scholarly journals Immunohistochemical Evaluation and Prognostic Value of Monocarboxylate Transporter 1 (MCT1) and 4 (MCT4) in T-cell Non-Hodgkin Lymphoma

2021 ◽  
Author(s):  
Hu Zhao ◽  
Yuan Chen ◽  
You-Ping Liao ◽  
Hai-Mei Chen ◽  
Qiu-Hong Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Value ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Monocarboxylate Transporter ◽  
Disease Stage ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
Monocarboxylate Transporter 1

Abstract Tumor cells often exhibit the Warburg effect, wherein, they preferentially undergo glycolysis over oxidative phosphorylation for energy production. Monocarboxylate transporter 1 (MCT1) and 4 (MCT4) are critical symporters mediating lactate efflux and preventing intracellular acidification during tumor growth. Numerous studies have focused on inhibiting MCT1 or MCT4 in various cancers. However, its role in T-cell lymphoma (TCL) is not yet investigated owing to the low incidence of TCL. This study was designed to investigate the expression of MCT1/MCT4 in patients with TCL and determine their prognostic value in this cancer. We performed immunohistochemistry to evaluate the expression level of MCT1/MCT4 in 38 TCL tissue samples and then compared their expression among different TCL subgroups, which were formed based on different clinical characteristics. Survival analysis was performed to evaluate the relationship between MCT1/MCT4 expression and both overall survival (OS) and progression-free survival (PFS). Our results revealed that MCT1 and MCT4 expression was significantly increased in TCL tissues compared to the control group. In addition, increased MCT1 expression associated with the female sex, advanced disease stage, increased serum LDH, Ki-67 at ≥50%, and intermediate or high-risk groups as categorized by the International Prognostic Index (IPI) score. We also found that increased MCT1 expression may be associated with reduced OS and PFS. In conclusion, MCT1 and MCT4 are overexpressed in patients with TCL, and may predict poor prognosis. MCT1 inhibition might be a novel treatment strategy for TCL, and further preclinical trials are required.

scholarly journals Cepp in Previously Untreated Patients with Mature T Cell Lymphomas

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1371-1371
Author(s):  
Hian Li Esther Chan ◽  
Joanne Lee ◽  
Sanjay De Mel ◽  
Anand Devaprasath D. Jeyasekharan ◽  
Yen Lin Chee ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Clinical Stage ◽  
International Prognostic Index ◽  
Autologous Transplantation ◽  
Prognostic Index ◽  
Disease Stage ◽  
Control Group ◽  
Curative Intent ◽  
Salvage Regimen

Abstract Introduction There is currently no standard of care for the upfront management of patients with mature T cell non-Hodgkin lymphomas (T-NHL). The role of anthracyclines in the treatment of T-NHL remains unclear and is also associated with significant toxicity. CEPP (cyclophosphamide, etoposide, procarbazine, and prednisone), a non-anthracycline regimen, is an effective salvage regimen for relapsed/refractory NHL and has shown a favourable toxicity profile. Since 2005, CEPP has been used in Singapore in the upfront treatment of T-NHL patients either with a contraindication to anthracyclines or at physicians' discretion. Our study aimed to assess the efficacy of CEPP in the upfront treatment of T-NHL. Methods A retrospective study of all patients with newly diagnosed T-NHL treated with CEPP with curative intent from 2005-2021 was undertaken across 2 national cancer centers in Singapore. Outcomes of this population was also compared with a 1:1 control group treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) in the same time period, and matched for age, T-NHL subtype, clinical stage and international prognostic index (IPI). Patient demographics, disease characteristics and clinical outcomes (progression free survival, PFS and overall survival, OS) were evaluated. None of the patients had upfront autologous transplantation. Results We identified 34 patients treated with CEPP who met the inclusion criteria. Clinical characteristics were as follows: Median age was 71 (range 39-85), 24 (71%) were male, 26 (76%) had advanced disease (Stage III-IV) and 21 (62%) had a high intermediate or high risk IPI ( IPI 3, 14 (41%) and IPI 4-5, 21 (21%)). The most common T-NHL subtypes were peripheral T-NHL (PTCL-NOS) not otherwise specified, 11 (32%) as well as angioimmunoblastic T cell lymphoma (AITL), 16 (47%). At a median follow up of 20 months (range 2-197months), the median PFS and OS were 17.6mths and 37.2mths respectively for the CEPP group. 15/34 (44%) CEPP patients have died (8 with lymphoma, 2 from treatment toxicity and 5 from unrelated causes). In the matched control comparison, the 5yr PFS and OS were both similar for patients treated with CEPP compared to patients in the CHOP control group, PFS 30% vs 32%, p= 0.43 and OS 47% vs 52%, p = 0.32, respectively (Figure 1) Conclusion Our findings show that CEPP is a well-tolerated regimen which can cure a proportion of patients with T-NHL even without autologous transplantation consolidation. Outcome of these patients do not seem to be significantly different compared to a similar population treated with standard CHOP. This study supports CEPP as a tolerable treatment option for selected patients who cannot tolerate anthracyclines and as an alternative to CHOP regimen for older patients who are not planned for ASCT. Figure 1 Figure 1. Disclosures Jeyasekharan: Turbine Ltd: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Perkin Elmer: Other: travel funding ; MSD: Consultancy.

Increased Expression Levels Of SOX11 Correlates To Overall Survival and Adds Prognostic Value To The MIPI and MIPI-B Index In a Homogenously Treated Cohort

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4272-4272
Author(s):  
Lena Nordström ◽  
Venera Kuci ◽  
Sandra Sernbo ◽  
Kirsten Groenbaek ◽  
Arne Kolstad ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Cell Lymphoma ◽  
Risk Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
High Dose ◽  
Clinical Protocols ◽  
Ki 67 ◽  
Short Survival ◽  
Significant Difference

Abstract Introduction Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, previously correlated to a short survival of 3-5 years. Modern clinical protocols, combining immunochemotherapy, high-dose therapy and autologous stem cell transplantation (ASCT) have remarkably improved survival reaching a median survival of more than 10 years. To enable patient stratification, a MCL international prognostic index (MIPI) has been created similar to the international prognostic index (IPI) and follicular lymphoma international prognostic index (FLIPI). However, MIPI alone, or in combination with Ki-67 (MIPI-B), has shown limited use in guiding treatment decisions by poorly separating low and intermediate risk group patients treated with novel clinical protocols. The transcription factor SOX11 has during recent years been shown to be an important diagnostic, prognostic and functional antigen in MCL. We have recently developed a monoclonal antibody to target SOX11 in clinical applications such as IHC and FACS. Using this antibody with improved specificity, we investigated the prognostic use of SOX11 in the homogenously treated Nordic MCL2 and MCL3 cohort. Additionally, we investigated the prognostic value by combining SOX11 and MIPI/MIPI-B. Methods The Nordic MCL2 (n=58) and MCL3 (n=69) patient cohort, treated with first line intensive immunochemotherapy, followed by high-dose chemotherapy and ASCT as well as addition of ibritumomab radioimmunotherapy for MCL3 patients, was stained for SOX11 expression in relation to clinicopathological and biological parameters such as Ki-67, P53 and Cyclin D1. Results In total, 95 % of the Nordic MCL2/3 cohort expressed SOX11, similar to previous studies. The nuclear SOX11 stainings were classified based on both intensity and frequency; negative, weak, strong ≤ 30 % and strong > 30 %. We show that high protein levels of SOX11 (strong > 30 %) correlate to an increased survival among MCL2/3 patients (p=0.02). A positive correlation between SOX11 and Cyclin D1 (p=0.006) was identified while both P53 (p<0.001) and Ki-67 (p=0.008) showed negative correlations. More importantly, we could show that SOX11 adds prognostic value to MIPI by separating the low/intermediate MCL2/3 patient cohort into two groups with a significant difference (p=0.007) in overall survival (OS). Additionally, combining SOX11 and MIPI-B identified a large group of low risk patients with more than 10 years OS. Conclusions We show that the expression level of SOX11 correlates to improved OS in the Nordic MCL2/3 cohort, and this is the first time SOX11 has been correlated to survival in a homogenously treated cohort. Furthermore, the use of SOX11 can separate MIPI low/intermediate patients into two groups with significant difference in OS. SOX11 in combination with MIPI-B defines both a large group of patients with great outcome that benefit from the current treatment and a distinct reduced high risk group of patients with a short survival that potentially should receive alternative treatment. Thus, combining SOX11 status and the MIPI/MIPI-B can be used to stratify patients for treatment selection. Disclosures: No relevant conflicts of interest to declare.

Prognostic Significance of Ki-67 Expression in Extranodal NK/T Cell Lymphoma, Nasal Type: A Proposed Prognostic Index, KLABS Index.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2055-2055
Author(s):  
Seok Jin Kim ◽  
Soo-Young Yoon ◽  
Byung Soo Kim ◽  
Chul Won Choi ◽  
Jungwoo Choi ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Intermediate Risk ◽  
Ki 67 ◽  
Nasal Type ◽  
Nk T Cell

Abstract Ki-67 is a nuclear antigen expressed by dividing cells, therefore, the percentage of Ki-67-positive cells reflects the proportion of tumor cells actively proliferating. However, the prognostic value of Ki-67 expression is still controversial in non-Hodgkin’s lymphoma. Although a recent study in peripheral T-cell lymphoma showed a positive correlation with poor prognosis, the prognostic value of Ki-67 has never been studied in patients with extranodal NK/T cell lymphoma. Therefore, we performed this study to determine the value of Ki-67 expression in predicting prognosis and to propose a new prognostic model involving Ki-67 expression in patients with extranodal NK/T cell lymphoma. We studied 65 patients who were diagnosed with extranodal NK/T cell lymphoma from 1999 to 2005. All patients were treated with combination chemotherapy alone or followed by radiotherapy. We analyzed the percentage of Ki-67 expressing cells and determined its prognostic significance in terms of overall survival (OS) and disease-free survival (DFS). The immunohistochemical staining of Ki-67 was available for this study in fifty-five patients. The median age was 41 (range: 19 – 74 years), 89.1 percent of the patients (49/55) had an ambulatory performance status: Eastern Cooperative Oncology Group (ECOG) 0–1. Fifty-one patients presented as a localized disease: Ann Arbor stage I or II, and elevated level of serum lactate dehydrogenase (LDH) was observed in 14 patients. Thus, most patients showed the low or low-intermediate international prognostic index (IPI): low risk (74.5%, 41/55) or low intermediate risk (18.2%, 10/55). The percentage of Ki-67 expressing tumor cells was ranged from 5% to 95%, and the patients were separated into two groups: low Ki-67 (< 50%) versus high (≥ 50%). The patients in the high Ki-67 group had a shorter OS (95% CI 1.0-6.3, P = 0.046) and DFS (95% CI 1.1-5.5, P = 0.024) while the IPI failed to predict worse OS. Ki-67 expression could also predict the group with worse prognosis in 51 patients of low and low-intermediate IPI risk. Age, serum LDH, B symptoms, and tumor size were also associated with worse OS or DFS. Thus, based on the univariate and mutivariate analysis, we proposed a new prognostic index (KLABS index) with high Ki-67 expression, increased serum LDH, Age (≥ 60 years), presence of B symptoms, and bulky Size of tumors (≥ 10cm2) as follows: low risk, none or one of the above-mentioned factors; intermediate risk, presence of two factors; high risk, presence of three or more factors. This new index showed a high degree of correlation with survival outcomes in terms of OS and DFS (Figure A, B). This study demonstrated the prognostic significance of Ki-67 expression, and our new prognostic index may become a useful tool for predicting prognosis in extranodal NK/T cell lymphoma, nasal type. Figure Figure

CLINICAL SIGNIFICANCE OF SERUM CAVEOLIN-1 LEVELS IN GASTRIC CANCER PATIENTS

2018 ◽  
Vol 40 (4) ◽  
pp. 323-327 ◽  
Author(s):  
F Tas ◽  
S Karabulut ◽  
K Erturk ◽  
D Duranyildiz
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Histological Grade ◽  
Clinical Importance ◽  
Disease Stage ◽  
Control Group ◽  
Tissue Samples ◽  
Caveolin 1 ◽  
Study Results ◽  
Gastric Cancer Patients

Aim: Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. Material and Methods: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. Results: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). Conclusion: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer. Key

scholarly journals The Relationship Between Hematological Neoplasms and Lipid Profile

2021 ◽  
Author(s):  
Erman Öztürk
Keyword(s):  
Lipid Profile ◽  
Total Cholesterol ◽  
Chronic Diseases ◽  
Hematological Malignancies ◽  
Hematologic Malignancy ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Density Lipoprotein ◽  
Group Method ◽  
Control Group

Objective: Hypocholesterolemia is a metabolism disorder that may be seen in chronic diseases and malignancies. Various dyslipidemia profiles have been shown in adult and pediatric hematological malignancies. We aimed to evaluate the lipid profile properties in patients diagnosed with a hematological malignancy compared to a healthy control group. Method: Out of 1213 patients diagnosed with hematologic malignancy, the data of 98 patients whose pretreatment lipid profiles had already been studied, were reviewed. Forty healthy individuals were selected as the control group. The levels of total cholesterol, triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were compared. Results: Triglyceride values were significantly higher (p=0.02), and the total cholesterol, LDL and HDL levels were lower in the study group compared to the control group. Triglyceride values were higher (p=0.013), and HDL levels were lower (p=0.022) in parallel with increases in uric acid levels. There was a significant correlation between the International Prognostic Index (IPI) score and TG (p=0.003) in those diagnosed with non-Hodgkin lymphoma (NHL). Whereas no significant correlation was found between TG, total cholesterol, and LDL values in the limited (early) and advanced stage NHL, while a significant negative correlation was found with HDL (p=0.027). Conclusion: Hypertriglyceridemia, as well as low LDL and HDL values may be seen in hematological malignancies. It should be kept in mind that there may be chronic diseases and malignancies in the etiology of incidental hypocholesterolemia and hypertriglyceridemia. Further studies are needed on this subject to determine the effects of dyslipidemia on the pathogenesis and prognosis of the disease in hematological malignancies.

scholarly journals Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer

2018 ◽  
Vol 40 (02) ◽  
pp. 079-085 ◽  
Author(s):  
Mariana Seabra ◽  
Eduardo Cândido ◽  
Paula Vidigal ◽  
Rivia Lamaita ◽  
Angélica Rodrigues ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cervical Squamous Cell Carcinoma ◽  
Pelvic Lymphadenectomy ◽  
Histological Evaluation ◽  
Clinicopathological Parameters ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
P53 Expression ◽  
Hematoxylin And Eosin

Objective The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association. Methods Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies. Results The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix (p = 0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association between the WWOX expression with the p53 expression (p = 0.464) or the Ki-67 expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples. Conclusion The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.

scholarly journals High C-Reactive Protein to Albumin Ratio Predicts Inferior Clinical Outcomes in Extranodal Natural Killer T-Cell Lymphoma

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582091782
Author(s):  
Quan-shu Di ◽  
Tao Xu ◽  
Ying Song ◽  
Zhi-gang Zuo ◽  
Feng-jun Cao ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Natural Killer T Cell ◽  
Reactive Protein ◽  
Killer T Cell ◽  
Natural Killer T

Objective: The prognostic value of C-reactive protein to albumin ratio (CAR) has been identified in several cancers but not in extranodal natural killer T-cell lymphoma (ENKTL) as yet. We aimed to evaluate the prognostic value of CAR in ENKTL. Methods: A retrospective study with 246 patients with ENKTL was performed to determine the prognostic value of pretreatment CAR and examine the prognostic performance of CAR incorporating with International Prognostic Index (IPI) or natural killer/T-cell lymphoma prognostic index (NKPI) by nomogram. Results: The Cox regression analyses showed that high CAR (>0.3) independently predicted unfavorable progression-free survival (PFS, P = .011) and overall survival (OS, P = .012). In the stratification analysis, the CAR was able to separate patients into different prognoses regarding both OS and PFS in Ann Arbor stage I+II as well as III+IV, IPI score 0 to 1, and NKPI score 1 to 2 subgroups (all P < .05). Additionally, the predictive accuracy of the IPI-based nomogram incorporating CAR, albumin to globulin ratio (AGR), and IPI for OS and PFS appeared to be lower than the NKPI-based nomogram incorporating CAR, age, AGR, extranodal site, and NKPI. Conclusion: Pretreatment CAR is a simple and easily accessible parameter for independently predicting OS and PFS in patients with ENKTL.

scholarly journals Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma

2020 ◽  
Vol 4 (15) ◽  
pp. 3486-3494
Author(s):  
Diego Villa ◽  
Laurie H. Sehn ◽  
Kerry J. Savage ◽  
Cynthia L. Toze ◽  
Kevin Song ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
First Line ◽  
Ki 67 ◽  
Historical Cohort ◽  
Entire Cohort ◽  
Mantle Cell

Abstract Rituximab-containing chemotherapy regimens constitute standard first-line therapy for mantle cell lymphoma (MCL). Since June 2013, 190 patients ≥18 years of age with MCL in British Columbia have been treated with bendamustine and rituximab (BR). The overall response rate to BR was 88% (54% complete response). Of these, 61 of 89 patients (69%) aged ≤65 years received autologous stem cell transplantation and 141 of 190 patients (74%) from the entire cohort received maintenance rituximab. Twenty-three patients (12%) had progressive disease, associated with high risk per the Mantle Cell Lymphoma International Prognostic Index (MIPI), Ki-67 ≥50%, and blastoid/pleomorphic histology. Outcomes were compared with a historical cohort of 248 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; January 2003 to May 2013). Treatment with BR was associated with significant improvements in progression-free survival (PFS), but not overall survival (OS), compared with R-CHOP in the whole cohort (3-year PFS, 66% BR vs 51% R-CHOP, P = .003; 3-year OS, 73% BR vs 66% R-CHOP, P = .054) and in those &gt;65 years of age (3-year PFS, 56% BR vs 35% R-CHOP, P = .001; 3-year OS, 64% BR vs 55% R-CHOP, P = .063). Outcomes in transplanted patients were not statistically significantly different compared with R-CHOP (3-year PFS, 85% BR vs 76% R-CHOP, P = .135; 3-year OS, 90% BR vs 88% R-CHOP, P = .305), although in multivariate analyses, treatment with BR was associated with improved PFS (hazard ratio, 0.40 [95% confidence interval, 0.17-0.94]; P = .036) but not OS. BR is an effective first-line option for most patients with MCL, however, outcomes are suboptimal for those with high-risk features and further studies integrating novel agents are warranted.

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