Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma

Barrans, Sharon; Carter, Ian; Owen, Roger G.; Davies, Faith E.; Patmore, Russell; Haynes, Andrew; Morgan, Gareth J.; Jack, Andrew

doi:10.1182/blood.v99.4.1136

Cited by 249 publications

(242 citation statements)

References 58 publications

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“…Finally, we observed 14% of CD10 positivity suggesting a large amount of PBL of nongerminal center B-cell lymphoma (non-GCB), as shown by Yoshida et al who observed 15/ 15 non-GCB PBL [23]. Our results are therefore concordant with those that have been previously reported in PBL, as in DLBCLs [28,31,32,34,35,37] (Table III).…”

Section: Discussionsupporting

confidence: 92%

“…We found 71% of Bcl-2-positive tumor samples when more than 30% of the tumor cells were positive. This result was concordant with the 10/15 Bcl-2-positive PBL reported by Yoshiba et al [23] and the proportion of Bcl-2-positive DLBCLs reported in the literature [25][26][27][28][29][30][31][32][33][34][35][36]. Finally, we observed 14% of CD10 positivity suggesting a large amount of PBL of nongerminal center B-cell lymphoma (non-GCB), as shown by Yoshida et al who observed 15/ 15 non-GCB PBL [23].…”

Section: Discussionsupporting

confidence: 91%

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Primary breast non‐Hodgkin's lymphoma: A large single center study of initial characteristics, natural history, and prognostic factors

et al. 2009

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The aims of this study were to define the initial pathological and clinical characteristics, and prognostic factors of patients with primary breast malignant lymphoma (PBL). All patients treated at the Institut Curie for lymphoma with breast involvement were reviewed. A pathological review of all cases was performed. Fortyfive cases were selected in whom 38 cases were of diffuse large B-cell lymphoma. A complete analysis was then performed on these 38 patients. Twenty out of 28 cases (71%) of cases were Bcl-2 positive and four out of 28 (14%) had a CD10 positive staining. Peculiar initial characteristics showed nodal involvement in 58% of the cases and two or more extra-nodal sites in 31% of the cases. Among the 37 patients for whom all data were available, and according to the International Prognostic Index, 19 patients (51%) were classified in the low-risk group, 5 cases (14%) in the low-to intermediate-risk group, 6 patients (16%) in the intermediate-to high-risk group, and 7 (19%) case in the high-risk group. At the end of initial therapy, 34 patients (89%) achieved CR. With a median follow-up of 96 months, 18 patients (47%) relapsed of whom 3 had a relapse in central nervous system site. The 5-year disease-free (DFS) and overall survivals (OS) were 54% and 61%, respectively. In multivariate analysis, the presence of 2 or more extranodal sites was prognostic for lower DFS (P 5 0.0008) and OS (P 5 0.09), and a performance status ‡1 was prognostic for lower OS (P 5 0.005). Finally, when our series was compared with a historical series of 111 patients with aggressive nodal lymphomas, we observed significant lower survival rates in localized PBL (P < 0.03). Initial breast localization has a pejorative impact on the outcome of patients with Non-Hodgkin's Lymphoma (NHL), with an impressive adverse influence of additional extranodal sites. These results suggest a specific management of NHL with breast involvement. Am. J. Hematol. 84:133-139, 2009. V

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Primary breast non‐Hodgkin's lymphoma: A large single center study of initial characteristics, natural history, and prognostic factors

et al. 2009

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“…Multiple studies have looked at the expression of bcl-2 using immunostains and most have found no difference in overall survival. 16,23,[27][28][29][30][31][32][33][34][35] However, some studies have found that bcl-2 expression is associated with a significantly worse overall survival, 3,[36][37][38][39][40][41][42] or event-free survival. [29][30][31]36,37 The discrepancies related to bcl-2 expression and prognosis may be related to the underlying subgroups of DLBCL.…”

Section: Discussionmentioning

confidence: 99%

Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma

et al. 2005

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We sought to determine whether identification of poor-risk subgroups of diffuse large B-cell lymphoma (DLBCL) using immunohistochemical stains would have practical utility with regard to prognosis and therapeutic decisions. Tissue microarray blocks were created using replicate samples of formalin-fixed, paraffin-embedded tissue from 200 cases of de novo DLBCL. The sections were stained with antibodies to proteins that are expressed by activated or proliferating B cells including MUM1, FOXP1, bcl-2, survivin, protein kinase C-beta (PKC-b), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P ¼ 0.025) or PKC-b (P ¼ 0.015) was associated with a worse overall survival, whereas none of the other markers was predictive of overall survival. Patients with DLBCL that expressed either cyclin D2 or PKC-b had a 5-year overall survival of only 30% as compared to 52% for those who were negative for both markers (P ¼ 0.0019). In multivariate analysis, the expression of cyclin D2 or PKC-b was an independent predictor of poor overall survival (P ¼ 0.035). Cyclin D2 and PKC-b expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.

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“…Although numerous promising cellular targets and assays have been identified, such as p53 [9,20], p16 INK4A [21], bcl-2 [22,23], bcl-6 [23,24], and gene expression profiling [25,26], none of these have gained the level of acceptance required to be routinely used for risk stratification in trials and other clinical settings. Until such biology-based markers have been validated and standardized, clinical factors will continue to be the foundation of prognosis assessment in DLBCL.…”

Section: Discussionmentioning

confidence: 99%

Factors predicting long‐term survival in low‐risk diffuse large B‐cell lymphoma

Møller¹,

Pedersen²,

Christensen³

2003

American J Hematol

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The International Prognostic Index (IPI) is widely used for risk stratification of patients with diffuse large B-cell lymphoma (DLBCL). However, even among patients with low-risk disease, according to the IPI a substantial proportion of patients ultimately succumb to their disease. Using mature population-based data from the Danish Lymphoma Group, we analyzed if prognostic clinical pretreatment factors could be identified in patients with lowrisk DLBCL. One hundred seventy-seven patients, all with a prognostic profile as favorable as possible according to the IPI and treated with anthracycline-based combination chemotherapy (92%) or loco-regional radiotherapy/surgery (8%) with curative intent were included. The median age was 50 years and 170 achieved complete remission. The median follow-up time was 11 years. Twenty-six patients relapsed, with a median time to relapse of 12.1 months. Overall survival at 5 years and 10 years was 85% and 75%, respectively. Stage II was associated with poor response to treatment (P = 0.044). In a multivariate analysis, Stage II (P = 0.001) and age >50 years (P = 0.043) were independently associated with poor outcome. Patients without these adverse factors had an excellent prognosis, with a survival at 5 and 15 years of 90% and 80%, respectively. In contrast, patients with both adverse factors had poor outcome, with survival at 5 and 15 years of 70% and 29%, respectively (P < 0.001). The present data suggest that risk stratification of DLBCL patients with a favorable IPI score can be improved by the simple use of two clinical pretreatment factors. Am. J.

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Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma

Cited by 249 publications

References 58 publications

Primary breast non‐Hodgkin's lymphoma: A large single center study of initial characteristics, natural history, and prognostic factors

Primary breast non‐Hodgkin's lymphoma: A large single center study of initial characteristics, natural history, and prognostic factors

Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma

Factors predicting long‐term survival in low‐risk diffuse large B‐cell lymphoma

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