scholarly journals Hepatitis B Virus Antibody as Potential Biomarker to Predict the Effect of Rituximab in Diffuse Large B-cell Lymphoma Patients

2020 ◽  
Author(s):  
Shunfeng Hu ◽  
Na Chen ◽  
Kang Lu ◽  
Changqing Zhen ◽  
Xiaohui Sui ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hbv Infection ◽  
Negative Group ◽  
Clinical Prognosis ◽  
Positive Group ◽  
Large B Cell Lymphoma ◽  
Potential Biomarker ◽  
B Virus ◽  
Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) has been correlated with virus infection and immunity status. Hepatitis B virus (HBV) infection is a significant public health problem around the world, especially in China. Previous research regarding the association of non-Hodgkin lymphoma (NHL) and HBV mostly focused on HBV antigen and HBV DNA. This study aimed to evaluate the relationship between HBV antibody and clinical prognosis in DLBCL. Methods: We retrospectively investigated the clinical characteristics of 190 newly diagnosed and untreated DLBCL patients and did a follow-up study. Results: Compared with HBeAb- patients, HBeAb+ patients displayed unique clinical features, such as more advanced disease stage (p=0.031) and higher International Prognostic Index (IPI) score (p=0.015). HBV antibody-negative patients had better therapeutic efficiency than positive patients (p<0.05). The media progression-free survival (PFS) and overall survival (OS) of HBV antibody-positive group were shorter than the negative group, respectively (p<0.05). Furthermore, we found positive association between CD21 and HBsAb (p=0.06) and their synergistic effect for prognostic predication. Interestingly, the effect of Rituximab in prognostic improvement was more significant in HBV antibody-positive group than negative group. Univariate analysis showed that HBV antibody status was independent risk factor for prognosis of DLBCL patients. Conclusions: Taken together, our investigations identified for the first time the close association between HBV antibody and clinical prognosis and Rituximab responses in DLBCL patients. These findings indicate the novel association between HBV infection and DLBCL prognosis, provide potential biomarker to predict the effect of Rituximab, and offer novel insights into the role of immune response to HBV infection in DLBCL progression.

scholarly journals The Effect of Hepatitis B Virus Antibody on Clinical Outcome and Prognosis in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4134-4134
Author(s):  
Shunfeng Hu ◽  
Na Chen ◽  
Kang Lu ◽  
Changqing Zhen ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Negative Group ◽  
Positive Group ◽  
Large B Cell Lymphoma ◽  
B Virus ◽  
The Media ◽  
Prognostic Prediction ◽  
Large B Cell

Introduction: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma (NHL), is strongly correlated with virus infection and host immunity status. To date, several kinds of virus infection have been involved in the tumorigenesis and progression of NHL, such as Epstein-Barr virus, hepatitis C virus, human immunodeficiency virus and so on. Hepatitis B virus (HBV) infection is a significant public health problem around the world, especially in China. HBV infection has been found to have an epidemiologic association with NHL and HBsAg status has been shown to be associated with the clinical feature and prognosis of DLBCL patients. However, no literature has been reported regarding the effect of HBV antibody in DLBCL. This study was to evaluate the impact of HBV antibody status on clinical outcome and prognosis in DLBCL patients. Methods: In this retrospective study, we investigated the clinical data of 190 patients with newly diagnosed and untreated DLBCL, who had received histological diagnosis and standard treatment at Shandong Provincial Hospital from May 2013 to May 2018. 127 DLBCL patients were effectively followed up to September 2018. Various statistical analyses were used to determine the significance of HBV antibody status in DLBCL patients. Results: The prevalence of HBsAg, HBsAb and HBcAb were increased in DLBCL patients compared with that in general Chinese population (Table 1).Compared with HBeAb-negative patients, HBeAb-positive patients displayed unique clinical features, such as more advanced disease stage (p=0.031) and higher International Prognostic Index (IPI) score (p=0.015, Table 2). Besides, patients in HBsAb-positive group displayed younger onset age (Figure 1). Patients in HBV antibody-negative group had better therapeutic efficiency than the positive group (Table 3), including HBsAb (p=0.013), HBeAb (p=0.013), combined HBsAb and HBcAb (p=0.019). The media progression-free survival (PFS) of HBeAb-positive group (p=0.004), HBcAb-positive group (p=0.038), HBsAb-positive and HBcAb-positive group (p=0.008) and the media overall survival (OS) of HBeAb-positive group (p=0.007), HBcAb-positive group (p=0.103), HBsAb-positive and HBcAb-positive group (p=0.035) were shorter than the negative group, respectively (Figure 2). We found the positive association between the expression of CD21 and HBsAb status (p=0.06, Table 4), both of which had no statistical significance in prognostic prediction. However, the media PFS (p=0.035) and OS (p=0.079) of patients with positive HBsAb and positive CD21 expression were worse than the negative group (Figure 3). Patients in Rituximab-containing group had better therapeutic efficiency (p=0.05), better PFS (p=0.015) and OS (p=0.008) than patients in Rituximab-free group (Figure 4). Interestingly, there were significant differences of Rituximab effect on clinical prognosis depending on the status of HBV antibody (Figure 5 and 6). For example, the positive effect of Rituximab on PFS (p=0.019) and OS (p=0.001) in HBsAb-positive patients was statistically significant while no difference was observed in PFS (p=0.251) and OS (p=0.987) in HBsAb-negative patients. In HBcAb-positive group, patients with Rituximab had better PFS (p=0.019) and OS (p=0.004) than patients without Rituximab. However, for HBcAb-negative patients, the PFS (p=0.596) and OS (p=0.80) were similar in Rituximab-containing group and Rituximab-free group. Similarly, the PFS (p=0.004 vs p=0.479) and OS (p<0.001 vs p=0.936) according to the use of Rituximab displayed significant difference in HBsAb-positive and HBcAb-positive group rather than the negative group. Conclusions: The prevalence of HBV was increased in DLBCL patients and patients with positive HBV antibody displayed unique clinical features. Our investigations identified for the first time that HBV antibody had a negative effect on clinical outcome and prognosis in DLBCL patients. Interestingly, the effect of Rituximab in prognostic prediction was more significant in HBV antibody-positive group than the negative group. Therefore, our findings lead to a novel understanding of the association between HBV antibody and DLBCL development and provide promising factors for the prognostic prediction in DLBCL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Genetic landscape of hepatitis B virus–associated diffuse large B-cell lymphoma

Blood ◽  
2018 ◽  
Vol 131 (24) ◽  
pp. 2670-2681 ◽  
Author(s):  
Weicheng Ren ◽  
Xiaofei Ye ◽  
Hong Su ◽  
Wei Li ◽  
Dongbing Liu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hbv Infection ◽  
Disease Stage ◽  
Large B Cell Lymphoma ◽  
B Virus ◽  
Large B Cell

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

scholarly journals Clinicopathological and prognostic features of hepatitis B virus-associated diffuse large B-cell lymphoma: a single-center retrospective study in China

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Dao-guang Chen ◽  
Gang Chen ◽  
Chang Wang ◽  
Long-feng Ke ◽  
Hui Wu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Advanced Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hbv Infection ◽  
Large B Cell Lymphoma ◽  
B Virus ◽  
Large B Cell

Abstract Background While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known about the pathological characteristics and outcome of DLBCL arising in patients with HBV infection. Methods We retrospectively studied a cohort of 420 patients with DLBCL for the incidence of HBV infection, and the clinicopathologic features and prognostic factors in HBsAg-positive DLBCL patients in China, a hepatitis B endemic area. Results In our study, 127 (30.2%) patients were HBsAg-positive. HBsAg-positive DLBCL displayed a younger median onset age (50 vs. 54 years, P = 0.002), more frequent involvement of the spleen (19.7% vs. 6.1%, P < 0.001), less frequent involvement of the small and large intestine (2.3% vs. 11.2%, P = 0.003), more advanced disease (stage III/IV: 56.7% vs. 45.1%, P = 0.028), and lower expression rate of MYC (49.1% vs. 66.7%, P = 0.026). The median follow-up time was 61.9 months. Univariate analysis showed that there was no significant difference in overall survival (OS) between HBsAg-negative and -positive DLBCL (P = 0.577). In the HBsAg-positive DLBCL subgroup, age older than 60 years, advanced disease, elevated lactate dehydrogenase (LDH), spleen involvement, B symptoms (fever, night sweats, weight loss), and double expressers of MYC and BCL2 had a significantly worse outcome, and patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) had a better prognosis. Multivariate analysis further confirmed that spleen involvement and rituximab use were independent prognostic factors in HBsAg-positive DLBCL patients. Conclusions Our study indicates that HBsAg-positive DLBCL has unique clinicopathological features and independent prognostic factors. Moreover, under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV-negative patients, and the use of rituximab significantly improved OS in HBsAg-positive DLBCL patients.

scholarly journals Prognostic Significance of EBV Association in Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3911-3911
Author(s):  
Nozomi Niitsu ◽  
Naoki Takahashi ◽  
Tadashi Yoshino ◽  
Masataka Okamoto ◽  
Shigeo Nakamura
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Survival Ratio ◽  
Negative Group ◽  
Positive Group ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of diseases in terms of morphology, immunohistochemistry and molecular features. The prognostic factors of DLBCL in the rituximab era are different from previously reported prognostic factors. Hans, et al. reported that patients with non-germinal center B-cell like (GCB)-type DLBCL had a significantly poorer prognosis than those with GCB-type DLBCL in the pre-rituximab era. In patients who received rituximab combination chemotherapy, there is a report that did not find a difference in survival ratio between those with GCB DLBCL or non-GCB DLBCL. On the other hand, there was a report that found a difference in survival ratio between patients with GCB DLBCL and those with non-GCB DLBCL. In addition, the previously reported that patients with Epstein-Barr virus (EBV)-positive DLBCL had a significantly poorer prognosis than those with EBV-negative DLBCL in the pre-rituximab era. In the present study, we considered the prognostic factors of DLBCL patients who received rituximab combined chemotherapy. Patients and Methods: The subjects were 209 DLBCL patients in whom immunohistochemical markers (CD20, CD5, CD10, BCL-2, BCL-6, MUM-1) could be analyzed. In addition, 86 patients were examined EBV-encoded RNA (EBER) in situ hybridization. Pathologic evaluation of the materials from each patient was performedat several central review meetings by six hematopathologists in the ALTSG pathology review board. Patients were treated with cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, and prednisolone (CyclOBEAP) regimen or CHOP regimen. Rituximab was administered to all patients. One hundred forty-six DLBCL patients who underwent CHOP-like therapy were assumed as historical controls. The median follow-up period was 69 months (range, 46-88months). Results: In the R-chemotherapy and CHOP-like groups, patients with stage III or IV disease comprised 57% and 67%, respectively, patients with performance status≧2 comprised 32% and 23%, respectively, and patients with serum LDH >normal comprised 61% and 69%, respectively. There were no significant differences in clinical characteristics between the R-chemotherapy group and CHOP-like group. BCL2 was positive in 72 (55%) of the 131 patients who received the R-chemotherapy and in 71 (50%) of the 142 patients who received the CHOP-like regimen. When the 209 patients who received the R- chemotherapy group were divided into the GCB group and the non-GCB group, the GCB group consisted of 74 patients (35%) and the non-GCB group consisted of 135 patients. The relationships between immunohistological markers and outcome among the patients with DLBCL who received CHOP-like therapy were studied. CD5, CD10, and BCL6 had no prognostic impact on 5-year overall survival (OS) and progression-free survival (PFS) rates. When the patients were divided into the GCB DLBCL and non-GCB DLBCL groups, the 5-year PFS of the GCB group was 78% and that of the non-GCB group was 48% (p=0.0008). Next, the effect of rituximab with chemotherapy was examined. CD5, CD10, BCL2, BCL6, and MUM-1 had no prognostic impact on 5-year OS and PFS rates. When the patients were divided into the GCB DLBCL (n=74) and non-GCB DLBCL (n=135) groups, the 4-year PFS of the GCB group was 79% and that of the non-GCB group was 73%, showing no significant difference. We also evaluated the significance of EBER expression among patients by incorporating the EBV-positive DLBCL (n=14) and EBV-negative DLBCL (n=72).There were no significant differences in immunophenotyping analysis between the EBV-positive DLBCL and EBV-negative DLBCL. As for EBER expression in DLBCL, the 4-year PFS of the EBER-positive group was 37% and that of the EBER-negative group was 75% (P=0.007), indicating that the EBER-positive group showed significantly poorer prognosis. The 4-year OS of the EBER-positive group was 50% and the EBER-negative group was 86% (P=0.0005). Conclusions: The EBER may be an important prognostic factor in patients with DLBCL who underwent R-chemotherapy therapy. Disclosures No relevant conflicts of interest to declare.

Prevalence and Prognostic Molecular Profiles in Hepatitis B Virus Infected Patients with Diffuse Large B Cell Lymphoma: A Retrospective Study From Chinese Population

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5211-5211
Author(s):  
Huijie Wang ◽  
Junning Cao ◽  
Xiaonan Hong
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hbv Infection ◽  
Positive Group ◽  
Large B Cell Lymphoma ◽  
Positive Expression ◽  
B Virus ◽  
Mantle Cell ◽  
Positive Rate

Abstract Abstract 5211 Introduction: Meta-analysis demonstrated that B cell lymphoma appears to be at high risk of infection by Hepatitis B Virus (HBV). Recently, cohort study showed HBV infection is associated with the increasing risk of B cell type lymphoma. Retrospective studies demonstrated high prevalence of HBV infection in Chinese lymphoma patients, with HBsAg-positive rates ranging from 23.5% to 30.5%. HBsAg-positive Diffuse Large B Cell Lymphoma (DLBCL) patients are associated with younger age and more advanced stage. However, the relation between HBV infection and poor prognosis in DLBCL remains uncertain. Molecular markers based on Immunohistochemical (IHC) expression were widely used as prognostic markers in DLBCL. Our study aimed to investigate the prevalence of HBVinfection in the different subtypes of lymphoma, and the molecular prognostic profiles in HBsAg-positive DLBCL. Patient and Methods: From Jan 2008 to Dec 2010, a total of 672 patients diagnosed as lymphoma were tested for HBsAg. Of these, 399 were male and 273 were female; 426 were B-NHL, 216 were T-NHL and 30 were HL. The expressions of BCL-2, BCL-6, CD10, MUM-1 were tested in patients diagnosed with DLBCL. Results: We found the overall HBsAg-positive rate was 15.9% (107/672) in total lymphoma patients. The positive rate of HBsAg was higher in B-NHL patients (20%,85/426) than T-NHL(9.7%,21/216) and HL (3.3%,1/30) (P<0.001).The lower prevalence were observed several subtypes of lymphoma including mantle cell lymphoma (0/20, 0%), Burkett's lymphoma (0/13, 0%), HL (1/29, 3.3%) and PTCL (4/53, 7.5%).The rate of HBV infection was higher in DLBCL patients (20.9%, 68/326). Among prognostic molecular profiles in DLBCL, the positive expression rates of BCL-2, BCL-6, CD10 and MUM-1 were 65.4% (134/205), 51.3% (116/226), 17% (39/230) and 61.5% (139/226), respectively. The non-GCB subtype accounted of 68.7% of DLBCL. Between HBsAg negative and positive group of DLBCL, the positive expression rates of BCL-2 were 64.1% vs 69.2% (P=0.498), CD 10 were 16.6% v 18.2%(P=0.781), MUM-1 were 60.5% vs 64.8%(P=0.567). However, the BCL-6 positive rate was slight higher in HBsAg negative group compared with positive group (55% vs40%, P=0.053). Finally, non-GCB subtype rates were 67.7% vs 68.7% in HBsAg negative and positive group DLBCL. Conclusion: Our date demonstrated that the infection rate of HBV was higher in DLBCL, whereas lower in the subtypes of mantle cell lymphoma, burkitt's lymphoma and HL. Based on IHC analysis, non-GCB subtype accounted of two-third of DLBCL in our series. Patients with HBsAg-positive DLBCL had lower positive rate of BCL-6. However, the expression of Bcl-2, CD10, MUM-1 seems no significant difference between patients with HBsAg-positive and negative DLBCL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Inhibitor of DNA Binding 3 Is a Potential Prognostic Biomarker in Non-GCB Diffuse Large B-Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Qunling Zhang ◽  
Jichuan Wu ◽  
Juan J. Gu ◽  
Yizhen Liu ◽  
Zuguang Xia ◽  
...  
Keyword(s):  
Dna Binding ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Negative Group ◽  
Positive Group ◽  
Large B Cell Lymphoma ◽  
Inhibitor Of Dna Binding ◽  
The Impact ◽  
Large B Cell

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. The majority of patients can be cured under the treatment of R-CHOP, but one third of patients will relapse and have a worse prognosis. To exploring a biomarker which can predict clinical behavior may aid in the implementation of novel therapeutic strategies. Inhibitor of DNA-binding 3 (ID3) is a helix loop-helix transcription factor, which negatively regulates the cell proliferation. ID3 mutations occur in 34-68% of Bukitt's lymphoma (BL) and are assiociated with lymphomagenesis. A variety of nonsense and frameshift mutations in ID3 as well as missense mutations in the region encoding the HLH domain reduces or eliminates ID3 protein function in BL. ID3 mutation is rare in DLBCL. The prognostic value of ID3 protein level remains unclear in DLBCL. Therefore, we conducted a retrospective study to investigate the impact of ID3 expression in DLBCL patients. Methods: One hundred DLBCL patients treated at Fudan University Shanghai Cancer Center with available diagnostic biopsy material were identified. ID3 expression was determined and quantified by immunohistochemistry (IHC) with staining intensity and percentage of positive cells (IRS). The IRS cut off value for ID3 positive is equal or more than 6. Kaplan-Meier and life table method were used to calculate progression free survival (PFS) and overall survival (OS). Curves were compared with the long-rank test in both groups. Correlation between the ID3 expression and clinical variables were tested by Pearson Chi Square test and a two-sided P value of &lt;0.05 was considered to be statistically significant. Result: Seventy-seven (77%) of patients was overexpressed ID3 and 23% patients was shown ID3 negative. Among these pateints, ID3 positive patients had a trend of better outcome without a significance. The PFS and OS were 65% and 68% in ID3 negative group; 80% and 85% in ID3 positive group, respectively. According to cell of origin, the ID3 deficiency were 24% (10/41) in GCB patients and 22% (13/59) in non-GCB patients (p=0.82). the ID3 overexpression was associated with a better OS compared with ID3 negative patients in non-germinal center B-cell lymphoma group (non-GCB) (85% vs 46%, p=0.047). Although the PFS of ID3 positive patients was better than negative group (77% vs 59%, p=0.256), there was no significance. In GCB patients, there was no differences between the ID3 positive group and negative groups in terms of PFS or OS. The basic characteristics were no difference between ID3 positive and negative groups. Conclusion: This is the first report demonstrating that ID3 overexpression is a positive predictor of clinical outcome in non-GCB lymphoma patients. ID3 is a potential novel target to treat lymphoma and further investigation of ID3 need to be done in the near future. (Research supported by National Natural Science Foundation of China (no.81670177, no.81001048) Figure Disclosures No relevant conflicts of interest to declare.

PKC-beta 2 Protein Expression Predicts for Poor Response to Chemotherapy and Survival in Patients with Low Risk Diffuse Large B-Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3258-3258
Author(s):  
Inigo Espinosa ◽  
Javier Briones ◽  
Ramon Bordes ◽  
Salut Brunet ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Intermediate Risk ◽  
Negative Group ◽  
Large B Cell Lymphoma ◽  
Beta 2 ◽  
Large B Cell

Abstract The protein kinase C (PKC) superfamily includes conventional PKCs (alfa, beta 1, beta 2, and gamma) and PKC-mu. PKC plays an important role in the activation and survival of B cells. Recent studies using cDNA microarrays found that PKC-beta was overexpressed in refractary diffused large B-cell lymphoma (DLBCL). The purpose of this study is to analyze the clinical significance of PKC-beta 2 protein expression in a homogeneous series of patients with DLBCL. Seventy-six patients with primary DLBCL consecutively diagnosed between 1991 and 2002 were studied. The median age of patients was 58 years (range, 11–18 years), 30 women and 46 men. Advanced stage (III/IV) was observed in 36 cases (47%). Of 71 patients with available date, 36 (50%) presented with high serum lactic acid dehydrogenase (LDH) levels. The distribution according to the International Prognostic Index (IPI) (n = 71) was as follows: low risk, 32 cases (43%); low/intermediate risk, 17 cases (23%); high/intermediate risk, 8 cases (11%); and high risk, 14 cases (19%). All patients received an anthracycline-containing chemotherapy regimen. Formalin-fixed, paraffin-embedded tissue from 76 DLBCL tumors were immunostained with a monoclonal antibody against PKC-beta 2 protein. Tumors were considered positive for PKC-beta 2 if 5% o more of the tumor cells expressed the protein. The main clinical features (B symptoms, Ann Arbor stage, bulky disease, bone marrow disease, high LDH, IPI, and ECOG) of patients within the PKC-positive group were similar to those within the PKC-negative group. Twenty-six cases (34%) were positive for PKC-beta 2 protein. Within the patients whose tumors were PKC-positive, only 8 of 26 (31%) had a complete clinical remission, while that was achieved in the majority (31 of 50; 62%) of the PKC-negative patients (p = 0.015). Patients with PKC-positive tumors had a lower five-year disease free survival (DFS) (30% vs. 60%; p = 0.03) than the PKC-beta 2 negative group. Moreover, patients with low IPI whose tumors expressed PKC-beta 2 protein had an inferior five-year DFS (39% vs. 80%; p = 0.0046). Multivariate analysis confirmed the independent adverse prognostic value of PKC expression (OR = 3.7 [95%CI, 1.4–9.9]; p = 0.007) in patients with DLBCL and low IPI. These results indicate that PKC-beta 2 expression on DLBCL predicts for a low response rate to chemotherapy and unfavorable clinical outcome, specially in those patients with low IPI.

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