BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma

Kristina M. Braaten, Rebecca Betensky, Laurence De Leval, Yoshifumi Okada, Fred H. Hochberg, David N. Louis, Nancy L. Harris, Tracy T. Batchelor

Research output: Contribution to journalArticle

Abstract

Purpose: The purpose of this study was to investigate the histogenetic origin of primary central nervous system lymphoma (PCNSL) with respect to stage of B-cell differentiation and to identify prognostic markers in a cohort of patients with PCNSL treated with i.v. high-dose methotrexate therapy. Experimental Design: This study included 33 patients with PCNSL treated with high-dose i.v. methotrexate at the Massachusetts General Hospital for whom archival tumor tissue was available. All 33 patients tested negative for HIV. The lymphomas were morphologically subclassified according to the Kiel system, as modified in the WHO classification. Immunohistochemistry for the following antigens was performed: BCL-6; BCL-2; MUM1; CD10; vs38c; CD138; CD44; p16; and p53. Fluorescence in situ hybridization and multiplex PCR for CDKN2A/p16 were also performed. Results: There were 17 women and 16 men enrolled, with a median age of 60 years. All tumors were diffuse large B-cell lymphomas. Of the 23 cases that could be subclassified, 22 were centroblastic, and 1 was immunoblastic. Twenty-six of 33 tumors were BCL-6+, 6 of 32 tumors were CD10+, 27 of 29 tumors were BCL-2+, 31 of 32 tumors were MUM1+, 11 of 31 tumors were CD44+, 4 of 33 tumors were vs38c+, and 0 of 32 tumors were CD138+. There were 18 of 32 (56%) complete responses and 8 of 32 (25%) partial responses to methotrexate, whereas 6 of 33 (18%) progressed during treatment. Ten patients died of disease. Expression of BCL-6 was significantly associated with longer overall survival (P = 0.002; median survival, 101 versus 14.7 months, with approximately 95% lower confidence limits of 41.7 and 8.8 months, respectively). Conclusions: In this group of 33 patients with PCNSL, expression of BCL-6 was significantly associated with longer overall survival. BCL-6 warrants further investigation as a potentially important prognostic marker in this disease.

Original languageEnglish (US)
Pages (from-to)1063-1069
Number of pages7
JournalClinical Cancer Research
Volume9
Issue number3
StatePublished - Mar 1 2003

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Lymphoma
Central Nervous System
Survival
Neoplasms
Methotrexate
Lymphoma, Large B-Cell, Diffuse
Multiplex Polymerase Chain Reaction
Fluorescence In Situ Hybridization
General Hospitals
Cell Differentiation
B-Lymphocytes
Research Design
Immunohistochemistry
HIV
Antigens
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Braaten, K. M., Betensky, R., De Leval, L., Okada, Y., Hochberg, F. H., Louis, D. N., ... Batchelor, T. T. (2003). BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma. Clinical Cancer Research, 9(3), 1063-1069.

BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma. / Braaten, Kristina M.; Betensky, Rebecca; De Leval, Laurence; Okada, Yoshifumi; Hochberg, Fred H.; Louis, David N.; Harris, Nancy L.; Batchelor, Tracy T.

In: Clinical Cancer Research, Vol. 9, No. 3, 01.03.2003, p. 1063-1069.

Research output: Contribution to journalArticle

Braaten, KM, Betensky, R, De Leval, L, Okada, Y, Hochberg, FH, Louis, DN, Harris, NL & Batchelor, TT 2003, 'BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma', Clinical Cancer Research, vol. 9, no. 3, pp. 1063-1069.
Braaten KM, Betensky R, De Leval L, Okada Y, Hochberg FH, Louis DN et al. BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma. Clinical Cancer Research. 2003 Mar 1;9(3):1063-1069.
Braaten, Kristina M. ; Betensky, Rebecca ; De Leval, Laurence ; Okada, Yoshifumi ; Hochberg, Fred H. ; Louis, David N. ; Harris, Nancy L. ; Batchelor, Tracy T. / BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 3. pp. 1063-1069.
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abstract = "Purpose: The purpose of this study was to investigate the histogenetic origin of primary central nervous system lymphoma (PCNSL) with respect to stage of B-cell differentiation and to identify prognostic markers in a cohort of patients with PCNSL treated with i.v. high-dose methotrexate therapy. Experimental Design: This study included 33 patients with PCNSL treated with high-dose i.v. methotrexate at the Massachusetts General Hospital for whom archival tumor tissue was available. All 33 patients tested negative for HIV. The lymphomas were morphologically subclassified according to the Kiel system, as modified in the WHO classification. Immunohistochemistry for the following antigens was performed: BCL-6; BCL-2; MUM1; CD10; vs38c; CD138; CD44; p16; and p53. Fluorescence in situ hybridization and multiplex PCR for CDKN2A/p16 were also performed. Results: There were 17 women and 16 men enrolled, with a median age of 60 years. All tumors were diffuse large B-cell lymphomas. Of the 23 cases that could be subclassified, 22 were centroblastic, and 1 was immunoblastic. Twenty-six of 33 tumors were BCL-6+, 6 of 32 tumors were CD10+, 27 of 29 tumors were BCL-2+, 31 of 32 tumors were MUM1+, 11 of 31 tumors were CD44+, 4 of 33 tumors were vs38c+, and 0 of 32 tumors were CD138+. There were 18 of 32 (56{\%}) complete responses and 8 of 32 (25{\%}) partial responses to methotrexate, whereas 6 of 33 (18{\%}) progressed during treatment. Ten patients died of disease. Expression of BCL-6 was significantly associated with longer overall survival (P = 0.002; median survival, 101 versus 14.7 months, with approximately 95{\%} lower confidence limits of 41.7 and 8.8 months, respectively). Conclusions: In this group of 33 patients with PCNSL, expression of BCL-6 was significantly associated with longer overall survival. BCL-6 warrants further investigation as a potentially important prognostic marker in this disease.",
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AU - Braaten, Kristina M.

AU - Betensky, Rebecca

AU - De Leval, Laurence

AU - Okada, Yoshifumi

AU - Hochberg, Fred H.

AU - Louis, David N.

AU - Harris, Nancy L.

AU - Batchelor, Tracy T.

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N2 - Purpose: The purpose of this study was to investigate the histogenetic origin of primary central nervous system lymphoma (PCNSL) with respect to stage of B-cell differentiation and to identify prognostic markers in a cohort of patients with PCNSL treated with i.v. high-dose methotrexate therapy. Experimental Design: This study included 33 patients with PCNSL treated with high-dose i.v. methotrexate at the Massachusetts General Hospital for whom archival tumor tissue was available. All 33 patients tested negative for HIV. The lymphomas were morphologically subclassified according to the Kiel system, as modified in the WHO classification. Immunohistochemistry for the following antigens was performed: BCL-6; BCL-2; MUM1; CD10; vs38c; CD138; CD44; p16; and p53. Fluorescence in situ hybridization and multiplex PCR for CDKN2A/p16 were also performed. Results: There were 17 women and 16 men enrolled, with a median age of 60 years. All tumors were diffuse large B-cell lymphomas. Of the 23 cases that could be subclassified, 22 were centroblastic, and 1 was immunoblastic. Twenty-six of 33 tumors were BCL-6+, 6 of 32 tumors were CD10+, 27 of 29 tumors were BCL-2+, 31 of 32 tumors were MUM1+, 11 of 31 tumors were CD44+, 4 of 33 tumors were vs38c+, and 0 of 32 tumors were CD138+. There were 18 of 32 (56%) complete responses and 8 of 32 (25%) partial responses to methotrexate, whereas 6 of 33 (18%) progressed during treatment. Ten patients died of disease. Expression of BCL-6 was significantly associated with longer overall survival (P = 0.002; median survival, 101 versus 14.7 months, with approximately 95% lower confidence limits of 41.7 and 8.8 months, respectively). Conclusions: In this group of 33 patients with PCNSL, expression of BCL-6 was significantly associated with longer overall survival. BCL-6 warrants further investigation as a potentially important prognostic marker in this disease.

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