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Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma

Overexpression of bcl‐2 and c‐myc are defining features of double‐expressor‐lymphoma (DEL) but may also occur separately in patients with primary central nervous system lymphoma (PCNSL). Despite all progress in optimizing treatment regimen, there is lack of sufficient risk stratification models. Her...

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Autores principales: Hatzl, Stefan, Posch, Florian, Deutsch, Alexander, Beham‐Schmid, Christine, Stöger, Herbert, Greinix, Hildegard, Pichler, Martin, Neumeister, Peter, Prochazka, Katharina T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496545/
https://www.ncbi.nlm.nih.gov/pubmed/32101329
http://dx.doi.org/10.1002/hon.2727
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author Hatzl, Stefan
Posch, Florian
Deutsch, Alexander
Beham‐Schmid, Christine
Stöger, Herbert
Greinix, Hildegard
Pichler, Martin
Neumeister, Peter
Prochazka, Katharina T.
author_facet Hatzl, Stefan
Posch, Florian
Deutsch, Alexander
Beham‐Schmid, Christine
Stöger, Herbert
Greinix, Hildegard
Pichler, Martin
Neumeister, Peter
Prochazka, Katharina T.
author_sort Hatzl, Stefan
collection PubMed
description Overexpression of bcl‐2 and c‐myc are defining features of double‐expressor‐lymphoma (DEL) but may also occur separately in patients with primary central nervous system lymphoma (PCNSL). Despite all progress in optimizing treatment regimen, there is lack of sufficient risk stratification models. Here, we first describe the relationship between DEL biology, the National Comprehensive Cancer Network International Prognostic Index (NCCN‐IPI), treatment response, disease progression, and mortality in PCNSL. In this study, we determined c‐myc and bcl‐2 status immunohistochemically in samples of 48 patients with newly diagnosed PCNSL and followed these patients for a median interval of 6.2 years. Twelve, 18, and 17 patients harbored none, one, or both DEL features. Corresponding overall response rates after first‐line therapy were strongly associated with DEL biology (100%, 42%, and 44% in patients with 0, 1, or 2 DEL features). Patients with one or both DEL features had a 5‐fold and 13‐fold higher 5‐year risk of progression and/or death than patients without DEL features. These associations prevailed after adjusting for the NCCN‐IPI. DEL improved the discriminatory capability of the NCCN‐IPI (P = .0001). Furthermore, we could show that addition of DEL biology to the NCCN‐IPI significantly improved the score's discriminatory potential both toward progression‐free survival (increase in Harell's c = 0.15, P = .005) and overall survival (increase in Harell's c = 0.11, P = .029). In conclusion, DEL biology is a strong and simple‐to‐use predictor of adverse outcome in PCNSL. Addition of DEL to the NCCN‐IPI improves its prognostic potential. Disease progression from PCNSL harboring both DEL features is invariably fatal. This defines a novel PCNSL patient subset with a great unmet need for improved therapy.
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spelling pubmed-74965452020-09-25 Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma Hatzl, Stefan Posch, Florian Deutsch, Alexander Beham‐Schmid, Christine Stöger, Herbert Greinix, Hildegard Pichler, Martin Neumeister, Peter Prochazka, Katharina T. Hematol Oncol Original Research Articles Overexpression of bcl‐2 and c‐myc are defining features of double‐expressor‐lymphoma (DEL) but may also occur separately in patients with primary central nervous system lymphoma (PCNSL). Despite all progress in optimizing treatment regimen, there is lack of sufficient risk stratification models. Here, we first describe the relationship between DEL biology, the National Comprehensive Cancer Network International Prognostic Index (NCCN‐IPI), treatment response, disease progression, and mortality in PCNSL. In this study, we determined c‐myc and bcl‐2 status immunohistochemically in samples of 48 patients with newly diagnosed PCNSL and followed these patients for a median interval of 6.2 years. Twelve, 18, and 17 patients harbored none, one, or both DEL features. Corresponding overall response rates after first‐line therapy were strongly associated with DEL biology (100%, 42%, and 44% in patients with 0, 1, or 2 DEL features). Patients with one or both DEL features had a 5‐fold and 13‐fold higher 5‐year risk of progression and/or death than patients without DEL features. These associations prevailed after adjusting for the NCCN‐IPI. DEL improved the discriminatory capability of the NCCN‐IPI (P = .0001). Furthermore, we could show that addition of DEL biology to the NCCN‐IPI significantly improved the score's discriminatory potential both toward progression‐free survival (increase in Harell's c = 0.15, P = .005) and overall survival (increase in Harell's c = 0.11, P = .029). In conclusion, DEL biology is a strong and simple‐to‐use predictor of adverse outcome in PCNSL. Addition of DEL to the NCCN‐IPI improves its prognostic potential. Disease progression from PCNSL harboring both DEL features is invariably fatal. This defines a novel PCNSL patient subset with a great unmet need for improved therapy. John Wiley & Sons, Inc. 2020-03-07 2020-08 /pmc/articles/PMC7496545/ /pubmed/32101329 http://dx.doi.org/10.1002/hon.2727 Text en © 2020 The Authors. Hematological Oncology published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research Articles
Hatzl, Stefan
Posch, Florian
Deutsch, Alexander
Beham‐Schmid, Christine
Stöger, Herbert
Greinix, Hildegard
Pichler, Martin
Neumeister, Peter
Prochazka, Katharina T.
Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma
title Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma
title_full Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma
title_fullStr Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma
title_full_unstemmed Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma
title_short Immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma
title_sort immunohistochemistry for c‐myc and bcl‐2 overexpression improves risk stratification in primary central nervous system lymphoma
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496545/
https://www.ncbi.nlm.nih.gov/pubmed/32101329
http://dx.doi.org/10.1002/hon.2727
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