Prognostic significance of CXCR4 and mTOR expression in diffuse large B-cell lymphoma patients

Background: The aim of this study was to investigate the prognostic role of mammalian target of Rapamycin (mTOR) and C-X-C chemokine receptor type 4 (CXCR4) in diffuse large-B-cell lymphoma (DLBCL) patients.Patients and methods: This retrospective study was collected data from 64 de novo DLBCL patients, who received standardized R-CHOP therapy at two oncology centers. CXCR4 and mTOR expressions were assessed by immunohistochemistry.Results: Out of the 64 DLBCL patients, 40 patients were positive for CXCR4 (62.5%) and 35 patients for mTOR (54.7%) expressions. CXCR4 expression was positively correlated with mTOR expression (r = 0.7; p < .001). While mTOR expression was significantly associated with high lactate dehydrogenase level (p = .03) and number of extranodal sites one or more (p =.02), CXCR4 expression was significantly associated with high IPI score (p < .001) and ECOG PS (p = .005). Furthermore, theexpression levels of mTOR and CXCR4 were significantly associated with older ages and poor response to treatment (p = .04, <.001 and .04, .03, respectively). After a median Follow up of 22 months, mean ± SD overall survival (OS) was 65.391 ± 4.705. Kaplan–Meier analysis showed that patients positive for mTOR and CXCR4 expression had shorter DFS (p = .01 & .02) and OS (p = .02 & .04). Multivariate analysis showed that CXCR4 and mTOR positivity is an independent prognostic factor for significantly poorer DFS (p = .03, and .02 respectively) but not for OS (p = .09 and .08 respectively) in the DLBCL pateints.Conclusion: Our results indicate that the expression of CXCR4 and mTOR may be poor prognostic biomarkers in DLBCL.

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Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas

Oncotarget ◽

10.18632/oncotarget.16532 ◽

2017 ◽

Vol 8 (20) ◽

pp. 33487-33500 ◽

Cited By ~ 9

Author(s):

Naoko Tsuyama ◽

Daisuke Ennishi ◽

Masahiro Yokoyama ◽

Satoko Baba ◽

Reimi Asaka ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

De Novo ◽

Cell Lymphoma ◽

Prognostic Significance ◽

B Cell Lymphoma ◽

Cell Marker ◽

Large B Cell Lymphoma ◽

Marker Expression ◽

Large B Cell

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Effect of addition of rituximab to CHOP on survival of patients in both the GCB and non-GCB subgroups of diffuse large B-cell lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8040 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8040-8040 ◽

Cited By ~ 1

Author(s):

K. Fu ◽

K. D. Perry ◽

L. M. Smith ◽

C. P. Hans ◽

T. C. Greiner ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

De Novo ◽

Cell Lymphoma ◽

Prognostic Significance ◽

B Cell Lymphoma ◽

Rank Test ◽

Cell Of Origin ◽

Large B Cell Lymphoma ◽

Large B Cell

8040 Background: Diffuse large B-cell lymphoma (DLBCL) includes at least two prognostically important subgroups, i.e. germinal center B-cell (GCB) and activated B-cell (ABC) DLBCL, which were initially characterized by gene expression profiling and subsequently validated by immunostaining. Bcl-2 has also been identified as a prognostic indicator in the ABC subgroup. However, with the addition of rituximab (R) to standard chemotherapy, the prognostic significance of this subclassification of DLBCL is unclear. Methods: We studied 119 cases of de novo DLBCL including 70 cases treated with R-CHOP and 49 cases treated with CHOP. The cases were assigned to either the GCB or non-GCB subgroups using the methodology described by Hans et al (Blood 2004; 103:275). Characteristics of the patients were compared using the Chi-square test. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan Meier method and compared with the log-rank test. Results: The median age of the 119 patients was 67 years, ranging from 20 to 90 years, and there were 62 males and 57 females. The clinical characteristics of patients treated with CHOP versus R-CHOP, including the IPI, were comparable. R-CHOP was more effective than CHOP with improved 5-year EFS (63% vs 41%, p=0.013) and OS (78% vs 47%, p<0.001). In both patient groups treated with R-CHOP or CHOP, the GCB subgroup had a significantly better 5-year EFS and OS compared to the non-GCB subgroup (OS: 91% vs 64% for R-CHOP, p=0.0073; 67% vs 31% for CHOP, p=0.034, respectively). Additionally, both the GCB and non-GCB subgroups treated with R-CHOP had a significantly improved OS compared to their respective subgroups receiving CHOP alone (GCB, p=0.015; non-GCB, p=0.019). Bcl-2 expression was not a significant predictor in either the GCB or non-GCB subgroups treated with R-CHOP (OS, GCB: p=0.32; non-GCB: p=0.43). Conclusions: In this retrospective study, we demonstrate that subclassification based on the cell of origin continues to have prognostic significance in patients with DLBCL treated with R-CHOP. Addition of rituximab to CHOP improves the overall survival of patients with DLBCL in both the GCB and non-GCB subgroups. No significant financial relationships to disclose.

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Diffuse Large B-Cell Lymphoma: Relevance of bcl-2 Expression at a National Hospital from Lima Peru 2000–2002.

Blood ◽

10.1182/blood.v108.11.4610.4610 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4610-4610

Author(s):

Cecilia M. Egoavil R. ◽

Victor M. Delgado G. ◽

Jesus La Serna

Keyword(s):

B Cell ◽

Clinical Characteristics ◽

De Novo ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Response To Treatment ◽

Clear Trend ◽

Large B Cell Lymphoma ◽

Significant Difference ◽

Large B Cell

Abstract Diffuse large B-cell lymphoma (DLCL) exhibits heterogeneous clinical features and varies in response to treatment and prognosis. Establishment of parameters that can predict outcome could help to identify patients who may benefit from risk-adjusted therapies. Because apoptosis-related proteins may play an important role in predicting the prognosis of DLCL, the current study investigated the significance of bcl-2 expression in relation to clinical characteristics in this patients. We studied 125 patients (74/51 men/women; median age 64.17 years) consecutively diagnosed with de novo DLBCL in a single institution from Peru (HNGAI) during 3-year period (2000–2002).Morphology, and clinical characteristics were analyzed according to the primary site of the lymphoma and edge. Paraffin-embedded specimens from 88 were analyzed immunohistochemically for bcl-2 protein expression. Cases with a positive immunohistological stain in more than 20% of the tumor cells were considered positive expression. Results: Sites of the disease were: lymph node, 78 cases (62.4%); Waldeyer’s ring, 18 (14.4%); and extranodal sites, 45 (36%), including GI tract in 33 cases. 5-year overall survival (OS) was 19.7%. Log-rank analyses of survival showed significant differences between ≥60 years old and younger patients (P=0.003).bcl-2 expression was identified in 34 patients (38.6%), There was no significant difference in the OS (P=0.453) between the bcl-2+ (n=34) and bcl-2− (n=54) groups. In conclusion, bcl-2 expression appeared to be non predictive of a good OS in patients with DLCL, however, there was still a clear trend that the bcl-2+ patients died sooner than the patients with tumors that contained bcl-2− lymphoma cells. The current study show all patients as were staged or confined in a group with high or high intermediate IPI scores and could be candidates for alternative therapeutic approaches.

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Clinicopathologic features and prognostic significance of CD30 expression in de novo diffuse large B-cell lymphoma (DLBCL): results in a homogeneous series from a single institution

Biomarkers ◽

10.1080/1354750x.2019.1691656 ◽

2019 ◽

Vol 25 (1) ◽

pp. 69-75

Author(s):

María Queralt Salas ◽

Fina Climent ◽

Gustavo Tapia ◽

Eva DomingoDomènech ◽

Santiago Mercadal ◽

...

Keyword(s):

B Cell ◽

De Novo ◽

Cell Lymphoma ◽

Prognostic Significance ◽

B Cell Lymphoma ◽

Clinicopathologic Features ◽

Single Institution ◽

Large B Cell Lymphoma ◽

Large B Cell

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Prognostic significance of vascular endothelial growth factor (VEGF), VEGF receptors (VEGFR), and vascularity in diffuse large B-cell lymphoma treated with immunochemotherapy (R-CHOP)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8581 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8581-8581

Author(s):

D. Gratzinger ◽

R. Advani ◽

S. Zhao ◽

N. Talreja ◽

R. J. Tibshirani ◽

...

Keyword(s):

B Cell ◽

Cox Regression ◽

De Novo ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Significance ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

8581 Background: Diffuse large B cell lymphoma (DLBCL) cells coexpress VEGF, VEGFR1 and VEGFR2. In patients (pts) treated with CHOP chemotherapy alone, VEGFR1 predicted improved overall survival (OS) while microvessel density (MVD) predicted poorer OS; VEGF and VEGFR2 were not predictive (Lab Invest. 2008;88:38). We now assess these factors in pts treated with R-CHOP. Methods: 162 pts with de novo DLBCL treated with R-CHOP and median followup of 44 months were evaluated retrospectively with immunohistochemistry on tissue microarrays. Scoring: VEGF, VEGFR1, VEGFR2, and phosphoVEGFR2 (pVEGFR2) in lymphoma cells (categorical variable) <5%, none; 5–30%, weak; >30%, strong. MVD (continuous variable): average CD34+ microvessels/4 hpf. Statistics: univariate Cox proportional hazards regression, and multivariate Cox regression for testing independence from the International Prognostic Index (IPI) for two endpoints, OS and progression-free survival (PFS). Pearson chi-square testing for independence of variables. Results: VEGF and MVD did not correlate with OS or PFS. Pts with higher VEGFR2 (53%) had poorer OS but not PFS independent of the IPI (z=3.15, p=0.0016; 2 yr OS 100%/84%/76%). Pts with any pVEGFR2 (13%) had worse PFS independent of IPI (z=1.98, p=0.048) and a trend toward poor OS (p=0.056). VEGFR1 did not correlate with OS or PFS in the group as a whole. Since VEGFR1 and VEGFR2 expression correlate strongly (Χ2=56, p =9.8E-12) opposing associations with outcome could be masked. On subset analysis the 39% of pts with weak VEGFR2 had better OS with higher VEGFR1 (z=-1.64, p=0.016; 2 yr OS 68%/85%/92%). Conclusions: In contrast to our prior observations in CHOP treated pts, in DLBCL treated with R-CHOP MVD was not prognostically significant. The association of VEGFR1 with better OS was previously seen with CHOP alone, whereas the correlation of VEGFR2 and phosphorylated VEGFR2 with poorer OS was only seen with R-CHOP. Independent confirmation will be important, especially because multiple comparisons were made with 5 predictors and 2 endpoints tested. It is possible that VEGFR1 and VEGFR2 oppose each other functionally; future studies are indicated to address the mechanism of this effect. No significant financial relationships to disclose.

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