Prognostic Significance of High Ki-67 Index and Histogenetic Subclassification in Primary Central Nervous System Lymphoma

2018 ◽  
Vol 26 (4) ◽  
pp. 254-262 ◽  
Author(s):  
Uiju Cho ◽  
Woo Jin Oh ◽  
Yong-Kil Hong ◽  
Youn Soo Lee
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Significance ◽  
Central Nervous System Lymphoma ◽  
Ki 67

Prognostic Significance of Interim 11C-Methionine PET/CT in Primary Central Nervous System Lymphoma

2018 ◽  
Vol 43 (8) ◽  
pp. e259-e264 ◽  
Author(s):  
Seo-Yeon Ahn ◽  
Seong Young Kwon ◽  
Sung-Hoon Jung ◽  
Jae-Sook Ahn ◽  
Su Woong Yoo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Significance ◽  
Central Nervous System Lymphoma ◽  
Pet Ct

Hyperglycemia is Associated with Poor Survival in Primary Central Nervous System Lymphoma Patients

2016 ◽  
Vol 103 (3) ◽  
pp. 272-278 ◽  
Author(s):  
Ayumi Debata ◽  
Koichi Yoshida ◽  
Kenta Ujifuku ◽  
Haruna Yasui ◽  
Kensaku Kamada ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glucose Transporter ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Central Nervous System Lymphoma ◽  
Poor Performance Status ◽  
Poor Survival ◽  
Glut1 Expression

Purpose Primary central nervous system lymphoma (PCNSL) is a type of non-Hodgkin lymphoma (NHL), and it has been postulated that metabolic disorder may contribute to NHL etiology. We retrospectively investigated the prognostic significance of hyperglycemia in patients with PCNSL. We evaluated glucose transporter type 1 (GLUT1) expression by immunohistochemistry and analyzed its association with hyperglycemia and survival. Methods The medical and neuroradiologic records of 50 patients with PCNSL at our institution over the past 15 years were analyzed. Patients were divided into 3 groups based on mean fasting plasma glucose (FPG) levels: normal (<110 mg/dL), prediabetes (110-125 mg/dL), and diabetes (≥126 mg/dL). We defined prediabetes and diabetes groups as hyperglycemia. Results Forty-four percent of patients were in the prediabetes and diabetes groups. One-year survival rates were 73%, 66%, and 43% in normal, prediabetes, and diabetes groups, respectively. Univariate analysis revealed that high age, female sex, poor performance status, high mean FPG, and monotherapy were associated with shorter survival. Multivariable Cox regression analyses showed that high mean FPG and monotherapy were significant predictors of shorter survival (p = 0.036 and p = 0.000, respectively). The GLUT1 immunohistopathologic staining was performed in 34 cases, 20 of which (58%) showed variable levels of GLUT1 expression at the cell membrane and/or cytoplasm. Prediabetes and diabetes groups had a higher percentage of GLUT1-positive cells compared with the normal group (p = 0.015). Conclusions These findings indicate that hyperglycemia is associated with poor survival. The putative biological mechanism might involve differential GLUT1 expression between hyperglycemic and normal states in patients with PCNSL.

scholarly journals Whole Tumor Histogram Analysis Using DW MRI in Primary Central Nervous System Lymphoma Correlates with Tumor Biomarkers and Outcome

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1506 ◽  
Author(s):  
Chong ◽  
Ostrom ◽  
Khan ◽  
Dandachi ◽  
Garg ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Patient Outcomes ◽  
Central Nervous System Lymphoma ◽  
Cox Proportional Hazards ◽  
Tumor Segmentation ◽  
Tumor Proliferation ◽  
Ki 67 ◽  
Living With Hiv ◽  
Immunocompetent Patients

The ability to non-invasively predict outcomes and monitor treatment response in primary central nervous system lymphoma (PCNSL) is important as treatment regimens are constantly being trialed. The aim of this study was to assess the validity of using apparent diffusion coefficient (ADC) histogram values to predict Ki-67 expression, a tumor proliferation marker, and patient outcomes in PCNSL in both immunocompetent patients and patients living with HIV (PLWH). Qualitative PCNSL magnetic resonance imaging (MRI) characteristics from 93 patients (23 PLWH and 70 immunocompetent) were analyzed, and whole tumor segmentation was performed on the ADC maps. Quantitative histogram analyses of the segmentations were calculated. These measures were compared to PCNSL Ki-67 expression. Progression-free survival (PFS) and overall survival (OS) were analyzed via comparison to the International Primary Central Nervous System Lymphoma Collaboration Group Response Criteria. Associations between ADC measures and clinical outcomes were assessed using univariate and multivariate Cox proportional hazards models. Normalized ADC (nADC)Min, nADCMean, nADC1, nADC5, and nADC15 values were significantly associated with a poorer OS. nADCMax, nADCMean, nADC5, nADC15, nADC75, nADC95, nADC99 inversely correlated with Ki-67 expression. OS was also significantly associated with lesion hemorrhage. PFS was not significantly associated with ADC values but with lesion hemorrhage. ADC histogram values and related parameters can predict the degree of tumor proliferation and patient outcomes for primary central nervous system lymphoma patients and in both immunocompetent patients and patients living with HIV.

Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance

2009 ◽  
Vol 30 (3) ◽  
pp. 232-240 ◽  
Author(s):  
Delphine Raoux ◽  
Sébastien Duband ◽  
Fabien Forest ◽  
Béatrice Trombert ◽  
Marie-Laure Chambonnière ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Significance ◽  
Central Nervous System Lymphoma ◽  
Immunohistochemical Profile

scholarly journals Immunohistochemical Profile and Prognostic Significance in Chinese Primary Central Nervous System Lymphoma: Analysis of 132 Cases

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5026-5026
Author(s):  
Jing Liu ◽  
Yaming Wang ◽  
Xiaoyan Li ◽  
Zhe Liu ◽  
Xueyan Bai ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Significance ◽  
Central Nervous System Lymphoma ◽  
Ki67 Index ◽  
Resonance Imaging ◽  
Prognostic Variables ◽  
Kaplan Meier ◽  
Systemic Dlbcl

Abstract Primary central nervous system lymphoma (PCNSL) is aggressive and confined to the central nervous system, including the brain parenchyma, leptomeninges, spinal cord, eyes or cranial nervous. Morphologically, approximately 95% of these tumors are DLBCL according to the new World Health Organization (WHO) classification. However, PCNSL has treatment outcome distinct from those of systemic DLBCL, as well as dismal prognosis than systemic DLBCL. Our goal was to determine the immunohistochemical profile and prognostic significance for 132 Chinese PCNSL cases. The expression of CD20, CD10, BCL-6, MUM1, CD138, BCL-2, and Ki67 antigens were observed by immunohistochemical method. All cases expressed CD20. CD10, BCL-6, and MUM1 were positive in 15.2% (20/132), 86.4% (114/132), 90.2% (119/132). CD138 was negative in 100% (39/39). BCL-2 was positive in 89.3% (108/121). The Ki67 antigen, a proliferative index, ranging from 1% to 100% (median 85.3%) and 76.5% (101/132) PCNSLs showed Ki67 ≥ 90%. Among 132 cases, 25 (18.9%) were classified as germinal center B-cell-like (GCB); 107 (81.1%) were classified as activated B-cell-like (ABC). The Ki67 index in 25 GCB was similar to that in 107 ABC (p=0.663>0.05). No significant correlation was found between Ki67 index and BCL-2 (p=0.225>0.05). Significant positive correlation was found between Ki67 index and BCL-6 expression (p=.000<0.05). Among 132 cases, 43 had complete data of treatment that received chemotherapy regimens based on HD-MTX. GCB and ABC had similar OS (p=0.969) and PFS (p=0.070). These findings support that PCNSL predominantly express an ABC immunophenotype and express high Ki67 index, and suggest that the proliferative activity of GCB was similar to ABC and the expression of BCL-6 but not BCL-2 was positively correlated with the malignant degree of tumors. Table 1. Clinical characteristics. Characteristics Patients, n (%) Age (years); n=132 ≥60 y, n=53; <60 y, n=79 Median (range) 57 (21-85) Gender; n=132 Male 69 (52.3) Female 63 (47.7) ECOG; n=43 0-1 8 (18.6) 2-4 35 (81.4) LDH; n=43 Normal 25 (58.1) Elevated 18 (41.9) Numbers of lesions; n=132 1 48 (36.4) >2 84 (63.6) Involvement of deep structures; n=132 Absence 43 (32.6) Presence 89 (67.4) Table 2. Hans classification. CD10 BCL-6 MUM1 Immunoprofile PCNSL, n (%) + + + GCB 16 (12.1) + + - GCB 3 (2.3) + - + GCB 0 (0) + - - GCB 1 (0.7) - + - GCB 5 (3.8) - + + Non-GCB 90 (68.2) - - + Non-GCB 12 (9.1) - - - Non-GCB 5 (3.8) Table 3. Chang classification. CD10 BCL-6 MUM1 Immunoprofile PCNSL, n (%) + + - GCB (Pattern A) 3 (2.4) + - - GCB (Pattern A) 1 (0.8) - + - GCB (Pattern A) 5 (3.9) + + + activated GCB (Pattern B) 16 (12.6) + - + activated GCB (Pattern B) 0 (0) - + + activated GCB (Pattern B) 90 (70.9) - - + activated non-GCB (Pattern C) 12 (9.4) Figure 1. Immunohistochemical labeling. Figure 1. Immunohistochemical labeling. Figure 2. Kaplan-Meier curve shows clinical prognostic variables and their relationship to OS and/or PFS. Figure 2. Kaplan-Meier curve shows clinical prognostic variables and their relationship to OS and/or PFS. Figure 3. T1 axial, post-gadolinium magnetic resonance imaging of PCNSL. Figure 3. T1 axial, post-gadolinium magnetic resonance imaging of PCNSL. Disclosures No relevant conflicts of interest to declare.

scholarly journals PD-L1 and PD-L2 expression in the tumor microenvironment including peritumoral tissue in primary central nervous system lymphoma

2020 ◽  
Author(s):  
Motomasa Furuse ◽  
Hiroko Kuwabara ◽  
Naokado Ikeda ◽  
Yasuhiko Hattori ◽  
Tomotsugu Ichikawa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
Biological Factors ◽  
Peritumoral Tissue

Abstract Background: The prevalence of programmed death-ligand 1 (PD-L1) and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we analyzed needle biopsy and craniotomy specimens of patients with PCNSL to compare the PD-L1 and PD-L2 levels in the tumor and surrounding (peritumoral) tissue. We also assessed the correlation between biological factors and the prognostic significance of PD-L1 and PD-L2 expression. Methods: We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis. Results: The tumor cells expressed little or no PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95%CI: 0–94.6) than intratumoral macrophages (27.5%; 95%CI: 0–81.1, p=0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p=0.0429), with very low coefficient correlation (ρ=0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p=0.0008; better MSKCC score, p=0.0103; peritumoral macrophages: low proportion of LDH elevation, p=0.0064) and longer OS (for intratumoral macrophages: high PD-L1=60 months, 95%CI=30–132.6; low PD-L1=24 months, 95%CI=11–48; p=0.032; for peritumoral macrophages: high PD-L1=60 months, 95%CI=30.7–NR; low PD-L1=14 months, 95%CI=3–26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR=0.30, 95%CI=0.12–0.77, p=0.0129). Conclusions: Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL. Future comprehensive analysis of checkpoint molecules in the tumor microenvironment, including the peritumoral tissue, is warranted.

scholarly journals PD-L1 and PD-L2 expression in the tumor microenvironment including peritumoral tissue in primary central nervous system lymphoma

2019 ◽  
Author(s):  
Motomasa Furuse ◽  
Hiroko Kuwabara ◽  
Naokado Ikeda ◽  
Yasuhiko Hattori ◽  
Tomotsugu Ichikawa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Rank Test ◽  
Biological Factors ◽  
Peritumoral Tissue

Abstract Background: The prevalence of programmed death-ligand 1 (PD-L1) and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we analyzed needle biopsy and craniotomy specimens of patients with PCNSL to compare the PD-L1 and PD-L2 levels in the tumor and surrounding (peritumoral) tissue. We also assessed the correlation between biological factors and the prognostic significance of PD-L1 and PD-L2 expression. Methods: We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis. Results: The tumor cells expressed little or no PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95%CI: 0–94.6) than intratumoral macrophages (27.5%; 95%CI: 0–81.1, p=0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p=0.0429), with very low coefficient correlation (ρ=0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p=0.0008; better MSKCC score, p=0.0103; peritumoral macrophages: low proportion of LDH elevation, p=0.0064) and longer OS (for intratumoral macrophages: high PD-L1=60 months, 95%CI=30–132.6; low PD-L1=24 months, 95%CI=11–48; p=0.032; for peritumoral macrophages: high PD-L1=60 months, 95%CI=30.7–NR; low PD-L1=14 months, 95%CI=3–26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR=0.30, 95%CI=0.12–0.77, p=0.0129). Conclusions: Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL. Future comprehensive analysis of checkpoint molecules in the tumor microenvironment, including the peritumoral tissue, is warranted.

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