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Prognostic impact of C-REL expression in diffuse large B-cell lymphoma.

Curry CV, Ewton AA, Olsen RJ, Logan BR, Preti HA, Liu YC, Perkins SL, Chang CC - J Hematop (2009)

Bottom Line: In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan-Meier survival (KMS) analysis, p = 0.016, Breslow-Gehan-Wilcoxon test).In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS.However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow-Gehan-Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis.

View Article: PubMed Central - PubMed

Affiliation: Pathology, The Methodist Hospital Research Institute, The Methodist Hospital, 6565 Fannin St MS-205, Houston, TX, 77030, USA.

ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) phenotype is believed to confer a better prognosis than DLBCL with an activated B-cell (ABC) phenotype. Previous studies have suggested that nuclear factor-kappaB (NF-kappaB) activation plays an important role in the ABC subtype of DLBCL, whereas c-REL amplification is associated with the GCB subtype. Using immunohistochemical techniques, we examined 68 newly diagnosed de novo DLBCL cases (median follow-up 44 months, range 1 to 142 months) for the expression of c-REL, BCL-6, CD10, and MUM1/IRF4. Forty-four (65%) cases demonstrated positive c-REL nuclear expression. In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan-Meier survival (KMS) analysis, p = 0.016, Breslow-Gehan-Wilcoxon test). In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS. However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow-Gehan-Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis. These results suggest that c-REL nuclear expression may be a prognostic factor in DLBCL and it may improve patient risk stratification in combination with GCB/non-GCB phenotyping.

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Overall survival (OS) curves by Kaplan–Meier survival analysis. a OS curves using GCB versus non-GCB phenotypes. b Negative c-REL versus positive c-REL expression by our criteria. c Negative c-REL versus positive c-REL expression by Rodig’s criteria. d Only cases classified as GCB phenotype: negative c-REL versus positive c-REL expression
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Fig2: Overall survival (OS) curves by Kaplan–Meier survival analysis. a OS curves using GCB versus non-GCB phenotypes. b Negative c-REL versus positive c-REL expression by our criteria. c Negative c-REL versus positive c-REL expression by Rodig’s criteria. d Only cases classified as GCB phenotype: negative c-REL versus positive c-REL expression

Mentions: The GCB subgroup showed better overall survival (OS) than the non-GCB subgroup (50% cumulative survival not reach for GCB compared to 25–26 months for non-GCB, Kaplan–Meier survival analysis, p = 0.016, Breslow–Gehan–Wilcoxon test, Fig. 2a), using Chang’s classification scheme. The results were similar using Han’s scheme for defining GC and non-GC status (data not shown). Using only c-REL expression, no correlation with OS was observed (Fig. 2b). The finding of no correlation with OS remained the same when the data was analyzed using the 50% cutoff as defined by Rodig et al. [16] for c-REL expression (Fig. 2c). However, when combining c-REL nuclear expression with GCB vs. non-GCB phenotype as defined by Chang et al., cases with a GCB phenotype and negative nuclear c-REL had a better OS (only one out of nine patients died at 96 months with a median follow-up of 72 months) than cases with a GCB phenotype and positive nuclear c-REL (six out of 16 patients died at a median of 18 months, range 1 to 46 months, p = 0.045, Breslow–Gehan–Wilcoxon test (Fig. 2d)). When the GCB or non-GCB were defined using Han’s classification, the similar trend of having a better OS toward the group of patients with GCB phenotype and negative nuclear c-REL was observed, but the difference was not statistically significant (data not shown). Of noted, there was no statistically difference of IPI among c-REL positive or c-REL negative in the GCB phenotype subgroups (data not shown). Among the patients with non-GCB phenotype, c-REL expression did not impact the OS (data not shown).Fig. 2


Prognostic impact of C-REL expression in diffuse large B-cell lymphoma.

Curry CV, Ewton AA, Olsen RJ, Logan BR, Preti HA, Liu YC, Perkins SL, Chang CC - J Hematop (2009)

Overall survival (OS) curves by Kaplan–Meier survival analysis. a OS curves using GCB versus non-GCB phenotypes. b Negative c-REL versus positive c-REL expression by our criteria. c Negative c-REL versus positive c-REL expression by Rodig’s criteria. d Only cases classified as GCB phenotype: negative c-REL versus positive c-REL expression
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Related In: Results  -  Collection

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Fig2: Overall survival (OS) curves by Kaplan–Meier survival analysis. a OS curves using GCB versus non-GCB phenotypes. b Negative c-REL versus positive c-REL expression by our criteria. c Negative c-REL versus positive c-REL expression by Rodig’s criteria. d Only cases classified as GCB phenotype: negative c-REL versus positive c-REL expression
Mentions: The GCB subgroup showed better overall survival (OS) than the non-GCB subgroup (50% cumulative survival not reach for GCB compared to 25–26 months for non-GCB, Kaplan–Meier survival analysis, p = 0.016, Breslow–Gehan–Wilcoxon test, Fig. 2a), using Chang’s classification scheme. The results were similar using Han’s scheme for defining GC and non-GC status (data not shown). Using only c-REL expression, no correlation with OS was observed (Fig. 2b). The finding of no correlation with OS remained the same when the data was analyzed using the 50% cutoff as defined by Rodig et al. [16] for c-REL expression (Fig. 2c). However, when combining c-REL nuclear expression with GCB vs. non-GCB phenotype as defined by Chang et al., cases with a GCB phenotype and negative nuclear c-REL had a better OS (only one out of nine patients died at 96 months with a median follow-up of 72 months) than cases with a GCB phenotype and positive nuclear c-REL (six out of 16 patients died at a median of 18 months, range 1 to 46 months, p = 0.045, Breslow–Gehan–Wilcoxon test (Fig. 2d)). When the GCB or non-GCB were defined using Han’s classification, the similar trend of having a better OS toward the group of patients with GCB phenotype and negative nuclear c-REL was observed, but the difference was not statistically significant (data not shown). Of noted, there was no statistically difference of IPI among c-REL positive or c-REL negative in the GCB phenotype subgroups (data not shown). Among the patients with non-GCB phenotype, c-REL expression did not impact the OS (data not shown).Fig. 2

Bottom Line: In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan-Meier survival (KMS) analysis, p = 0.016, Breslow-Gehan-Wilcoxon test).In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS.However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow-Gehan-Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis.

View Article: PubMed Central - PubMed

Affiliation: Pathology, The Methodist Hospital Research Institute, The Methodist Hospital, 6565 Fannin St MS-205, Houston, TX, 77030, USA.

ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) phenotype is believed to confer a better prognosis than DLBCL with an activated B-cell (ABC) phenotype. Previous studies have suggested that nuclear factor-kappaB (NF-kappaB) activation plays an important role in the ABC subtype of DLBCL, whereas c-REL amplification is associated with the GCB subtype. Using immunohistochemical techniques, we examined 68 newly diagnosed de novo DLBCL cases (median follow-up 44 months, range 1 to 142 months) for the expression of c-REL, BCL-6, CD10, and MUM1/IRF4. Forty-four (65%) cases demonstrated positive c-REL nuclear expression. In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan-Meier survival (KMS) analysis, p = 0.016, Breslow-Gehan-Wilcoxon test). In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS. However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow-Gehan-Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis. These results suggest that c-REL nuclear expression may be a prognostic factor in DLBCL and it may improve patient risk stratification in combination with GCB/non-GCB phenotyping.

No MeSH data available.


Related in: MedlinePlus