ZAP-70 Protein Retains Its Prognostic Significance within Interphase Cytogenetic Groups in B-Cell Chronic Lymphocytic Leukemia (B-CLL).

Abstract Heterogeneous clinical behavior of B-CLL makes difficult for physicians to identify which pts experience a slowly progressive clinical course and which ones may benefit from an early and/or more aggressive treatment. The development of interphase FISH techniques allowed to detect selected chromosome abnormalities in non-dividing cells. In 325 CLL pts, multivariate analysis identified 17p- and 11q- abnormalities as variables associated with shorter overall survival (OS) (Dohner, 2000). Moreover, the lack of IgVH gene mutation has been shown to predict a rapid disease progression (DP) and an inferior OS (Damle, Hamblin, 1999). B-CLL cells that use non-mutated IgVH genes express ZAP-70 protein, associated with an enhanced B cell receptor signaling and with an early DP risk. The aims of our study were: 1) to determine progression-free survival (PFS) and OS upon cytogenetic groups and ZAP-70 expression; 2) whether ZAP-70 could predict varied outcome within interphase cytogenetic groups; and 3) whether ZAP-70 and interphase cytogenetic groups were independent prognostic factors. We investigated 216 pts, median age 64 years, 69 pts belonging to low Rai stage, 140 to intermediate stage and 7 to high stage. To date, we have completed analysis of interphase cytogenetics in 137 pts, and ZAP-70 was quantified in 216 pts by a multicolor flow cytometric method using a cut-off value of 20%. With regard to cytogenetic groups, 73 (53.3%) pts had a normal karyotype and 35 (25.5%) pts had 13q-. Twenty-nine (21.2%) pts with trisomy 12, 17p- and 11q- were pooled together and defined as “poor-risk” cytogenetic subset. ZAP-70+ pts were 81/216 (37.5%) and there was a significant correlation between high or low ZAP-70 expression and Ig V gene mutational status (P<0.00001) in 125 examined CLL pts. Furthermore, we found significant associations either between higher ZAP-70 and trisomy 12, 17p-, 11q- or lower ZAP-70 and normal karyotype (P=0.0002). With regard to clinical outcome, a shorter PFS was observed in ZAP-70+ pts (13% vs 57% at 12 years; P<0.00001) and in “poor risk” cytogenetic pts vs normal karyotype pts (9% vs 49% at 12 years; P=0.008). The 13q- pts showed an intermediate outcome (23% at 12 years). ZAP-70+ pts showed also a shorter OS (24% vs 92% at 14 years; P=0.0002). To further explore the impact of ZAP-70 among cytogenetic groups, we investigated its expression within the normal karyotype and “poor risk” CLL subsets. As a matter of fact, ZAP-70 positivity was associated both with a shorter DFS and OS in normal karyotype (16% vs 62% at 10 years, P=0.002 and 69% vs 91% at 10 years, P=0.02, respectively) and in “poor risk” pts pooled together with 13q- pts (0% vs 35% at 13 years, P=0.0017 and 24% vs 100% at 14 years, P=0.03, respectively). In multivariate analysis of PFS, only ZAP-70 (hazard ratio=6.1, P=0.01) and soluble CD23 (hazard ratio=3.9, P=0.04) resulted to be independent prognostic factors. In conclusion, ZAP-70 expression predicts significantly both DFS and OS, and varies by interphase cytogenetic group. Within normal karyotype and poor risk cytogenetic subsets, where progression is heterogeneous, ZAP-70 positivity is able to distinguish pts who have early PFS or short OS. Therefore, ZAP-70 adds prognostic information to cytogenetic data and will assist in planning therapeutic decisions for CLL pts.

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Prognostic Value of Serum Soluble IL2 Receptor (sIL2R) Level in Patients with Diffuse Large B Cell Lymphoma (DLBCL), Treated with CHOP or R-CHOP Based Therapy.

Blood ◽

10.1182/blood.v110.11.1569.1569 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1569-1569

Author(s):

Yasuhiro Oki ◽

Keitaro Matsuo ◽

Harumi Kato ◽

Kazuhito Yamamoto ◽

Yoshitoyo Kagami ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

B Cell ◽

Cell Lymphoma ◽

Prognostic Significance ◽

B Cell Lymphoma ◽

Entire Group ◽

Extranodal Involvement ◽

The Impact

Abstract Emergence of rituximab (R) has significantly changed the clinical outcome of patients with B-cell lymphoma, which necessitates investigators to reassess the roles of previously determined prognostic factors. We performed a retrospective study to clarify the prognostic significance of serum sIL2R levels among other factors in patients with DLBCL. Study group consisted of 208 consecutive untreated patients with DLBCL who had serum sIL2R levels examined prior to treatment, and were treated in our institution between January 1999 and December 2006. Patients were treated with CHOP based chemotherapy without (R-, n=112) or with (R+, n=96) rituximab. Median follow up duration of each group was 55 and 19 months, respectively. Age (18–92), performance status (PS, ≥2 or <2), B symptoms (present or absent), stage (1–4), number of extranodal involvement (≥2 or <2), bulky diseases (largest diameter of the disease ≥ 10cm, present or absent) serum LDH levels and sIL2R levels were available in all patients. Beta-2 microglobulin levels were available in 130 patients. Serum sIL2R levels ranged from 316 to 35100 U/mL (median 1080), while standard range in healthy individuals was <520 U/mL. Spearman correlation analyses revealed that Log sIL2R level (LsIL2R) was associated with age (p<0.001), PS (p<0.001), B symptoms (p<0.001), stage (p<0.001), number of extranodal involvement ≥2 (p<0.001), Log LDH level (LLDH) (p<0.001) and beta2 microlobulin (p<0.001). The impact of each factor on overall survival (OS) was analyzed by Cox proportional Hazard model. Univariate analyses revealed that age (Hazard ratio [HR]=1.034, p=0.010), stage (HR=1.357, p=0.021), B symptoms (HR=1.152, p<0.001), R− (HR=2.123, p=0.049), PS (HR=4.102, p<0.001), number of extranodal involvement ≥2 (HR=2.592, p<0.001), LsIL2R (HR=3.249, p<0.001), LLDH (HR=4.378, p<0.001) and beta2 microglobulin (HR=1.283, p<0.001) were associated with shorter OS. When analyses was performed separately in R− and R+ groups, HR of LsIL2R was 3.59 (p<0.001) and 2.92 (p=0.071), respectively. Multivariate analysis in the entire group revealed that age (HR=1.030, p=0.041), PS (HR=2.089, p=0.038), B symptoms (HR=2.307, p=0.022), R− (HR=2.721, p=0.038), and LsIL2R (HR=2.140, p=0.018) were independently associated with shorter OS. When multivariate analysis was performed in R− group alone, age (HR=1.035, p=0.035), B symptoms (HR=3.565, p=0.001), and LsIL2R (HR=2.704, p=0.004) independently correlated with shorter OS. In the group of R+, only PS was left as an independent prognostic factor (HR=5.304, p<0.001). When LsIL2R was put back into the multivariate model of R+ group, HR of PS and LsIL2R became 4.308 (p=0.035) and 2.383 (p=0.165), respectively. In conclusion, serum sIL2R levels are frequently elevated in untreated patients with DLBCL and the higher level is significantly associated with shorter OS, independent of other known prognostic factors. When analysis was limited to R+ group, known prognostic factors such as age were not deemed independently associated with OS possibly due to short follow up duration and excellent prognosis in this population (estimated 3-year OS rate of 88%); thus longer follow up of this large cohort is necessary. Updated analyses for OS and various different analyses, such as analyses for correlation with complete response or time to treatment failure will be presented to further clarify the value of sIL2R levels.

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The Clinical Usefulness of Novel Prognostic Factors in CLL: A Study of 477 Patients with Low-Risk (Non-11q, Non-17p) FISH and Known IGVH Mutation Status.

Blood ◽

10.1182/blood.v110.11.3079.3079 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3079-3079 ◽

Cited By ~ 1

Author(s):

Constantine S. Tam ◽

Michael J. Keating ◽

Apostolia M. Tsimberidou ◽

Susan O’Brien ◽

Alessandra Tsimberidou ◽

...

Keyword(s):

Prognostic Factors ◽

High Risk ◽

Hazard Ratio ◽

Low Risk ◽

P Value ◽

Mutation Status ◽

Trisomy 12 ◽

The Impact ◽

Standard Risk ◽

Active Disease

Abstract In order to develop integrated models utilizing commonly available prognostic factors, we studied the clinical signficance of IGVH mutation, CD38 and ZAP-70 in 477 CLL patients (pts) with low-risk (non-11q, non-17p) FISH findings. All pts were untreated at the time of FISH assessment, and were collected prospectively in the MD Anderson CLL database. Two hundred & fifteen pts (45%) had mono- (n=160) or bi-alleleic (n=55) deletion of 13q {DEL13Q}, 162 pts (34%) had a negative FISH panel {NEG}, and 100 pts (21%) had trisomy 12 as sole FISH abnormality (n=78) or in association with deletion 13q (n=22) {T12}. Compared to other FISH groups, DEL13Q pts had lower B2m (median 2.2 v 2.6mg/L, p=0.01) and were less likely to be IGVH unmutated (33% v 48%, p=0.001). In contrast, T12 pts were more likely to present with advanced stage disease (Rai≥2 36% v 23%, p=0.01), be CD38 positive (44% v 13%, p<0.001), and have karyotypic abnormalities (48% v 7%, p<0.001). One hundred and twenty-three pts had active disease requiring immediate therapy and 354 pts had stable disease, of whom 291 were evaluable for disease progression. At a median follow-up of 20 months, 73 pts had developed active disease with NCI-WG indication(s) for treatment. Actuarial 2 year time to treatment (TTT) was 26%, with no significant difference between 13q, NEG and T12 pts (p=0.27). TTT was associated with elevated B2m (≥1.5ULN), IGVH mutation status and ZAP-70 in DEL13Q and NEG pts, but not in T12 patients (Table). For DEL13Q/NEG pts, a simple model using IGVH mutation and B2m separated high risk pts (unmutated or high B2m, 2yr TTT 43%) from standard risk pts (mutated and low B2m, 2yr TTT 11%, p<0.0001). For T12 pts, a model based on CD38 positivity and karyotypic abnormalities separated high risk pts (2 factors, 2yr TTT 75%) from standard risk pts (0 or 1 factor, 2yr TTT 15%, p=0.008). These results show that the impact of prognostic factors on TTT is dependent on the underlying FISH karyotype, and underscores the need for future studies in CLL prognostic factors to take into account the complete risk profile of the pt. NEGATIVE FISH DELETION 13Q TRISOMY 12 p-value hazard ratio p-value hazard ratio p-value hazard ratio IGVH Mutation <0.001 8.0 0.003 2.9 0.97 0.98 B2m ≥1.5ULN <0.001 4.5 0.07 2.2 0.54 0.68 CD38 Positivity 0.05 2.5 0.05 2.4 0.06 7.4 Abn Cytogenetics <0.001 11.0 0.27 2.2 0.09 2.8 ZAP-70 0.02 2.9 0.007 3.1 0.70 1.3 Figure Figure Figure Figure

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Impact of Immune Parameters on Long-Term Survival in Metastatic Renal Cell Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2005.03.9594 ◽

2006 ◽

Vol 24 (13) ◽

pp. 1997-2005 ◽

Cited By ~ 196

Author(s):

Frede Donskov ◽

Hans von der Maase

Keyword(s):

Risk Factors ◽

Renal Cell Carcinoma ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Renal Cell ◽

Prognostic Model ◽

Tumor Tissue ◽

Hazard Ratio ◽

Clinical Factors ◽

The Impact

Purpose The purpose of this study was to evaluate the impact of immunologic prognostic factors in combination with established clinical prognostic factors in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods A total of 120 consecutive patients with mRCC received interleukin-2 (IL-2) -based immunotherapy. Baseline tumor biopsies were available from 85 of these patients. Potential prognostic factors were analyzed by univariate and multivariate analyses. Results Multivariate analysis (N = 120) identified high lactate dehydrogenase, lymph node metastases, low hemoglobin, low Karnofsky performance status, and bone metastases as independent poor prognostic clinical factors. The impact of these clinical factors has been demonstrated by others. Multivariate analysis (n = 85) also identified a high blood neutrophil count (> 6.0 × 109/L; hazard ratio, 2.0; P = .015), the presence of intratumoral neutrophils (> 0 cells/mm2 tumor tissue; hazard ratio, 2.3; P = .001), and low intratumoral CD57+ natural killer cell count (< 50 cells/mm2 tumor tissue; hazard ratio, 2.1; P = .01) as independent poor prognostic immunologic factors. These three independent immunologic parameters had significant discriminatory power as supplemental risk factors in prognostic models based on the clinical risk factors, identifying subgroups within the favorable clinical group with estimated 5-year survival rates of 60%, 25%, and 0%, respectively. These findings were apparent in both our own prognostic model and in an extended Memorial Sloan-Kettering Cancer Center (New York, NY) prognostic model. Conclusion This study points on five clinical and three supplemental immunologic independent prognostic factors of survival in patients with mRCC receiving IL-2.

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Prognostic Significance of T-Cell or Cytotoxic Molecules Phenotype in Classical Hodgkin’s Lymphoma: A Clinicopathologic Study

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.5342 ◽

2006 ◽

Vol 24 (28) ◽

pp. 4626-4633 ◽

Cited By ~ 59

Author(s):

Naoko Asano ◽

Aya Oshiro ◽

Keitaro Matsuo ◽

Yoshitoyo Kagami ◽

Fumihiro Ishida ◽

...

Keyword(s):

Prognostic Factors ◽

T Cell ◽

B Cell ◽

Hodgkin’S Lymphoma ◽

Prognostic Significance ◽

Phenotypic Expression ◽

Hodgkin's Lymphoma ◽

Null Cell ◽

Poor Prognostic Factor ◽

Cytotoxic Molecules

Purpose Classical Hodgkin’s lymphoma (CHL) is characterized by Hodgkin’s and Reed-Sternberg (H-RS) cells, most of which are derived from germinal-center B cells. Nevertheless, one or more markers for T cells and follicular dendritic cells (FDC) may be expressed in a minority of H-RS cells in some CHL patients, although the clinical significance of this remains controversial. The aim of this study was to clarify the association between phenotypic expression and clinical outcome in CHL. Patients and Methods Participants were 324 consecutive CHL patients, comprising 132 patients with nodular sclerosis (NS), 35 patients with NS grade 2 (NS2), and 157 patients with mixed cellularity (MC). We evaluated the presenting features and prognosis of patients on categorization into four phenotypically defined groups: B-cell (CD20+ and/or CD79a+; n = 63), T-cell and/or cytotoxic molecules (CD3+, CD4+, CD8+, CD45RO+, TIA-1+, and/or granzyme B+; n = 27), FDC (CD21+ without B-cell marker; n = 22), and null-cell types (n = 212). Other potential prognostic factors were examined. Results The T-cell and/or cytotoxic molecules group showed a significantly poorer prognosis than the other three groups (P < .0001). This finding was seen consistently in multivariate analyses. Morphologic subtyping (NS/NS2/MC) and Epstein-Barr virus positivity were not identified as independent prognostic factors. Conclusion The presence of T-cell and/or cytotoxic antigens in H-RS cells may represent a poor prognostic factor in CHL, even if their expression is not regarded as lineage specific. Examination of T-cell and/or cytotoxic molecules phenotype in CHL patients is recommended as a routine pathologic practice.

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A high-resolution allelotype of B-cell chronic lymphocytic leukemia (B-CLL)

Blood ◽

10.1182/blood.v100.5.1787.h81702001787_1787_1794 ◽

2002 ◽

Vol 100 (5) ◽

pp. 1787-1794 ◽

Cited By ~ 28

Author(s):

Urban Novak ◽

Elisabeth Oppliger Leibundgut ◽

Jörg Hager ◽

Dominique Mühlematter ◽

Martine Jotterand ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Chromosomal Aberrations ◽

Cytogenetic Analysis ◽

Prognostic Significance ◽

Genetic Alterations ◽

Lymphocytic Leukemia ◽

Accurate Information ◽

Trisomy 12 ◽

Cell Chronic Lymphocytic Leukemia

The most frequent chromosomal aberrations in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q, 11q, and 17p, and trisomy 12, all of which are of prognostic significance. Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) are used for their detection, but cytogenetic analysis is hampered by the low mitotic index of B-CLL cells, and FISH depends on accurate information about candidate regions. We used a set of 400 highly informative microsatellite markers covering all chromosomal arms (allelotyping) and automated polymerase chain reaction (PCR) protocols to screen 46 patients with typical B-CLL for chromosomal aberrations. For validation, we compared data with our conventional karyotype results and fine mapping with conventional single-site PCR. All clonal cytogenetic abnormalities potentially detectable by our microsatellite PCR (eg, del13q14 and trisomy 12) were picked up. Allelotyping revealed additional complex aberrations in patients with both normal and abnormal B-CLL karyotypes. Aberrations detectable in the samples with our microsatellite panel were found on almost all chromosomal arms. We detected new aberrant loci in typical B-CLL, such as allelic losses on 1q, 9q, and 22q in up to 25% of our patients, and allelic imbalances mirroring chromosomal duplications, amplifications, or aneuploidies on 2q, 10p, and 22q in up to 27% of our patients. We conclude that allelotyping with our battery of informative microsatellites is suitable for molecular screening of B-CLL. The technique is well suited for analyses in clinical trials, it provides a comprehensive view of genetic alterations, and it may identify new loci with candidate genes relevant in the molecular biology of B-CLL.

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Clinicopathological Characteristics and Prognostic Factors in Axial Chondroblastomas: A Retrospective Analysis of 61 Cases and Comparison with Extra-Axial Chondroblastomas

10.21203/rs.3.rs-1242480/v1 ◽

2022 ◽

Author(s):

Bo-Wen Zheng ◽

Bo-Yv Zheng ◽

Hua-Qing Niu ◽

Xiao-Bin Wang ◽

Guo-Hua Lv ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Univariate Analysis ◽

Prognostic Significance ◽

Clinicopathological Characteristics ◽

Motor Dysfunction ◽

Surrounding Tissue ◽

Wide Resection ◽

Tissue Specimens

Abstract Background The clinical characteristics and prognostic factors of axial chondroblastoma (ACB) are still poorly understood. Purpose To characterize clinicopathological characteristics in a large ACB cohort and investigate their correlation with survival. We also sought to compare these results with extra-axial CB (EACB). Methods Our institution's local database was retrospectively reviewed and included a total of 132 CB patients, including 61 ACB patients and 71 EACB patients. Immunohistochemistry was used to assess the expression levels of Vimentin (Vim), S100, and cytokeratin (CK) on tumor cells in 132 tissue specimens. Results Overall, ACB and EACB had similar characteristics, except for older age and tumor size, as well as higher Vim expression, incidence of surrounding tissue invasion and postoperative sensory or motor dysfunction. Whereas wide resection and absence of invasion of surrounding tissues were consistently associated with favorable survival in the ACB and EACB cohorts in univariate analysis, most parameters showed differential prognostic significance between the 2 groups. Significant prognostic factors for local recurrence-free survival in multivariate analysis included the type of resection and chicken-wire calcification in the ACB cohort. Multivariate analysis of overall survival demonstrated that the type of resection was a significant predictor in the ACB cohort, whereas the type of resection and postoperative sensory or motor dysfunction were predictive of overall survival in the EACB group. Conclusion These data suggest that there may be distinct biological behaviors between ACB and EACB and may provide useful information to better understand the prognostic characteristics of patients with ACB and to improve outcome prediction in patients with ACB.

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Prognostic impact of serum cytokeratin 19 fragments in patient with metastatic urothelial cancer (mUC) treated with first-line chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.473 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 473-473

Author(s):

Yuki Endo ◽

Go Kimura ◽

Jun Akatsuka ◽

Masato Yanagi ◽

Hikaru Mikami ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Urothelial Cancer ◽

Cytokeratin 19 ◽

Intermediate Risk ◽

Line Treatment ◽

First Line ◽

Poor Risk ◽

Metastatic Urothelial Cancer ◽

First Line Treatment

473 Background: Even today, when several immune checkpoint Inhibitors have been approved for the treatment of metastatic urothelial cancer (mUC), cytotoxic chemotherapy (CTC) still remains the mainstay for first-line treatment. We believe that the prognostic factors for the first-line CTC have become more important again and need to be re-analyzed. Current guidelines do not yet provide recommendations for any serum tumor markers in patients with mUC. Previous studies have shown that serum cytokeratin 19 fragments levels (sCK) were correlated with depth of tumor invasion and metastatic burden in patients with bladder cancer. In this study we evaluated whether sCK, and other clinical parameters could predict overall survival (OS) in patients with mUC treated with CTC. Methods: Two hundreds fifty two patients with mUC received CTC from December 2006 to 2016 at our institution. sCK had been measured in 128 patients at diagnosis of mUC. OS rate were analyzed by Kaplan–Meier curves and log–rank test. Multivariate analysis was carried out using the Cox hazards model. Tumor burden (TB) was measured based on Response Evaluation Criteria In Solid Tumor (version 1.1). Results: Of 128 patients, with median age of 72 (44-93), 36 (28%) had lung metastasis, 11 (9%) had bone metastasis, 10 (8%) had liver metastasis (LM). Ninety five (74%) patients received platinum based chemotherapy as a first-line treatment. During the median follow-up period of 19 (1-89) months, 72 patients (70%) had died. A 1-year (1y) OS was 51% and a 2y-OS was 36%. On univariate analysis, performance status (PS) (HR2.0, p<0.005), sCK (HR3.9, p<0.001), CRP (HR4.0, p<0.001), neutrophil-lymphocyte ratio (HR1.9, p<0.049), LM (HR2.0, p=0.042) and TB (HR2.4, p<0.001) were the significant prognostic factors for OS. On multivariate analysis, PS (HR2.0, 95%CI (1.05-3.85) p=0.036 ), sCK (HR3.1, 95%CI (1.3-8.3), p=0.011), and LM (HR3.0, 95%CI (1.06-6.98), p=0.022) were the independent prognostic factors for OS. Based on these 3 factors we divided patients into three groups, good risk (G, 0 factor), intermediate risk (I, 1 factor) and poor risk (P, 2-3 factors). There was a significant difference between the three groups. (G vs I: p<0.001, I vs P: p=0.001). Conclusions: PS, sCK, and LM were the independent prognostic factors for OS in patients with mUC receiving CTC. For the patients in good or intermediate risk with this score, early exposure of ICIs should be performed after CTCs. Treatment strategy should be changed in patients with poor risk since CTC is primary refractory in such population.

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The Clinical and Prognostic Significance of Protein Arginine Deiminases 2 and 4 in Colorectal Cancer

Pathobiology ◽

10.1159/000518414 ◽

2021 ◽

pp. 1-11

Author(s):

Mohamed Gijon ◽

Rachael L. Metheringham ◽

Michael S. Toss ◽

Samantha J. Paston ◽

Lindy G. Durrant

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Survival Time ◽

Patient Survival ◽

Prognostic Significance ◽

High Expression ◽

Related Protein ◽

Post Translational Modification

Introduction: Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. Methods: PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. Results: CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (p = 0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with the expression of nuclear β catenin, PADI4, and alpha-enolase. In contrast, expression of nuclear PADI2 correlated with a decrease in survival (p = 0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (p = 0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of nuclear β catenin, alpha-enolase (p ≤ 0.0001, p = 0.002), and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (p = 0.011), with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase, and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2, and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC. Conclusion: High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.

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Osteopontin expression and its relationship with prognostic factors in diffuse large B-cell lymphoma

Hematology Reports ◽

10.4081/hr.2019.7964 ◽

2019 ◽

Vol 11 (3) ◽

Author(s):

Gilberto Barranco ◽

Edith Fernández ◽

Silvia Rivas ◽

Roxana Quezada ◽

Dolores Nava ◽

...

Keyword(s):

Prognostic Factors ◽

B Cell ◽

Germinal Center ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cox Proportional Hazards ◽

Biological Behavior ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

The aim of this study is to explore the expression of osteopontin (OPN) and its relationship with prognostic factors and survival in diffuse large B cell lymphoma (DLBCL). A tissue microarray was performed for immunohistochemical evaluation. Contingency tables were analyzed for trends; chi-square test was used to determine differences between groups. Univariate and multivariate Cox proportional hazards-regression analyses were performed to evaluate the impact of prognostic factors on survival. Expression of OPN was observed in 28%. It was different in non-germinal center DLBCL (P=0.04). The mean overall survival (OS) was lower in patients with positive OPN expression (19.762; CI 95% 14.269-25.255) it was not significant (P=0.123). It is not possible to establish a clear relationship between the expression by immunohistochemistry of osteopontin and a poor prognosis but it would be important to complement the analysis with other techniques as PCR or NGS that allow us to assess the influence of the isoforms and post-translational modifications of OPN on the biological behavior of DLBCL. Our findings indicate that OPN expression could be associated with a more aggressive variant of lymphoma: non-germinal center DLBCL.

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Prognostic Significance of Pretreatment Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio in Patients with Diffuse Large B-Cell Lymphoma

BioMed Research International ◽

10.1155/2018/9651254 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Siqian Wang ◽

Yongyong Ma ◽

Lan Sun ◽

Yifen Shi ◽

Songfu Jiang ◽

...

Keyword(s):

Prognostic Factors ◽

B Cell ◽

Cell Lymphoma ◽

Univariate Analysis ◽

Prognostic Significance ◽

B Cell Lymphoma ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Large B Cell Lymphoma ◽

Large B Cell

It is generally believed that there is correlation between cancer prognosis and pretreatment PLR and NLR. However, there are limited data about their role in diffuse large B cell lymphoma (DLBCL). This study aims to determine the prognostic value of pretreatment PLR and NLR for patients who have DLBCL. The associations between clinical characteristics and NLR and PLR were evaluated among 182 DLBCL patients from January 2005 to June 2016. The optimal cutoff values for high PLR (⩾150) and NLR (⩾2.32) in prognosis prediction were determined. The effect of NLR and PLR on survival was evaluated through multivariate Cox regression analysis, univariate analysis, and log-rank test. According to the evaluation results, patients with high NLR and PLR had significantly shorter OS (P=0.026 and P=0.035) and PFS (P=0.024 and P=0.022) compared with those who have low PLR and NLR. On multivariate analyses, IPI>2, elevated LDH, and PLR⩾2.32 were prognostic factors for OS and PFS in DLBCL patients. Therefore, we demonstrated that high PLR and NLR predicted adverse prognostic factors in DLBCL patients.

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