The prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma

The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among patients who did not receive upfront ASCT (n = 60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.     

Reactive perivascular T-cell infiltrate predicts survival in primary central nervous system B-cell lymphomas

Well-established histopathological prognostic factors are lacking in primary central nervous system (CNS) lymphomas (PCNSL). The present study investigated the presence and prognostic role of tumour necrosis (TN) and reactive perivascular T-cell infiltrate (RPVI), defined as a rim of small reactive T-lymphocytes occurring alone or located between the vascular wall and large neoplastic cells, in tumour samples from 100 immunocompetent patients with PCNSL. World Health Organization histotypes of the patients were: 96 diffuse large B-cell lymphomas, two Burkitt-like lymphomas, one anaplastic large T-cell lymphoma and one unclassified B-cell lymphoma. TN was observed in 24 (24%) cases and RPVI in 26 (36%) of 73 assessable cases. Patients with RPVI-positive lesions exhibited a significantly better overall survival (OS) than patients with RPVI-negative lymphoma, particularly among patients treated with high-dose methotrexate-based chemotherapy (3-year OS: 59 +/- 14% vs. 42 +/- 9%, P = 0.02). By contrast, the presence of TN did not demonstrate prognostic significance. Multivariate analysis confirmed an independent association between RPVI and survival. In conclusion, the presence of RPVI is independently associated with survival in PCNSL. This parameter can be easily and routinely assessed at diagnosis on histopathological specimens.     

Influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer

CONTEXT: The BRAF mutation may influence the expression patterns of molecular markers that are related to the development and progression of thyroid cancer. OBJECTIVE: The objective of the study was to investigate the effects of the BRAF V600E mutation on expression of galectin-3, cyclooxygenase-2, cyclin D1, p53, and vascular endothelial growth factor (VEGF) in papillary thyroid cancer (PTC). DESIGN, SETTING, AND SUBJECTS: One hundred sixty-three PTC and 28 nodular hyperplasia patients were selected retrospectively. The presence of the BRAF V600E mutation and the level of expression of the molecular markers were determined. RESULTS: Of 161 PTC patients, 102 patients (63.4%) were BRAF V600E(+), and these cases had significantly larger tumor sizes (P = 0.01), compared with V600E(-) cases (n = 59, 36.6%). Although PTC tissues had higher expression levels of the selected molecular markers than nodular hyperplasia tissues, expression levels of several molecular markers in BRAF V600E(+) PTC were not significantly different from those of BRAF V600E(-) PTC. But VEGF was significantly up-regulated in BRAF V600E(+) PTC, compared with BRAF V600E(-) PTC. VEGF expression levels were strongly positively correlated to tumor size (P < 0.001), extrathyroidal invasion (P = 0.02), and tumor stage (P = 0.04). Multivariate analysis clearly showed that VEGF expression was up-regulated in BRAF V600E(+) PTC (odds ratio 2.5, confidence interval 1.1-5.6; P = 0.03). CONCLUSIONS: BRAF V600E(+) PTC tended to have larger tumor volumes and higher expression of VEGF. The level of VEGF expression was closely correlated with tumor size, extrathyroidal invasion, and stage. The relatively high levels of VEGF expression may be related to poorer clinical outcomes and recurrences in BRAF V600E(+) PTC.     

半乳凝素3与慢性心力衰竭的相关性研究

目的 :探讨半乳凝素3(Gal-3)与慢性心力衰竭(CHF)患者心功能、前脑钠肽(pro-BNP)及高敏C反应蛋白(hs-CRP)等指标的相关性,以及Gal-3对CHF患者预后的预测作用。方法:选择CHF患者(CHF组)223例,健康体检者(对照组)61名。采用酶联免疫吸附法测定血清Gal-3、pro-BNP及hs-CRP水平,并进行血生化、肝功能、肾功能等检测。平均随访1年,将患者全因死亡、猝死作为终点事件。结果:CHF组Gal-3水平较正常对照组明显升高[(10.01±5.68)μg/L比(2.74±0.98)μg/L,P0.01],且lgGal-3与lg pro-BNP、lghs-CRP及心功能分级呈正相关(r=0.806,r=0.232,r=0.387,均P0.01),与左心室射血分数(LVEF)呈负相关(r=-0.137,P0.05)。多元回归分析表明pro-BNP、肌酐、纽约心脏病协会(NYHA)心功能分级及心房颤动病史是Gal-3水平的影响因素。Gal-3是CHF患者死亡的危险因素(P0.01)。结论:CHF患者血清Gal-3水平明显升高,与CHF严重程度(心功能分级)正相关,且Gal-3水平能为预测CHF患者预后提供参考价值。     

Trends in primary central nervous system lymphoma incidence and survival in the U.S.

It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)‐infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992–2011). HIV‐infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4158 PCNSLs were diagnosed (36% HIV‐infected; 0·9% transplant recipients). HIV prevalence in PCNSL cases declined from 64·1% (1992–1996) to 12·7% (2007–2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20–39 year‐old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (1·7% and 1·6%/year), but remained stable in other age groups. Five‐year survival was poor, particularly among HIV‐infected cases (9·0%). Among HIV‐uninfected cases, 5‐year survival increased from 19·1% (1992–1994) to 30·1% (2004–2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV‐infected and HIV‐uninfected PCNSL patients.     

A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases

Most primary central nervous system lymphomas (PCNSLs) in immunocompetent patients are diffuse large B-cell lymphomas (DLBCLs), characterized by poor prognosis, compared with systemic forms. A germinal center B-cell-like (GCB) origin of PCNSL was hypothesized on the basis of BCL-6 expression and ongoing mutational activity. Our goal herein was to determine, for 83 PCNSLs, the percentages of GCB and activated B-cell-like (ABC) phenotypes and their prognostic significance. CD10, BCL-6, MUM1, BCL-2, and CD138 antigens were immunohistochemically labeled on paraffin-embedded sections; the first 4 were positive in 2.4%, 55.5%, 92.6%, and 55.5% of the tumors, respectively. None of the 56 tested samples expressed CD138. Among the 82 patients with complete information, 79 (96.3%) were classified as ABC; 42 (51.2%) expressed BCL-6+ MUM1+, suggesting an "activated GCB" origin; 33 (40.2%) were exclusively MUM1+, and the remaining 4 (4.9%) were negative for all markers tested. These findings provide new insights into interpreting the poor PCNSL prognostic, which may, in part, be due to biologic aggressiveness associated with its activated B-cell-like pattern. We postulate assigning PCNSL a histogenetic "time-slot," overlapping late GC and early post-GC, that could explain the predominant ABC phenotype observed.     

Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer

AIM: To evaluate the expression of galectin-1 and vascular endothelial growth factor (VEGF) in gastric cancer and investigate their relationships with clinicopathologic factors and prognostic significance. METHODS: Galectin-1 and VEGF were immunohistochemically investigated in tumor samples obtained from 214 gastric cancer patients with all tumor stages. Immunohistochemical analyses for galectin-1 and VEGF expression were performed on formalin-fixed, paraffin-embedded sections of surgical specimens. The relationship between the expression and staining intensity of galectin-1 and VEGF, clinicopathologic variables, and patient survival were analyzed. All patients underwent follow-up until cancer-related death or more than five years after tumor resection. P values < 0.05 were considered statistically significant.RESULTS: Immunohistochemical staining demonstrated that 138 of 214 gastric cancer samples (64.5%) were positive for galectin-1, and 116 out of 214 gastric cancer samples (54.2%) were positive for VEGF. There was a significant association between galectin-1 and VEGF expression; VEGF was detected in 60.1% of galectin-1-positive samples and 43.4% of galectin-1-negative samples (P < 0.05). Galectin-1 expression was associated with tumor size, tumor location, stage, lymph node metastases, and VEGF expression (all P < 0.05). VEGF expression was related to tumor size, stage, and lymph node metastases (all P < 0.05). The 5-year survival rate was 56.6% for galectin-1-positive patients and 69.2% for galectin-1-negative patients, and the prognosis for galectin-1-positive patients was significantly poorer compared with galectin-1-negative patients (χ 2 = 13.880, P = 0.000). The 5-year survival rates for VEGF-positive and VEGF-negative patients were 53.4% and 70.5%, respectively (χ2 = 4.619, P = 0.032). The overall survival rate of patients with both galectin-1 and VEGF overexpression in gastric cancer tissue samples was significantly poorer than other groups (both P < 0.05).CONCLUSION: Galectin-1 expr     

The expressions and clinical significances of tissue and serum galectin-3 in pancreatic carcinoma

Purpose

Galectin-3, a member of the beta-galactoside-binding protein family, is involved in many biological processes, including cell proliferation, regulating cell cycle, angiogenesis, tumorigenesis, metastasis, etc. The aim of this study is to elucidate the relationship between galectin-3 and clinicopathological variables and to evaluate the clinical significance of serum galectin-3 in the diagnosis of pancreas carcinoma.

Methods

Galectin-3 expression in 78 pairs of pancreatic carcinoma tissues and the adjacent nontumorous tissues was tested by immunohistochemistry. The relationship between galectin-3 expression and clinical variables was analyzed. A sensitive method of time-resolved fluorescence immunological assay (TRFIA) for the detection of galectin-3 was established, and serum galectin-3 in cases with different pancreatic diseases was measured by TRFIA and ELISA. Further we compared the sensitivity and specificity of determining galectin-3, carcinoembryonic antigen (CEA) and carbohydrate antigen199 (CA199) for diagnosis of pancreatic carcinoma and assessed the complementary diagnostic value of galectin-3, CEA and CA199 for pancreatic carcinoma.

Results

Immunohistochemistry showed that galectin-3 expression was significantly higher in the human pancreatic carcinoma tissues than in the adjacent nontumorous tissues. The expression levels were correlated with the differentiation degree with the higher expression in poor differentiation tissues. Serum galectin-3 detected by both TRFIA and ELISA was much higher in patients with pancreatic carcinoma than in other groups. Serum galectin-3 was not correlated with CEA and CA199. Combined determination of these three markers has the complementary diagnostic value for human pancreatic carcinoma and may increase the diagnostic sensitivity to 97.5%.

Conclusions

Galectin-3 is overexpressed in pancreatic carcinoma tissues, and it is correlated with the tumor differentiation. Serum galectin-3 is higher in cases with pancreatic carcinoma than in benign pancreatic diseases and healthy persons. Combined determination of serum galectin-3, CEA and CA199 may improve the diagnostic power for pancreatic carcinoma.     

‘Prolymphocytoid’ Cells in Chronic Lymphocytic Leukaemia and their Prognostic Significance

The morphology of lymphocytes in blood and bone marrow smears from 103 patients with chronic lymphocytic leukaemia (CLL) was studied. Special attention was paid to the finding of immature cells with the morphological features of prolymphocytes (prolymphocytoid cells - PLC). Subsequently the prognostic significance of these cells was examined. It was found that in 85 cases no PLC were found (Group I); in 8 cases the percentage was ≤ 10% (Group II) and in 10 cases the PLC were > 10% (Group III). The cases with PLC, especially in group III, fell in advanced stages of the disease (III-IV) and presented with increased lymphocytosis. In 8 patients of group III, who were followed till death, the disease became refractory to any treatment and the survival was short. We suggest that ‘prolymphocytoid’ transformation is a bad prognostic sign in CLL.     

Increasing incidence of primary central nervous system lymphoma but no improvement in survival in Sweden 2000‐2013

Objectives

This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma (PCNSL) diagnosed 2000‐2013 in Sweden.

Methods

Cases were identified in the population‐based Swedish Lymphoma Register. Incidence per 100 000 person‐years and 95% confidence intervals (CI) were calculated, and PCNSL‐specific survival was estimated using relative survival. Tests for temporal trends were performed using Poisson regression. Population incidence of all brain tumors was retrieved for comparison.

Results

With 359 identified PCNSL cases (median age 66 years), overall incidence was 0.26 (95% CI: 0.24‐0.29) and the average annual increase 4% (P = .002). The increasing trend was primarily observed among elderly individuals (70+ years). Similarly, an increase in incidence of all brain tumors was noted only among the elderly. There was no significant improvement in relative survival across the study period although, among fit patients (with Eastern Cooperative Oncology Group, EGOC 0), survival plateaued 6 years after diagnosis.

Conclusion

The increasing PCNSL incidence in the elderly was consistent with an increasing incidence of brain tumors of any type and may in part be attributable to improved diagnostics and reporting in this group. New treatment options have not yet translated into general survival improvements in a population‐based setting, although the presence of long‐term survivors among fit patients is encouraging.     

Galectin-1 expression in prostate tumor-associated capillary endothelial cells is increased by prostate carcinoma cells and modulates heterotypic cell–cell adhesion

Besides providing tumors with nutrients, newly formed capillaries constitute a potential escape route for tumor cells favoring metastatic dissemination, and constitute an access for the anti-tumoral host immune cells. Galectin-1, a soluble human lectin, is involved in numerous biological functions including cell–cell and cell–substrate interactions. In addition, galectin-1 is able to induce apoptosis of activated T-lymphocytes. In this study, we have examined galectin-1 expression in capillaries associated to the carcinoma cells or present in the remote non-tumoral stroma of 100 human prostate carcinoma samples by immunoperoxidase staining. Galectin-1 was expressed by endothelial cells from capillaries infiltrating the tumor tissue in 64% (64/100) of the cases. On the contrary, endothelial cells in the adjacent non-tumoral stroma expressed galectin-1 in very few cases (7/100). Increased frequency of galectin-1-positive capillaries in the tumor-associated compared to the tumor-free areas was observed in 63% of the cases. This striking contrast led us to set up an in vitro model to test whether tumor cells could induce galectin-1 expression by endothelial cells. Incubation of human umbilical vein endothelial cells with conditioned media from PC-3 or DU 145 prostate carcinoma cells led to a significant increase of galectin-1 protein expression (+32.97% and 37.91% P < 0.01 and P < 0.05, respectively). PC-3 conditioned medium also induced increased adhesion values of PC-3 cells to the endothelial cells (53.4 ± 4.7 vs. 38.5 ± 3.5 after 30 min; 66.6 ± 7.8 vs. 46.2 ± 6.4 after 60 min). An anti-galectin-1 antiserum abolished this modulation, and recombinant galectin-1 also induced increased adhesion values in a dose-dependent fashion. This effect was specific as no such modulations were observed using normal lymphocytes instead of PC-3 cells. Preferential galectin-1 expression in the endothelial cells close to the cancer cells could provide these latter with increased abilities to interact with the endothelial cells as well as a defense against the host immune system. This revised version was published online in June 2006 with corrections to the Cover Date.     

Prognostic significance of calcium-binding protein S100A4 in colorectal cancer

BACKGROUND & AIMS: Prognostication in colon cancer almost exclusively still rests on the tumor stage. Furthermore, tumor-derived markers to improve discrimination of low- and high-risk subtypes generally are not in use. S100A4 has been reported to be associated with invasion and metastasis; however, no data are available on its prognostic value in colorectal carcinoma. Therefore, we investigated the prognostic significance of immunohistochemical S100A4 expression in colorectal carcinoma compared with clinicopathologic parameters and expression of cell-cycle markers p16, p21, p27, p53, Ki-67, and RB. METHODS: Archival tissue from 709 patients with colorectal cancer were retrieved, applied in tissue array technology, and investigated immunohistochemically. Univariate and multivariate survival analyses were carried out on all investigated parameters. RESULTS: Sixteen percent of cases showed high; 31%, low; and 53%, no S100A4 expression. In Kaplan-Meier analysis, S100A4 positively stained cases showed a significantly decreased survival time compared with negatively stained cases (P < 0.0001). In multivariate regression analysis, S100A4 expression emerged as a highly significant independent parameter (P < 0.001) with the highest relative-risk factor among other covariates. Nodal status (pN) lost its prognostic value if S100A4 was added to the model. High S100A4 expression was associated with tumor stage pT3/4, secondary metastasis, women, p16, and RB expression. CONCLUSIONS: S100A4 expression represents a highly significant prognostic marker in colorectal carcinoma, which is able to identify a subset of patients at high risk. In this respect, it is superior to established prognostic markers such as nodal status, pT stage, and p53 expression.     

High expression of TRAF4 in hepatocelullar carcinoma as an independent negative survival and recurrence predictor

Objective: To identify potential tumor markers for the development and recurrence of hepatocelullar carcinoma(HCC), this research studied the relationship between the expression of the tumor necrosis factor receptor-associated factor 4(TRAF4) and tumor angiogenesis together with its survival time of HCC patients. Methods: The expressions of TRAF4,vascular endothelial growth factor and CD34 were performed upon 90 patients with curative liver resection between August 2006 and November 2009 by immunohistochemical method in locally advanced HCC and adjacent non-tumoral liver. The expression of TRAF4 was determined by the Spearman rank correlation. Their prognostic factors on disease free survival(DFS) and overall survival(OS) were guaranteed by Kaplan-Meier and Cox regression analyses. The detection of the levels of vascular endothelial growth factor and CD34 was fulfilled in 90 cases of HCC. Results: TRAF4 expression was both significantly higher in HCC than in surrounding non-tumor tissues(57.8% vs. 22.2 %; P0.001) and significantly correlated with tumor size and tumor staging. High TRAF4 was correlated with reduced DFS rate(P=0.001) and overall OS rate(P0.001) and were displayed in Kaplan-Meier survival analysis. Conclusions: TRAF4 is involved with multifarious clinicopathologic features.TRAF4 expression, as an independent adverse prognostic factor, DFS and OS in HCC, is associated with increased tumor angiogenesis. The combined detection of TRAF4 in locally advanced HCC is a trustworthy predictive factor for the tumor development and recurrence.     

Aberrant methylation in the promoter region of the reduced folate carrier gene is a potential mechanism of resistance to methotrexate in primary central nervous system lymphomas

We investigated the prevalence and prognostic role of CpG island methylation of the reduced folate carrier (RFC) gene promoter region in primary central nervous system lymphoma (PCNSL) in immunocompetent patients. Genomic DNA from 40 PCNSL was used for methylation-specific polymerase chain reaction and bisulphite genomic sequencing of the RFC promoter region. Human immunodeficiency virus-negative systemic diffuse large B-cell lymphomas (DLBCL) were used as controls (n = 50). The impact on outcome of RFC promoter methylation was assessed in 37 PCNSL patients treated with high-dose methotrexate (HD-MTX)-based chemotherapy +/- radiotherapy. RFC promoter methylation occurred in 12 of 40 (30%) PCNSL and in four of 50 (8%) DLBCL (P = 0.01). Of 37 PCNSL treated with HD-MTX-based chemotherapy, methylation occurred in nine cases (24%, M-PCNSL), while 28 cases (76%, U-PCNSL) were negative. Three M-PCNSL (33%) and 15 U-PCNSL (54%) achieved complete remission (CR) after primary chemotherapy. Logistic regression confirmed the independent association between CR rate and International Extranodal Lymphoma Study Group score (P = 0.03), RFC promoter methylation (P = 0.07) and use of cytarabine (P = 0.08). The 3-year failure-free survival (FFS) and overall survival for M-PCNSL and U-PCNSL was 0% vs. 31 +/- 9% (P = 0.34) and 0% vs. 31 +/- 9% (P = 0.35) respectively. This is the first study to assess the methylation status of the RFC promoter in human tumour samples. RFC methylation is more common in PCNSL compared with systemic DLBCL, and is associated with a lower CR rate to HD-MTX-based chemotherapy. If confirmed in prospective trials on PCNSL treated with HD-MTX alone, these data may suggest the necessity for alternative strategies in M-PCNSL considering the increased risk of MTX resistance by tumour cells.     

Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia

The present study is the first to evaluate serum levels of vascular endothelial growth factor (VEGF) in B-cell chronic lymphocytic leukaemia (CLL). All 68 B-cell CLL patients and 31 control subjects analysed had detectable serum levels of VEGF, with no statistically significant difference between two proups. An aberrant increase of circulating levels of VEGF was found in only 17.6% of cases. B-cell CLL patients whose serum VEGF levels were higher than the median (i.e. 194.8 pg/ml) or 75th percentile (i.e. 288.5 pg/ml) values were more frequently at an advanced clinical stage. In contrast, no correlation with other clinico-biological features representative of either tumour mass [bone marrow (BM) histology, peripheral blood (PB) lymphocytosis, beta-2 microglobulin (beta-2m), LDH, interleukin-6 (IL-6)] or disease-progression (DP) [lymphocyte doubling time (LDT)] was found. Serum levels of VEGF predicted the risk of DP in early CLL. Among 41 patients in Binet stage A, progression-free survival (PFS) was significantly shorter in those patients whose VEGF serum concentrations were above the median value. Interestingly, characteristics of stage A patients stratified according to the median value of VEGF were similar with respect to many clinico-biological features, thus suggesting a possible independent prognostic role for such a marker. Finally, when added to the Rai subclassification, VEGF serum levels identified two groups with different PFS within stages I-II. We conclude that increased serum levels of VEGF can be considered useful for predicting the risk of DP and add prognostic information to the Rai subclassification of stage A CLL.     

Heparanase, galectin-3, and tissue factor mRNA are expressed in benign neoplasms of the thyroid

Objective: Heparanase, galectin-3, and tissue factor (TF) are overexpressed in solid malignant thyroid tumors. We studied their expression in multinodular goiters (MNGs). Design and Methods: Thyroid tissue specimens from 15 MNGs were obtained during surgery. mRNA expression for galectin-3, heparanase, and TF was assessed by RT-PCR. Results: Isolated expressions of heparanase and galectin-3 mRNA were expressed in 2 and 4 of the 15 MNGs, respectively; 8/15 MNGs were positive for both heparanase and galectin-3. TF mRNA was found in all MNG specimens. Conclusion: Galectin-3, heparanase, and TF RNA expression is prevalent in MNGs. Further studies will be needed to determine the prognostic significance of these findings.     

Serum Cyfra 21.1 and galectin-3 protein levels in relation to immunohistochemical cytokeratin 19 and galectin-3 expression in patients with thyroid tumors

Purpose  

The aim of this study was to assess the clinical utility of circulating preoperative Cyfra 21.1 [soluble fragment of cytokeratin (CK) 19] and galectin-3 (gal-3) in patients with thyroid tumors, to compare their serum values with tissue expression and to analyze the prognostic significance of these markers in relation to the clinical status of postsurgical differentiated thyroid carcinoma (DTC) patients.     

Cerebrospinal fluid soluble programmed death-ligand 1 is a useful prognostic biomarker in primary central nervous system lymphoma

The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD-L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD-L1 also exhibited superior overall discrimination performance compared to CSF sPD-L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD-L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep-brain involvement. Furthermore, CSF sPD-L1 could predict poor survival in PCNSL but CSF sPD-L2 could not. Intriguingly, CSF sPD-L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD-L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD-L1 blockade in PCNSL.