated., Methods: 104 patients with newly diagnosed PTCL were enrolled and divided into chemotherapy (ChT) group and chemotherapy combined with chidamide (ChT+C) group. Survival curves were plotted by the Kaplan-Meier method. Univariate and multivariate analysis were conducted with Log-rank test and Cox's proportional hazard regression. Subgroup analysis and interaction tests were conducted to evaluate factors associated with prognostic differences between ChT and ChT+C groups., Results: Compared with patients in ChT group, those in ChT+C group had superior progression-free survival (PFS) ( p =0.047). However, there was no significantly statistical difference observed between the two groups in overall survival (OS) ( p =0.212). High IPI scores have a negative relationship with survival. Multivariate analysis revealed that the type of frontline treatment regimen is an independent factor associated with PFS of PTCL patients ( p =0.045). In the subgroup of patients with high international prognostic index scores (3-5), the HR value for PFS comparing ChT with ChT+C was 4.675. A test of interaction between IPI and treatment showed statistical significance ( p = 0.037), implying that the benefits of ChT+C are higher for patients with high IPI scores., Conclusions: In summary, the combination of ChT and chidamide may provide a promising prospect for patients with newly diagnosed PTCL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with the authors NS, SM, XT, HuH, and QC., (Copyright © 2022 Wang, Su, Fang, Ma, Zhang, Cai, Zou, Tian, Xia, Liu, Li, Huang, Huang and Cai.)

Purpose: The aim of the study was to delineate the disease characteristics, the initial treatment patterns, and survival in patients with mantle cell lymphoma (MCL) managed in the real world., Methods: Data of 518 MCL patients from 5 major Chinese Hematology Centers in the period from 2007 to 2017 were retrospectively analyzed., Results: The median age was 58 years. Of the patients, 88.6% had Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 and 80.7% had advanced-stage disease. Ki67 expression was <30% in 39.6% of the patients, and 43.2% of patients were categorized into a low-risk group based on the Mantle Cell Lymphoma International Prognostic Index (MIPI) scoring system. Overall, 73.4% of the patients received rituximab as their first-line therapy. The most commonly used chemotherapy was the CHOP-like (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) regimen (45.2%), followed by high-dose cytarabine-containing chemotherapy (31.3%) and bendamustine (3.3%). Of the patients, 13.7% ( n  = 71) underwent consolidative autologous stem cell transplantation (ASCT), and 19.3% ( n  = 100) received novel agents containing first-line regimens. With a median follow-up time of 52 months, the 3- and 5-year overall survival (OS) rates were 73.7% and 61.4%, respectively. Age ≤60 years, ECOG PS 0-1, stages I-II, normal lactate dehydrogenase (LDH), absence of bone marrow involvement, Ki67 <30%, and lower-risk IPI/MIPI scores were significantly associated with improved OS ( p  < 0.05). The inclusion of rituximab improved the 5-year OS, with borderline significance (62.5% vs . 55.2%, p  = 0.076). High-dose cytarabine-containing chemotherapy showed significant clinical benefit in 5-year OS (72.1% vs . 55.9%, p  = 0.010). Patients with ASCT had better 5-year OS in the younger (≤60 years) age group (87.2% vs . 64.8%, p  = 0.002)., Conclusion: This large retrospective dataset unequivocally confirmed the survival advantage afforded by cytarabine-containing regimen and ASCT in a first-line setting under real-world management in the rituximab era., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Li, Huang, Xu, Wang, Huang, Zhao, Liu, Xu, Chen, Zhu, Song, Ruan and Wu.)

Background: Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL., Methods: This phase 2 study with Simon's two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification)., Results: In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5-43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29-339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43-106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94-438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab., Conclusions: In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016.

Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m 2 (day 1), gemcitabine 1 g/m 2 (days 1 and 8) and oxaliplatin 130 mg/m 2 (day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using 18 F-fluorodeoxyglucose positron emission tomography ( 18 FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy. Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D, TET2, and BCORL1 might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.

Background: Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL., Objective: As the distribution of PTCL subtypes differs between populations and few patients in the pivotal trial of pralatrexate were Asian, this study investigated the safety and efficacy of pralatrexate as monotherapy in Chinese patients with R/R PTCL., Patients and Methods: In this single-arm, open-label, multicenter study, 71 patients with R/R PTCL (median [range] 2 [1-14] prior systemic treatments) were recruited from 15 centers in China and received pralatrexate IV 30 mg/m 2 /week for 6 weeks in 7-week cycles (with vitamin B 12 /folate). The primary endpoint was objective response rate (ORR) per central review (null hypothesis: ORR < 15%)., Results: The study's primary objective was met: ORR (95% CI) was 52% (40-64%) (p < 0.001) and responses were observed across pre-specified patient subgroups. Median (95% CI) duration of response was 8.7 (3.3-14.1) months and first response was observed in Cycle 1 for most (84%) patients. Median (95% CI) progression-free survival and overall survival was 4.8 (3.1-8.1) months and 18.0 (10.4-NA) months, respectively. The most common treatment-emergent adverse events were stomatitis (68% [Grade 3/4: 20%]), anemia (49% [Grade 3/4: 24%]) and alanine aminotransferase increase (41% [Grade 3/4: 4%])., Conclusions: These results demonstrate that pralatrexate may represent a promising treatment option for Chinese patients with R/R PTCL. The ORR of 52% compared favorably with prior studies of pralatrexate in other populations and there were no unanticipated side effects., Trial Registration: ClinicalTrials.gov identifier: NCT03349333.

The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m 2 /cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m 2 /cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

Hepatitis B virus (HBV) infection is endemic in some parts of Asia, Africa, and South America and remains to be a significant public health problem in these areas. It is known as a leading risk factor for the development of hepatocellular carcinoma, but epidemiological studies have also shown that the infection may increase the incidence of several types of B-cell lymphoma. Here, by characterizing altogether 275 Chinese diffuse large B-cell lymphoma (DLBCL) patients, we showed that patients with concomitant HBV infection (surface antigen positive [HBsAg + ]) are characterized by a younger age, a more advanced disease stage at diagnosis, and reduced overall survival. Furthermore, by whole-genome/exome sequencing of 96 tumors and the respective peripheral blood samples and targeted sequencing of 179 tumors from these patients, we observed an enhanced rate of mutagenesis and a distinct set of mutation targets in HBsAg + DLBCL genomes, which could be partially explained by the activities of APOBEC and activation-induced cytidine deaminase. By transcriptome analysis, we further showed that the HBV-associated gene expression signature is contributed by the enrichment of genes regulated by BCL6, FOXO1, and ZFP36L1. Finally, by analysis of immunoglobulin heavy chain gene sequences, we showed that an antigen-independent mechanism, rather than a chronic antigenic simulation model, is favored in HBV-related lymphomagenesis. Taken together, we present the first comprehensive genomic and transcriptomic study that suggests a link between HBV infection and B-cell malignancy. The genetic alterations identified in this study may also provide opportunities for development of novel therapeutic strategies., (© 2018 by The American Society of Hematology.)

Hemophagocytic syndrome (HPS) is a fatal hyperinflammatory disease with a poorly understood mechanism that occurs most frequently in extranodal natural killer/T cell lymphoma (ENKTL). Through exome sequencing of ENKTL tumor-normal samples, we have identified a hotspot mutation (c.419T>C) in the evolutionarily conserved signaling intermediate in Toll pathway (ECSIT) gene, encoding a V140A variant of ECSIT. ECSIT-V140A activated NF-κB more potently than the wild-type protein owing to its increased affinity for the S100A8 and S100A9 heterodimer, which promotes NADPH oxidase activity. ECSIT-T419C knock-in mice showed higher peritoneal NADPH oxidase activity than mice with wild-type ECSIT in response to LPS. ECSIT-T419C-transfected ENKTL cell lines produced tumor necrosis factor (TNF)-α and interferon (IFN)-γ, which induced macrophage activation and massive cytokine secretion in cell culture and mouse xenografts. In individuals with ENKTL, ECSIT-V140A was associated with activation of NF-κB, higher HPS incidence, and poor prognosis. The immunosuppressive drug thalidomide prevented NF-κB from binding to the promoters of its target genes (including TNF and IFNG), and combination treatment with thalidomide and dexamethasone extended survival of mice engrafted with ECSIT-T419C-transfected ENKTL cells. We added thalidomide to the conventional dexamethasone-containing therapy regimen for two patients with HPS who expressed ECSIT-V140A, and we observed reversal of their HPS and disease-free survival for longer than 3 years. These findings provide mechanistic insights and a potential therapeutic strategy for ENKTL-associated HPS.

There are currently no prognostic biomarkers for extranodal natural killer/T-cell lymphoma (ENKTL) patients receiving asparaginase-based chemotherapy. Interleukin-10 (IL-10) is a pleiotropic cytokine that is involved in the stimulation and suppression of immune responses and influences the prognosis of different subtypes of lymphoma. We retrospectively analyzed 98 newly diagnosed patients with ENKTL receiving asparaginase-based chemotherapy. Baseline serum IL-10 levels were tested with sandwich enzyme-linked immunosorbent assays. Patients with high IL-10 (≥12.28 pg/mL) at diagnosis tended to have more adverse clinical features. Patients with low IL-10 (<12.28 pg/mL) at diagnosis had better progression-free survival (PFS) (P>0.001) and overall survival (OS) (P<0.001). Multivariate analysis revealed that baseline serum IL-10 level ≥12.28 pg/mL, stage III/IV, elevated serum ferritin, and elevated serum Epstein-Barr virus DNA level at diagnosis were four adverse factors for PFS and OS. Based on these four independent prediction factors, we divided the patients into different subgroups as follows: group 1, no adverse factors; group 2, one factor; group 3, two factors; and group 4, three or four factors. Furthermore, significant differences in PFS and OS were found between the groups. Our results suggest that pretreatment serum IL-10 is a novel, powerful predictor of prognosis for ENKTL patients receiving asparaginase-based chemotherapy, which suggests a role for IL-10 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.

Objective: To investigate the flavonoids in Rhododendron mariae., Method: The constituents in R. mariae were determined by UPLC/Q-TOF-MS. The chromatographic separation was performed on a C18 column (2.1 mm x 50 mm, 1.7 microm) with a gradient elufion of methanol-water containing 0.1% formic acid. The mass specfrometer eqaipped with elecfrospay ionizafion source was usedas defecfor and operated in data was collected under the positive and negative ion modes., Result: Seven constituents were identified as myricetin-3-O-beta-D-gluconside (1), myricetin-3'-O-beta-D-xylopyraoside (2), hyperoside (3), isoquercitrin (4), avicularin (5), quercitroside (6) and quercetin (7)., Conclusion: In this study, the main flavonoids in R. mariae were separated by UPLC, and identified through the information of positive ion and negative ion and relative molecular mass which were determined by Q-TOF-MS. It is an accurate and effective method which can be applied for the constituent identification of R. mariae.

Background: To study the expressions and its clinical significances of fas and P53 protein in human non-small cell lung cancer (NSCLC) after complete surgical resection., Methods: Immunohistochemical stain of fas and P53 was performed on paraffin-embedded sections from 269 NSCLC patients who underwent surgery and were followed up for 1.1 to 122.2 (median, 48.4) months postoperatively. Differences in survival rates and clinical characteristics were evaluated by SPSS10.0 statistical software packet., Results: The rate of fas and P53 expression in NSCLC cancer tissue was 43.1% and 49.4% respectively. Fas expressions were seen more frequently in female patients (59.3% vs 39.1%, P < 0.01). Univariate analysis showed that fas expression was a good factor for predicting prognosis. The 5-year survival rate of the patients whose tumors had positive fas expression was significantly better than those individuals whose tumors had negative fas expression (51.4% vs 42.4%, P=0.02), especially in patients in stage I and IIIA . The expression of P53 had no significant influence on the prognosis of these 269 NSCLC patients. Combined analysis of fas and P53 expression in NSCLC cancer tissues showed significant prognostic influence (P=0.01). The 5-year survival were 40.1% (fas+ and P53-), 45.4% (both positive or both negative) and 57.2% (fas- and P53+), respectively. COX multivariate analysis showed that reduced fas expression in 269 NSCLC is an independent risk factor, especially in stage IIIA NSCLC., Conclusions: Fas and P53 protein are indicators of NSCLC biological behavior. Reduced fas expression in NSCLC is an independent risk factor for early stage patients. Analysis of apoptosis related proteins expression in tumors might be helpful to predict the prognosis of patients with NSCLC.